WO2015073878A1 - Real-time satiety biofeedback - Google Patents

Abstract

Devices and methods are described herein for detecting and monitoring satiety in a subject. A satiety detection device includes a support, and one or more binding entities specific for one or more satiety factors selected from the group consisting of cholecystokinin (CCK), melatonin, proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin-concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon-like peptide 1 (GLP-1), pancreatic polypeptide (PP), and oxyntomodulin (OXM). The support, which may be solid, supports the binding entities. A method includes applying a subject's bodily fluid to the satiety detection device, and observing whether a signal from the device indicates that the subject is satiated.

Description

REAL-TIME SATIETY BIOFEEDBACK RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Application No. 61/904,936, filed on November 15, 2013. The entire teachings of the above application are incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] One third of adult Americans are overweight (with a BMI between 25 and 29.9) and another third are obese (a BMI of 30 or higher), according to the National Centre for Health Statistics in Toledo, Maryland. Obesity is already costing America over $190 billion a year, which is about 21% of the amount spent on medical services, and the costs are almost certain to rise much higher. If current trends continue, the American Journal of Preventive Medicine predicts that about 42%o of the population will be obese by 2030. By then, obesity will probably cost the United States about $550 billion a year.

[0003] According to the National Institute of Mental Health (NIMH) anorexia nervosa has a higher mortality rate than any other cause of death among females ages 15-24. Eating disorders have the highest mortality - or death rate - of any psychiatric disorder. Eating disorders are on the rise in some surprising populations, such as in men, older women and young children. For example, a recent study by Harvard University estimated that 25 percent of adults with eating disorders are men, and the NIMH has reported that eating disorders in men have increased 250 percent in 10 years.

[0004] Studies have shown that human beings often cannot detect their degree of fullness, or satiety. For example, genetic defects can impair a subject's ability to detect fullness, even after consumption of a meal. The mechanisms of satiety detection may be impaired not only among those suffering from obesity and anorexia, but also amongst the general population. Hence a simple method or device for monitoring satiety is needed to help people with portion control and weight management.

[0005] There are environmental factors in the developed world (e.g., social mores, social influences, image advertising, processed foods from food

manufacturers, etc.) that have broken and/or dulled the fundamental natural mammalian ability to accurately recognize one's own satiety and one's actual physiological needs. This disconnection can result in medical conditions such as obesity and other eating disorders, which often require extensive, costly and invasive treatments.

SUMMARY OF THE INVENTION

[0006] Devices and methods for real-time monitoring of the level of

physiological satiety are described herein. These devices and methods provide immediate feedback on the level of satiety of a subject and reflect the subject's own real-time chemistry, allowing the subject to evaluate whether hunger is really a physiological state of non-satiety directly related to actual low calorie-intake or whether a sensation of hunger is driven by non-physiological triggers (pleasant cooking odors or sight), external cues (e.g., food advertising) and various emotional states (e.g., depression, anxiety, boredom, etc.). Thus, a subject can quickly determine whether or not he or she is truly physiologically satiated before, during or after consuming food, i.e., whether the subject has already consumed enough food to satisfy his or her physiological needs, or whether the subject should begin or continue eating to be nourished. The devices and methods described herein can include features for recording and displaying satiety test results over time so that the user (subject) can better recognize what physiological sensations actually reflect true physiological hunger. These devices and methods described herein are unique to the consumer community. By retraining users to know when they should actually ingest food, the devices and methods described herein provide subjects with greater control over their eating patterns, and retrain subjects to properly recognize physiological satiety.

[0007] Embodiments of satiety detection devices and methods described herein have many advantages. For example, a simple, relatively non-invasive device that can immediately and accurately identify the level of a subject's physiological satiation can help to reestablish the natural mind-body connection in a user by enabling proper signaling of satiety before, during, and/or after food consumption. Further, a simple device that an individual can use frequently, on their own, and without the need for blood sampling can be a revolutionary aid in the process of enabling people to reestablish their innate mind-body connection between the perception of satiety and actual physiological fullness, thereby restoring proper nutrition, food portion control and weight management.

[0008] One aspect of the invention is a satiety detection device comprising a support, and one or more binding entities specific for one or more satiety factors selected from: cholecystokinin (CCK), melatonin, proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin-concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon-like peptide 1 (GLP-1), pancreatic polypeptide (PP), and oxyntomodulin (OXM). The support, which may be solid, supports the binding entities. The device can be used to measure the amount and/or type of satiety factor(s) in a bodily fluid sample, such as saliva, mucus, urine, gastric fluid, blood, serum, and mixtures thereof. In some embodiments, the sample is saliva. Preferred devices measure the amount and/or type of satiety factor(s) in a saliva sample, and have an easily interpreted signal or readout showing the level of physiological satiety detected.

[0009] Another aspect of the invention is a method that involves: (a) applying a subject's bodily fluid to a satiety detection device, and (b) observing whether a signal from the device indicates that the subject is satiated; wherein the device comprises a support, and one or more types of binding entities specific for a satiety factor. The methods can be used to measure the amount and/or type of satiety factor(s) in a bodily fluid sample, such as saliva, mucus, urine, gastric fluid, blood, serum, and mixtures thereof. In some embodiments, the sample is saliva.

[0010] The satiety detection device and/or method of using such a device can provide a signal or readout specifying the level of satiety as a quantitative (e.g., a percentage) or qualitative (e.g., different colors) measurement of satiety. The satiety detection device can include a signal amplifier, wireless transmitter, Bluetooth component, a wired connection to a signal receiver, signal recorder, signal processor, or a combination thereof. For example, the readout can be received, stored, and/or displayed by a smart device. A signal from the satiety detection device can be received or obtained by a smart device, for example, as a wireless signal, an electrical signal, a radio signal, a visual signal, or a photographic signal. For example, a smart device such as a cell phone can be used to photograph the signal produced on a satiety detection device. The photographed and other signals can be displayed, stored, and/or processed by the smart device. The signals can be stored over time and displayed in the form of a graph illustrating the frequency of testing, the time of day of testing, and the satiety levels detected.

[0011] The satiety detection devices and methods described herein can include a step of testing and recording the test results (signal shown on the device) over time. The satiety detection device, or a smart device operably linked to the satiety detection device, can display the subject's measured satiety levels over time, for example, as a graph, or as a display showing the signal provided by the device over time. The subject can train himself or herself to recognize actual physiological hunger, and ignore feelings of hunger when caloric intake is not needed.

[0012] At least one of the binding entities employed in a satiety detection device can have a label, or at least one of the binding entities can bind to a labeled entity, and where the label can emit the signal when the binding entity and the satiety factor form a complex. Alternatively, the formation of a complex between a binding entity and a satiety factor can provide a light signal, an electrical signal, a radio signal, a photographic signal, or other visible signal that provides a readout directly reflecting the level of physiological satiety. Such a signal can also be converted into a readout specifying the level of satiety in quantitative or qualitative form. Such devices and methods can therefore provide an absolute or graded measure of physiological satiety or fullness.

[0013] Another aspect of the invention is a kit. The kits are generally small with any of the satiety detection devices described herein, as well as instructions for using the devices and other components provided in the kits. Simple instructions are preferred where the sample application is room temperature or at physiological temperatures; the sample incubation in the device is fast and at room temperature; and the readout is simple to understand and provided in real-time. The instructions can also instruct the user to obtain an application or program for a smart device so that the smart device can receive, display, store, interpret and/or graph the results (read-out) of the satiety detection device.

[0014] Preferred satiety detection devices measure the amount and/or type of satiety factor(s) in a saliva sample, and have an easily interpreted readout. For example, the readout can be a white or green signal indicating that the subject is not yet physiologically satiated, or a yellow signal indicating that the subject is approaching satiation but has not yet reached satiation, or a red signal indicating that the subject is physiologically satiated. The methods provided herein can include a step of photographing with a smart device a visual signal on or projected by the satiety detection device. The smart device can display, process, and/or record a photographic image or other signal provided by the satiety detection device. In addition to a visual signal, the signal provided by the satiety detection devices can be an electrical or radio signal. Such electrical or radio signals can be transmitted to a receiver or detector of the signal (e.g., a smart device, a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, RFID detector, a Bluetooth, or any combination thereof), which can receive, display, store, process, and/or record the results.

[0015] By self-monitoring their satiety levels, subjects can exhibit greater control over their eating habits and develop more self-confidence about their food consumption choices.

BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The foregoing will be apparent from the following more particular description of example embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments of the present invention.

[0017] FIG. 1A-1F are schematic drawings of satiety detection devices for monitoring biological satiety. FIG. 1 A is a schematic drawing of a lateral flow satiety detection device for monitoring biological satiety. FIG. IB is a schematic drawing of a lateral flow satiety detection device illustrating display of a signal (*****) after testing the biological satiety of a subject's bodily fluid. FIG. 1C is a schematic drawing of a satiety detection device including an electrical direct-charge transfer conductometric biosensor with two electrodes, for example electrical conducting nanowires. FIG. ID is a schematic drawing of the satiety detection device shown in FIG. 1C illustrating direct charge transfer (*****) between the two electrodes, such as electrical conducting nanowires, after testing the biological satiety of a subject's bodily fluid. FIG. IE is a schematic drawing of a satiety detection device with a longer and a shorter nanowire. FIG. IF is a schematic drawing of a satiety detection device a longer and a shorter nanowire illustrating that a signal (*****) can be transmitted along a nanowire to a transmitter after testing the biological satiety of a subject's bodily fluid.

[0018] FIG. 2 illustrates a method of using a test strip for monitoring biological satiety.

[0019] FIG. 3 illustrates application of one of the satiety detection devices described herein to the tongue of a subject, so that the device can detect one or more satiety factors in the saliva of the subject.

[0020] FIGs. 4A-4G illustrate use of satiety detection devices with a smart device (e.g., a smart phone). FIG. 4A illustrates a front view of a smart device with potential connection sites for satiety detection devices. FIG. 4B illustrates a partial interior view of a smart device illustrating some of the hardware that can be present. FIG. 4C illustrates one example of a connection plug that can be connected to a smart device so that a signals from a satiety detection device can be communicated to a smart device. The connection plug can have other configurations, for example, the connection plug can be a USB plug. Alternatively, instead of a connection plug, the smart device can receive wireless signals from the satiety detection device. FIG. 4D illustrates a satiety detection device linked to a connection plug via a cable. FIG. 4E illustrates a side view of a satiety detection device with a backing and a connection plug for linkage to a smart device. FIG. 4F is an illustration of a flowchart of one embodiment of the graphical display method. FIG. 4G is a schematic diagram of an example of a computer system. DETAILED DESCRIPTION OF THE INVENTION

[0021] A description of example embodiments of the invention follows.

[0022] Satiety detection devices and methods are described herein for monitoring satiety. The satiety detection devices and methods are simple to use and provide immediate feedback on whether a subject has consumed sufficient food (and whether the subject should cease or increase further consumption of food), or whether a subject should begin or continue consuming food. The satiety detection devices and methods can be configured to include a signal transmitter so that a qualitative or quantitative signal of physiological satiety detected by satiety detection device can be received by a smart device. Alternatively, the methods described herein can include a step of simply viewing the results on the device, or photographing the results (e.g., a signal) displayed by the satiety detection device(s) by a smart device. Such a smart device can display, record and/or process the results.

[0023] As used herein "satiety" means that food intake should be curtailed because the physiological needs (e.g., caloric needs) of a mammalian subject have been met. When an individual is not satiated, food consumption can be increased. Satiety factors are secreted in a satiated mammalian subject, and the presence of such satiety factors in the subject's bodily fluids indicates that the subject is in a satiated physiological state. The amount of such satiety factors in a subject's bodily fluids correlates with the extent of physiological satiation of the subject.

Satiety Factors

[0024] As described herein, satiety factors can be detected in bodily fluids as biofeedback indicators of whether a subject has consumed sufficient food. Examples of such satiety factors include cholecystokinin (CCK), melatonin,

proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin-concentrating hormone, neurotensin, agouti -related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP), oxyntomodulin (OXM), or a combination thereof.

[0025] Cholecystokinins include CCK-33, a neuropeptide of thirty-three amino acids in its originally isolated form (see, Mutt and Jorpes, Biochem. J. 125, 678 (1971)), its carboxyl terminal octapeptide, CCK-8 (also a naturally-occurring neuropeptide and the minimum fully active sequence), and 39- and 12-amino acid forms. Gastrin occurs in 34-, 17- and 14-amino acid forms, with the minimum active sequence being the C-terminal tetrapeptide, Trp-Met-Asp-Phe-NH₂, which is the common structural element shared by both CCK and gastrin.

[0026] Research indicates that cholecystokinins are physiological satiety hormones that play a role in appetite regulation (G. P. Smith, Eating and Its

Disorders, A. J. Stunkard and E. Stellar, Eds, Raven Press, New York, 1984, p. 67), as well as stimulating colonic motility, gall bladder contraction, pancreatic enzyme secretion, and inhibiting gastric emptying. Cholecystokinin levels generally increase to a peak by about 30 minutes after eating. Accordingly, the hormone level for CCK may also be checked as an indicator of satiety.

[0027] Agouti -related protein (AGRP) is found in the hypothalamus. Obese males can have elevated levels of agouti-related protein. See, Sahu, 2004,

Endocrinology 145(6): 2613-20 (2004); Katsuki et al, J. Clin. Endocr. Metab. 86: 1921-1924 (2001), the contents of which are incorporated herein by reference in their entireties.

[0028] Bombesin or bombesin-like peptide can include a gastrin-releasing peptide or neuromedin B, which are widely distributed in the gastrointestinal tract as well as in the central nervous system. Feed suppression by bombesin or bombesin- like peptide have been reported in a variety of species including human. See

Yamamda et al., 2002, Euro. J. Pharm. 440:281-290, the contents of which are incorporated herein by reference in its entirety.

[0029] Amylin is also called islet amyloid polypeptide. Amylin is a 37 amino acid peptide that is released by the β cells of the pancreas. Research indicates that administration of amylin (or pramlintide, a synthetic human amylin analogue) can lead to decreased food intake and sustained weigh loss. See Reda et al, Obesity Res. 10: 1087-91 (2002), the contents of which are incorporated herein by reference in their entirety. Amylin levels can increase to a peak slightly less than 30 minutes after the meal. The amount of amylin in a sample can be determined as described by Ludvik et al, Diabetes 40(12): 1615-19 (1991), the contents of which are

incorporated herein by reference in their entirety. [0030] Corticotropin-releasing hormone (CRH) is also called corticotropin- releasing factor (CRF) or corticoliberin. Corticotropin-releasing hormone is a peptide hormone and a neurotransmitter involved in the stress response. It belongs to corticotropin-releasing factor family. Some reports indicate that corticotropin- releasing hormone can reduce food intake in animals (see, Kristensen et al. Nature 393(6680):72-76 (1998), the contents of which are incorporated herein by reference in their entireties).

[0031] Ghrelin is a 28 amino acid acylated peptide produced mainly by the stomach and an endogenous ligand for the growth seretagogue receptor (GHS-Rs). See Kojima et al. Nature 402(6762):656-660 (1999), the content of which is incorporated herein by reference in its entirety. Circulating levels of ghrelin rise during fasting and after feeding. See Cummings et al, 2001, Diabetes 50: 1714-19, the content of which is incorporated herein by reference in its entirety. In rodents and persons, ghrelin has been shown to increase body weight by stimulating food intake and reducing fat oxidation. See Druce et al, 2006, Intl. J. Obesity 30:293-96; Druce et al, 2005, Intl. J. Obesity 29: 1130-36; Wren et al, 2001, Diabetes

141 :4325-28, the contents of which are incorporated herein by reference in their entirety. The amount of ghrelin can be determined as described by Druce et al., Intl. J. Obesity 29: 1130-36 (2005); Akamizu et al. J. Clin. Endodrinol. Metab. 90(l):6-9 (2005)(for acylated and deacylated ghrelin); or Tschop et al, Diabetes, 50:707-09 (2001), the contents of which are incorporated herein by reference in their entirety. Ghrelin levels can decrease within about 30 minutes after the meal.

[0032] Galanin is a neuropeptide that is widely expressed in the brain, spinal cord, and gut of mammals. Some researchers report that galanin or galanin- like peptide (GALP), can stimulate food intake in rats. See, Sahu, Endocrinology 145(6): 2613-20 (2004), Patterson et al, J. Neuroendocrinol 18(10): 742-747 (2006), the contents of which are incorporated herein by reference in their entireties.

[0033] Glucagon-like peptide-1 (7-36)-amide (GLP-1) is synthesized in the intestinal L-cells by tissue-specific post-translational processing of the glucagon precursor prepro glucagon and is released into the circulation in response to a meal. See Varndell et al, J. Histochem Cytochem, 33: 1080-6 (1985), the contents of which are incorporated herein by reference in their entirety. Peripheral administration of GLP-1 in both healthy and obese subjects can suppress hunger and reduce food intake. See Flint et al, Int. J. Obes. Relat. Metab. Disord. 25(6):781-92 (2001); Gutzwiller et al, Gut 44(l):81-86 (1999), the contents of which are incorporated herein by reference in their entireties. The amount of GLP-1 in a sample can be determined as described by Kreymann et al, Gut 2(8571): 1300-04 (1987); Verdich et al, Int. J. Obesity 25: 1206-14 (2001); or Feinle et al, Peptides 23: 1491-95 (2002), the contents of which are incorporated herein by reference in their entirety.

[0034] Leptin is a 16-kDa protein hormone that is involved in regulating energy intake and expenditure, including appetite and hunger, metabolism, and behavior. It is one of the most important adipose-derived hormones (Brennan et al. Nat. Clin Pract Endocrinol Metab 2(6): 318-327 (2006)). Leptin binds to the leptin receptor. Research indicates that leptin can decrease food intake and body weight. See, Sahu A, Endocrinology 145(6): 2613-20 (2004), the contents of which are incorporated herein by reference in their entirety.

[0035] Melanin concentrating hormone (MCH) is a cyclic neuropeptide that has a role in stimulation of feeding behavior in mammals. See, Shimada et al., Nature 396: 670-673 (1998), the contents of which are incorporated herein by reference in their entirety.

[0036] Melatonin is a hormone normally and naturally secreted by the pineal gland. Melatonin can suppress suprachiasmatic nucleus (SCN) neuronal activity, which promotes relaxation, sleep, a regulated circadian rhythm, and a reduction of stress. The circadian rhythm assists with several physiological and neurological processes in the body including the sleep-wake cycle, daytime behavior, hormone (for example, growth hormone and Cortisol stress hormone) release, and dietary consumption and satiety. Accordingly, the hormone level for melatonin may be checked as an indicator of satiety.

[0037] Proopiomelanocortin is involved in the endocrine regulation of energy homeostasis. (Maratos-Flier, E., Promotion of Eating Behavior, U.S. Patent No. 5,849,708; Inui, A., "Feeding and Body- Weight Regulation by Hypothalamic Neuropeptides-Mediation of the Actions of Leptin," Trends Neurosci. 22(2):62-67, 1999; Bushnik, T., et al, "Influence of Bombesin on Threshold for Feeding and Reward in the Rat," Acta Neurobiol. Exp. (Warsz) 59(4):295-302, 1999; Sahu, A., "Evidence Suggesting That Galanin (GAL), Melanin-Concentrating Hormone (MCH), Neurotensin (NT), Proopiomelanocotin (POMC) and Neuropeptide Y (NPY) are Targets of Leptin Signaling in the Hypothalamus," Endocrinol.

139(2):795-98, 1999). Such neuropeptides are multi-functional, binding several different receptors at different sites in the body. For example, neuropeptide Y (NPY), a 36-amino-acid peptide widely expressed in the brain is a potent appetite inducing signal molecule as well as a mitogen and a vasoconstrictor active in cardiovascular homeostasis. (Kokot, F. and R. Ficek, "Effects of Neuropeptide Y on Appetite," Miner. Electrolyte Metab. 25(4-6):303-05, 1999). Accordingly, the hormone level for proopiomelanocortin may be checked as an indicator of satiety.

[0038] Neurotensin (NT) is a 13-amino-acid neuropeptide. Researchers have reported that neurotensin can decrease food intake after central administration. See, Ohinaka et al, Peptide 25(12):2135-2138 (2004), the contents of which are incorporated herein by reference in their entirety.

[0039] Neuropeptide Y mediates its effects through binding to Yl, Y2, Y4, and Y5 G-protein-coupled receptors on the surfaces of cells of the ARC-PVN of the hypothalamus. (Naveilhan, P., et al., "Normal Feeding Behavior, Body Weight and Leptin Response Require the Neuropeptide Y Y2 Receptor," Nat. Med. 5(10): 1188- 93, 1999; King, P. J., et al, "Regulation of Neuropeptide Y Release by

Neuropeptide Y Receptor Ligands and Calcium Channel Antagonists in

Hypothalamic Slices," J. Neurochem. 73(2):641-46, 1999). Peptide YY can also bind to these receptors. In addition, Yl, Y2, Y4/PP1, Y5 and Y5/PP2/Y2 receptors for peptide YY are localized in myenteric and submuscosal nerve cell bodies, endothelial cells, and endocrine-like cells of the rat intestinal tract. (Jackerott, M., et al., "Immunocytochemical Localization of the NPY/PYY Yl Receptor in Enteric Neurons, Endothelial Cells, and Endocrine-Like Cells of the Rat Intestinal Tract," J. Histochem Cytochem. 45(12): 1643-50 (December 1997); Mannon, P. J., et al, "Peptide YY/neuropeptide Y Yl Receptor Expression in the Epithelium and Mucosal Nerves of the Human Colon," Regul. Pept. 83(1): 11-19, 1999).

Accordingly, the hormone level for neuropeptide Y and/or peptide YY may be checked as an indicator of satiety. ΡΥΎ levels can peak by about an hour after a meal. For example, the amount of PYY can be determined as described by

Batterham et al, N Eng. J. Med. 349(10):941-8 (2003); Adrian T E et al, Surgery 101(6):715-19 (1987); Savage et al, Gut 28(2): 166-70 (1987); or Fuessl et al, Klin Wochenschr 66(19): 985-89 (1988), the contents of which are incorporated herein by reference in their entirety.

[0040] Pancreatic polypeptide (PP) is a 36 amino acid peptide secreted by cells in the islets of Langerhans of the pancreas. PP production in humans functions to decrease appetite and food intake, independently of gastric emptying. Thus, PP hormone levels can be monitored to assess satiety. PP levels may increase to a first peak around 15-20 minutes after the meal with a second, albeit, significantly lower peak roughly 45-60 minutes after the meal. The amount of pancreatic polypeptide can be determined as described by Berntson et al, Peptides. 14(3):497-503 (1993); Polak et al, Lancet. l(7955):328-30 (1976); or Adrian et al, Gut 17(5):393-94 (1976); the contents of which are incorporated herein by reference in their entireties.

[0041] Oxyntomodulin (OXM) is a 37-amino acid peptide hormone produced by the oxyntic (fundic) cells of the oxyntic (fundic) mucosa. Research indicates that it can suppress appetite. OXM levels may increase to a peak as soon as 90 minutes after a meal.

Satiety Detection Devices

[0042] A satiety detection device described herein can be used to evaluate, monitor and provide feedback on a subject's own physiological satiety levels by detection of any of the satiety factors described herein within the subject's bodily fluid (e.g., within saliva). Satiety can be detected and monitored using a variety of procedures or devices as described in more detail herein. A simple device that allows the subject to quickly monitor his or her physiological satiety levels is preferred. The device is preferably small enough to be easily transported, for example, in a package that easily fits in a pocket, handbag, or briefcase. For example, a package containing a series of satiety detection devices can be about the size of a package of gum, or smaller than a package of gum. The device can, for example, be a lateral flow device, a direct-charge transfer conductometric biosensor, a radio frequency identification (RFID) device, a nanowire, a flexible test strip, dip stick, or the like.

[0043] Such devices can provide a signal, such as a specific color, a radio signal, or an electrical signal to indicate whether a bodily fluid does or does not contain satiety factors. The signal can be qualitative or quantitative. Physiological satiety can be indicated by the amount of satiety factors, or by an increased or decreased number of different satiety factors. In general, higher amounts or more numerous types of satiety factors in a bodily fluid sample indicate that the subject is physiologically satiated, while lower amounts or fewer types of satiety factors in a bodily fluid sample indicate that the subject who provided the bodily fluid sample is not physiologically satiated. However, in some instances a decreased number or a reduction in the amount of a satiety factor can indicate satiety. The degree of satiation can be detected by observing the strength of a signal, a change in color, an electrical readout, an audible signal, a radio signal, or a numerical readout. For example, a white or green signal can indicate that the subject is not yet

physiologically satiated; a yellow signal can indicate that the subject is approaching satiation but has not yet reached satiation, and a red signal can indicate that the subject is physiologically satiated. The devices can be configured to quickly receive or absorb a sample (e.g., a bodily fluid) and provide real-time readout of the degree of physiological satiety. For example, any of the devices described herein can be configured for application to the tongue of a subject so that the amount and/or type of satiety factors in the saliva of the subject are measured.

[0044] The signal can also be a Bluetooth, electrical or radio signal. Such a signal can be transmitted to a receiver or detector of the signal (e.g., a smart device such as a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, an RFID detector, or any combination thereof), which can record and/or display the results. Each satiety detection device can also have an RFID tag that can be activated when the device makes contact with a bodily fluid such as saliva.

[0045] For example, a smart device can be employed that has software for converting the measured concentration of satiety factors into a readout of satiety or fullness. Alternatively, the smart device can photographically record the signal. The smart device can store the signal from, or the image of, the satiety device so that the subject can monitor the results over time. The smart device can be programmed to interpret a photographic image of the results, or an electrical, electromagnetic or radio signal emitted from the satiety detection device.

[0046] The smart device can be networked to other receiving, computing, displaying or electrical devices. For example, the signal can be transmitted from a satiety device to, or be received by, more than one the small pocket computers, laptops, netbooks, a desktop computer, or smart phones. The signal can be transmitted from a satiety device to a selected display or computing device, and the data from the selected display or computing device can be downloaded into, recorded by, or synchronized with, another computing device. A package containing the satiety detection devices can be labeled with a quick-response (QR) code that can be detected by the smart device or that the subject can photograph with a smart device (e.g., a smart phone). The QR code can "register" the individual test devices that come in that specific test strip device package to the subject's profile (which has their cell number, email, etc.). The results from the satiety detection devices in the QR-coded package can be recorded, analyzed, and/or displayed over time. Once the subject uses a test strip/lateral device from the registered pack, the RFID tag would immediately record results from a satiety detection device, evaluate and/or input the detected satiety factor results into graphic form (e.g., into the subject's chart). The results can also be immediately sent in text or email form to the subject with any of the following instructions: stop eating, start eating, or continue to eat. The subject could immediately discard the test strip or lateral flow device once they use it because they would receive an immediate discrete text or email alerting them of the results of the device.

[0047] Satiety detection devices can also be configured to "plug-in" to a smart device. For example, signals and signal analysis can be downloaded to the smart device either by physical attachment of a satiety detection device to a smart device or by wireless signal between a satiety detection device and a smart device. By attaching the device to the smart device via the smart device's

headphone/microphone jack, a robust attachment can be achieved. Such as configuration allows the non-sensor circuitry to be moved onto the smart device, for example, allowing a smaller configuration of the satiety detection device, cost reduction, and wider adoption satiety detection to facilitate reduction in health costs not only for the user but also for health care networks. Further, in some instances, power for a satiety device (if desired) can be partially or exclusively facilitated via any input/output slot in the smart device. Similarly, input data from the satiety factor detector into the smart device can be facilitated via any input/output slot in the smart device. Such an input/output slot can be a USB, audio, headphone, microphone, or other slot. Further, results, analysis, and/or output from satiety factor detector can be processed and/or visualized on the smart device. The smart device can also include control functions that are communicated to the satiety detection device (e.g., to turn on or off the detector, to re-set the detector, to initiate testing of a sample, or recalibrate the detector). Use of slots and jacks that are uniformly employed across different smart devices (e.g., USB, audio, headphone, microphone slots) are generally preferred. The smart device can, for example, be a mobile phone into which a satiety detector can be plugged or to which the satiety detection devices can be wirelessly connected.

Lateral Flow Devices

[0048] Lateral flow devices can be employed for determining the presence and/or amount of a satiety factor in a fluid sample. Such lateral flow devices can be provided in a package that is the approximately the same size as a pack of gum or smaller. These satiety detection devices typically include a sample application area, a binding entity-analyte conjugation site, and a separate conjugate capture area that provides a signal indicating whether the analyte is present in the sample. The analyte is one or more of satiety factors, for example, any of those described herein. The binding entity-analyte conjugation site contains one or more types of binding entities or antibodies that specifically bind to one or more satiety factors.

[0049] Lateral flow devices generally move the sample in a unidirectional manner from the sample application area to the binding entity-analyte conjugation site, and then to a separate capture area where a signal can be detected if the analyte is present in the sample. The sample application area is an absorbent material that can wick the sample into the analyte conjugation site. A first type of binding entity can be present in the analyte conjugation site and can bind to analyte (if present) in a sample to form a binding entity-analyte conjugate. The binding entities in the analyte conjugation site can have a visually detectable label and are mobile (i.e., not immobilized). The mobile binding entities flow to the capture area, where a second, immobilized binding entity is present that also can bind specifically with the analyte. The immobilized binding entity can bind to a different epitope on the analyte than does the mobile (first type) of binding entity. The visually detectable labels on the mobile binding entities therefore only collect in the capture area when the analyte is present. The path of flow can continue to a downstream absorbent pad associated with the lateral flow device, which acts, at least in part, as a liquid reservoir drawing the mobile binding entities past the capture site if no analyte is present. Formation of a complex between the mobile binding entities and analyte can be detected by accumulation in the capture site as the immobilized binding entities bind to the analyte-mobile binding entities. The presence and/or amount of the analyte(s) (satiety factor(s)) can therefore be detected in a fluid sample.

[0050] The lateral flow devices can have a solid support and an absorbent layer in which the mobile binding entities are impregnated in one section and to which the immobile binding entities are attached in another section, with uniform flow of the sample from an introduction port or area through the section containing the mobile binding entities and towards the section containing the immobile binding entities. A signal bound to the mobile antibodies collects in the region of the immobilized antibodies and can be read or detected in the region of the immobilized antibodies. The device provides reproducible results from one device to the next so that the type and/or quantity of signal detected by one device can be reproducible and

substantially the same from device to the next, so long as the devices have the same structure.

[0051] FIG 1 A shows a particular embodiment in which an elongated housing 10 contains a lateral flow strip 20 that extends substantially the entire length of housing 10. Lateral flow strip 20 is divided into a sample application area 40 positioned below a sample introduction port 30, a binding entity-analyte conjugation site 50, a capture area 60, and a distal absorbent pad 70. The entity-analyte conjugation site 50 can have mobile binding entities 55 for satiety factors. The flow strip 20 can also have a backing 80. The binding entities 55 in the binding entity- analyte conjugation site 50 can be labeled mobile binding entities (such as gold- conjugated Protein A, gold-conjugated Protein G, gold-conjugated antibodies) that specifically react with one or more satiety factors. A flow path along the lateral flow strip 20 passes from the sample application area 40, through the binding entity- analyte conjugation site 50, into the capture area 60. Selected immobilized binding entities (such as a capture or anchor antibody that binds the analyte) are positioned on capture area 60. The mobile binding entities 55 can bind one or more satiety factors and the liquid flow can transport a conjugate between a mobile binding entity and a satiety factor to the capture area 60, where immobilized binding entities can capture the conjugates and concentrate the label in the capture area 60. The mobile binding entities 55 can bind to a different epitope on the analyte than the capture binding entities, so that mobile binding entities 55 without a bound satiety factor flow through the capture area 60 and are eventually collected in the distal absorbent pad 70.

[0052] The lateral flow strip 20 can also include a reaction verification or control area 90. Such a control area 90 (e.g., configured as line) can be slightly distal to the capture area 60. The reaction verification or control area 90 illustrates to a user (subject) that the test has been performed. Prior to the test being performed, the reaction verification or control area 90 is not visible. However, when the test is performed by placing a fluid sample on the sample application area 40, the reaction verification or control area 90 can become visible as the sample flows through the capture area 60 and to the distal absorbent pad 70. Thus, the lateral flow device shows whether or not it has been used. In an example, the reaction verification or control area 90 can become visible due to a chemical reacting with any component of the sample or simply due to the presence of moisture in the sample. The reaction verification or control area 90, therefore, illustrates to a user that the test has been performed regardless of the outcome of the assay performed.

[0053] Quantitative results can be ascertained based on the magnitude of the identifiable signal from the capture area 60 after application of a sample to a sample introduction port 30. For example, in FIG. IB a signal represented by a series of asterisks (*****) is present in the capture area 60. [0054] The signal can be identified by visual inspection of the satiety device, and/or the signal can be recorded and/or processed by a smart device. Such a smart device can be a small pocket computer, a laptop, a netbook, a desktop computer, or a smart phone. For example, the subject can display and/or record the results by taking a photograph of the satiety factor detection device after testing by use of a smart device. The smart device can be configured to interpret the results by detecting the type and/or strength of a signal in the capture area 60 of a satiety detection device.

[0055] The lateral flow devices can be small enough for transportation in a pocket, pocket wallet, briefcase, backpack, handbag, or purse. For example, the lateral flow devices can be about 1 to 3 inches long and about 0.25 to about 1.5 inches wide. In general, the lateral flow devices are thin, having a depth of only about 0.1 to 0.75 inches.

Direct-Charge Transfer Conductometric Biosensor

[0056] A direct-charge transfer conductometric biosensor can also be employed for detecting satiety factors. Such direct-charge transfer conductometric biosensor are similar in structure to lateral flow devices and can be provided in a package that is the approximately the same size as a pack of gum or smaller. Such a biosensor can employ immobilized binding entities to sense a satiety factor and polyaniline (emeraldine salt) as a transducer for detection. The biosensor can be configured as a sandwich immunoassay, combined with an electron charge flow aided through conductive polyaniline, to generate an electronic signal that can be recorded by a data collection system. The biosensor architecture can be similar to a lateral flow device.

[0057] Polyaniline bound to mobile antibodies can first capture the satiety factor(s), if present, to form a complex between the mobile antibodies and the satiety factor(s). The complex can flow by capillary action to a capture site in the device where a sandwich complex can form with immobilized antibodies that bind a different site on the satiety factor(s) in the complex. Satiety factor-binding entity interaction provides a direct electron charge flow to generate a resistance signal that can be observed and/or recorded. The device is easy to use, and provides fast but sensitive results. See, e.g., Pal et al, Biosens. Bioelectron. 22(9-10): 2329-36 (2007)(which is incorporated herein by reference in its entirety).

[0058] For example, electrically active polyaniline coated magnetic (EAPM) particles (e.g., nanoparticles) can be synthesized by coating the surface of gamma iron oxide cores with aniline monomers that are electrically active. The aniline monomers can be made to be electrically active, for example, by acid doping.

Binding entities are adsorbed or covalently attached to the EAPM particles. The EAPM particles combined with the mobile binding entity can be incorporated into a biosensor configured similar to a lateral flow device. Detection of satiety factors occurs by complex formation between the satiety factor(s) and the EAPM particles after capillary flow of the complex to a capture region where direct-charge transfer can occur across the EAPM particles. Thus, to form the biosensor, two or more electrodes can be screen-printed onto a solid substrate (e.g., paper, nitrocellulose or other convenient substrate), where the distance between the electrodes is sufficient to isolate each electrode from another until charge transfer occur across the EAPM particles in the capture region between the electrodes.

[0059] The surface of a solid support (e.g. a nitrocellulose membrane) can be modified by a crosslinking agent such as glutaraldehyde to immobilize a satiety factor binding entity within a capture region of the biosensor. The region (epitope) of the satiety factors bound by the immobilized satiety factor binding entities is different than the region (epitope) bound by the mobile EAPM nanoparticles. The mobile EAPM particles with any bound satiety factor(s) are drawn by capillary action to the capture region. The polyaniline acts as an electric signal transducer that signals binding between the mobile EAPM particles and the immobilized satiety factor binding entities. Such an electrical response can be measured by pulse mode measurement, which provides a quantitative measure of the amount of satiety factors bound to the capture site.

[0060] For example, FIG. 1C is a schematic diagram of a direct-charge transfer conductometric biosensor with two electrodes 65 and 67, that can transfer a charge across the EAPM particles in the capture region 60 between the electrodes. FIG. ID schematically illustrates collection of EAPM particles (*****) in the capture region 60 between the electrodes. [0061] The level of satiety can be identified by visual inspection of the satiety device and/or by the transfer of charge between the electrodes that provides an electrical signal communicating the subject's satiety or fullness. The signal can also be transmitted via a transmitter 95 to a smart device (e.g., a small pocket computer, a laptop, a netbook, a desktop computer, or a smart phone), which can receive the results and alert the subject to either stop eating or continue eating depending upon the results from the satiety detection devices. The smart device can also record the results and can have software capable of converting the measured concentration of satiety factors into a readout of satiety or fullness and can chart the subject's progress.

Radio Frequency Identification (RFID) Devices

[0062] Another satiety detection device that can be employed to detect satiety factors utilizes Radio Frequency Identification (RFID), where tags ("smart labels") provide a signal to a handheld or stationary reader. Such RFID satiety detection devices can be provided in a package that is the approximately the same size as a pack of gum or smaller. The radio frequency tags can be of various shapes, sizes and readout ranges. For example, the tags can be minute, and the satiety detection strips with the tags can be thin and flexible. For example, radio frequency identification devices can have tags on a paper or plastic strip. Such RFID tags can contain silicon chips and, in some embodiments, antennas. Passive tags require no internal power source, whereas active tags require an internal power source.

[0063] The configuration of an RFID-containing satiety detection device can be similar to a lateral flow device. For example, the RFID device can have a sample port into which a sample is loaded. Such a sample may comprise, e.g., saliva, whole blood, plasma, serum, platelets, urine, lymph, etc. The sample can flow into a binding entity-analyte conjugation site where the satiety factor(s) can bind to a mobile binding entity, to form complexes with RFID-labeled binding entities. The sample passes (e.g., by capillary flow) into an RFID capture and identification zone, in which the satiety factor-RFID complexes are immobilized, for example, by binding to an immobilized binding entity that binds to a different site on the satiety factor. The capture region is then subjected to RFID interrogation by an RFID detector. The unreacted RFID-labeled binding entities (i.e., not bound to a satiety factor) and other components of the sample pass through the RFID capture and identification zone into a radio frequency protected "waste" zone, which can have shielding to prevent RFID tags therein from being detected by the RFID detector. The detection of a particular RFID tag by the RFID detector is indicative that the satiety factor is present in the sample. See, e.g., US 20120269728 by Jen et al, which is specifically incorporated herein by reference in its entirety.

[0064] FIG. IE is a schematic diagram illustrating a satiety detection device that has RFID tags as labels on binding entities 55. The device can have a shielded binding entity-analyte conjugation site 50, and shield 75 over distal absorbent pad 70, so that collection of RFID tags in the capture area 60 can transmit a radio signal (*****, see FIG. IF) indicating that one or more satiety factors have been detected by the device.

[0065] A detector or reader can receive a passive or active tag signal. A Passive Reader Active Tag (PRAT) system has a passive reader which only receives radio signals from active tags (battery operated, transmit only). The reception range of a PRAT system reader can be adjusted from 1-2,000 feet, allowing flexibility in applications such as asset protection and supervision. The detector or reader can be a smart device.

[0066] An Active Reader Passive Tag (ARPT) system has an active reader, which transmits interrogator signals and also receives authentication replies from passive tags. An Active Reader Active Tag (ARAT) system uses active tags awoken with an interrogator signal from the active reader. A variation of this system could also use a Battery Assisted Passive (BAP) tag which acts like a passive tag but has a small battery to power the tag's return reporting signal. The detector or reader can be a smart device, which can receive radio signals via Bluetooth transmission and/or reception.

Test Strip Devices

[0067] Another device that can be used for determining the presence and/or amount of one or more satiety factors in a fluid sample is a test strip. The test strips can be provided in a roll, where a section of the roll is torn off for testing. Alternatively, the test strips can be provided in a package that is approximately the same size as a pack of gum or smaller. The test strip can have one or more types of binding entities immobilized thereon. A bodily fluid can be applied to the test strip and a signal can be detected when a satiety factor is present in the bodily fluid. To enhance the signal, the strip can optionally be placed in a development solution. The signal indicates that the sample contained one or more satiety factors.

[0068] FIG. 2 shows an example of a roll of test strips 100. The roll of test strips 100 has one or more types of immobilized binding entities 110 that can specifically bind to one or more satiety factors in a test sample. A subject can tear a test strip segment 105 from the roll of test strips 100. The test sample 115 (e.g. a bodily fluid such as saliva) can be applied anyway along the test strip segment 105. A signal 125 can be detected from the test strip when a test sample contains a satiety factor. A rinsing liquid 120 (e.g., water) can optionally be used to remove unbound materials after the sample has been applied to the test strip segment 105. The test strip segment 105 can optionally be immersed in one or more development solutions 130 that can be provided with roll of test strips 100. The signal can directly be detected or the strip can optionally be rinsed in a rinsing liquid 140 (e.g., water). The signal (e.g. a red color) indicates that satiation has occurred. In some embodiments, a different signal (e.g., a green signal) indicates that the subject is not yet satiated.

[0069] The roll test strip 100 can be elongated rectangular material wound into a roll. Segments 105 of the roll of test strips 100 are easily removed or torn from the roll without loss or changes in the detection properties of the materials that make up the roll of test strips 100. In certain examples, the roll of test strips 100 can be composed of paper, nitrocellulose, or other porous inert materials. The test strips can also be in the form of short strips (e.g., about 1 to 3 inches long), that are provided in a package that is the approximately the same size as a pack of gum or smaller.

[0070] The test strips can be flexible and readily transported as individual strips in a small package, or as a continuous roll of test strip material. The test strip can vary in width, thickness, and length. For example the test strip can be about 0.2 to about 1 inch wide. The test strip can be as thick as a piece of paper or somewhat thicker, for example, about 0.02 to about 0.5 inches thick. Individual strips can be about 1 inch to 3 inches long. A continuous roll test strip material can be of varying length, for example, a length that allows easy transportation in a pocket or handbag when rolled up.

[0071] The optional development solution(s) can contain reagents that recognize the satiety factor-binding entity complex and that provide a visually detectable signal identifying that such a complex has formed. For example, a development solution can contain a secondary antibody that binds to the satiety factor to form a complex with a binding entity immobilized on the test strip. The secondary antibody can be linked to a visually detectable label, or it can be linked to an entity that can generate a visually detectable signal upon exposure to a substrate. For example, the secondary antibody can be linked to an enzyme to produces a visually detectable signal upon exposure to a substrate for the enzyme.

[0072] Quantitative results can be ascertained based on the magnitude of the identifiable signal from the test strip segment 105 that has been treated as described above. A smart device can be used to display, record, graph, and/or interpret the results. For example, the methods described herein can include a step of

photographing the results shown in the satiety detection device using a smart device. The smart device can record, store, process, and display the results as well as graphic interpretations of the results.

Nanowire Test Strips

[0073] Another device that can be used for determining the presence and/or amount of one or more satiety factors in a fluid sample is a nanowire test strip. The nanowire test strip can have a structure that is similar to a lateral flow device, and can be provided in a package that is the approximately the same size as a pack of gum or smaller. The nanowire test strip can include a sensing nanowire having a first end and a second end and a nanowire field-effect transistor (FET), each having a first end and a second end. The first end of the sensing nanowire can be connected to the nanowire FET to form a node and the second end of the sensing nanowire can be connected to a base electrode. The first end of the nanowire FET can be connected to a source electrode, while the second end of the nanowire FET can be connected to a drain electrode. The sensing nanowire and nanowire FET can include at least one semiconductor material. [0074] For example, the first end of the sensing nanowire can be connected to the nanowire FET at an angle between about 10° and about 170°. In a further embodiment, the nanowires are fabricated on a silicon substrate, for example, on silicon oxide. The sensing nanowire and the nanowire FET can have one or more of the same dimensions (e.g., about the same height, width, aspect ratio and/or length), or the sensing nanowire and the nanowire FET can be of different dimensions (e.g., different heights, widths, aspect ratios and/or lengths).

[0075] The nanowire FET sensor can be used as a biosensor, for example, by immobilizing binding entities onto the sensing nanowire, either directly or through the use of linker molecules. In one embodiment, the immobilized binding entities are homogeneous, so that each immobilized binding entity is specific for the same target satiety factor. In another embodiment, the immobilized binding entities are heterogeneous, so that at least a first binding entity is specific for a first target satiety factor and at least a second binding entity is specific for a second target satiety factor, etc.

[0076] If a sample (e.g., saliva) includes one or more target satiety factors, the satiety factor(s) bind to the device via one or more binding entities, and a change in various electrical quantities such as current, capacitance and resistance is induced. In one embodiment, a change in the nanowire FET drain current is a readout indicating whether a binding event has occurred.

[0077] The nanowire biosensor can be used in a method for detecting the presence or absence of one or more satiety factors in a sample. Such a method can include measuring the baseline drain current (I) associated with a nanowire FET device that includes a sensing nanowire having a first end and a second end and a nanowire FET having a first end and a second end, wherein the sensing nanowire and nanowire FET each comprise at least one semiconductor material, the first end of the sensing nanowire is connected to the nanowire FET to form a node. The first end of the nanowire FET is connected to a source electrode, the second end of the nanowire FET is connected to a drain electrode, and the second end of the sensing nanowire is connected to a base electrode. The sensing nanowire is derivatized with a plurality of immobilized binding entities that are specific for the binding entities of interest. The method further comprises introducing a test sample onto the sensing nanowire and measuring the change in drain current after introduction of the sample, wherein a change in drain current is associated with binding of one or more satiety factors to the device. In a further embodiment, the first end of the sensing nanowire is connected to the nanowire FET to form a node at an angle between about 10° and 170°.

[0078] To optimally detect biomolecules with low concentration and

specifically, and to allow for single molecule resolution, the nanowire FET biosensor output signals can be amplified. One issue with extrinsic amplification is the added parasitics, which can degrade the overall performance of the device. It is desirable to bring the amplifying stage closest to the transduction front-end to boost the detection sensitivity with reduced noise contribution. The devices provided herein accomplish this goal by coupling a nanowire FET with the sensing nanowire.

[0079] Further information about nanowire biosensors can be found in

WO/2012/075445 by Chui & Shin.

Quantification

[0080] A detectable signal from a satiety detection device, for example, as a result of binding entities specifically binding to satiety factor(s) can be more intense (e.g., darker) when the satiety factor(s) is of a higher concentration or quantity in the fluid sample. In another example, the identifiable change in the capture area 60 of a lateral flow device or in a test strip segment 105 can include changing to different colors depending on how much or how many satiety factors are present. For example, a first result can cause the capture area 60 of a lateral flow device or the test strip segment 105 to change to a green color, a second result can cause the capture area 60 of a lateral flow device or a test strip segment 105 to change to a yellow color, and a third result can cause the capture area 60 of a lateral flow device or a test strip segment 105 to change to a red color.

[0081] In addition to color changes, the satiety detection devices can include detectable signals generated, for example, by electrical interactions, radio signaling, by ionic interaction, by immunological interaction, by enzymatic reaction, by lateral flow immunochromatography, or by other chemistry type reactions. [0082] In other embodiments, different satiety detection devices can be used to detect different satiety factors. Different satiety factors can indicate the degree or extent of satiety.

[0083] In another example, the satiety detection devices can include multiple result zones, for different levels of satiety and/or for different satiety factors. For example, a single lateral flow device or different test strip can be used to detect different satiety factors, where the type of satiety factor in a sample can be distinguished by the color of the detectable signal.

[0084] The satiety detection devices can provide an output code or signal that is visibly displayed directly on the devices. For example, binding entities linked to a detectable label can be selectively positioned such that a color change caused by the reaction between the binding entities and the satiety factors forms one or more symbols (e.g., letters, numbers, etc.) to form the output code. For example, prior to output of the result code the capture area 60 of a lateral flow device or the test strip segment 105 can be of a uniform color. When a quantity or concentration of satiety factor(s) is present a selected portion of a symbol or an entire symbol or symbols changes color to contrast with the surrounding. Thus, the symbols of the output code become visible in the capture area 60 of a lateral flow device or the test strip segment 105.

[0085] When the signal is an electrical signal (e.g., when the device is a direct- charge transfer conductometric biosensor, or a nanowire biosensor) or a radio signal (e.g., when the device is a radio frequency identification (RFID) device) the signal can be transmitted to a smart device such as a small pocket computer, a laptop, a netbook, a desktop computer, or a smart phone. For example, the signal can be transmitted or received via Bluetooth technology. The smart device is preferably a smart phone, small handheld computer or a small pocket computer. The smart device can have software capable of converting the electrical or radio signal into a readout of satiety or fullness. Such a smart device can record, display, and/or provide a readout of results in quantitative or qualitative form.

[0086] The devices can be configured to normalize a detected satiety factor signal against a standard. For example, the lateral flow devices, direct-charge transfer conductometric biosensors, RFID satiety detection devices, and nanowires can have a standard detection area that can contain immobilized binding entities to detect a standard factor that is secreted into the bodily fluid at a relatively constant concentration. When saliva is the test sample, the standard factor can, for example, be bovine serum albumin (BSA), mucin, thyroglobulin, or a combination thereof. When urine is the test sample, the standard factor can be creatinine. The satiety factor signal can be normalized against (e.g., divided by) the signal detected for such a standard factor to correct for sampling variations (e.g., differences in the volume of fluid absorbed into the device) or to provide another method for quantifying the amount of satiety factor(s) in a test sample. Labeled mobile binding entities for a standard factor can be included in the analyte conjugation site where they can bind to the standard factor, and a complex of such labeled mobile binding entity and the standard factor can flow to the standard detection area where they collect and provide a detectable standard signal.

[0087] In general the sample volume is determined by the absorption capacity of the sample application area. Hence the device is designed to absorb substantially the same volume of fluid from one test to the next. Instructions provided with the devices can instruct the user to apply enough fluid to saturate the sample application area and gently shake off any excess.

[0088] The devices can also be configured to provide a measure of the volume of fluid absorbed by the device. For example, the lateral flow devices, direct-charge transfer conductometric biosensors, RFID satiety detection devices, and nanowires can have one or more volume detection areas that have a similar structure to the capture area. One or more volume detection areas can be positioned between the capture area and the distal absorbent pad. The volume detection areas can have immobilized binding entities to capture any remaining satiety factor(s) that were not captured by the capture area. When excess fluid is applied to the devices, volume detection areas, or a series of volume detection areas are present to signal that the limits of detection of the capture area of the device has been exceeded. When a volume detection area signal is detected and excess fluid was not applied to the sample application area, the amount of satiety factor in the sample is high, indicating that the user should cease eating. The test can be repeated when signals are observed in one or more volume detection areas to clarify the results (e.g., to distinguish between excess sample volume and high satiety factor concentration in a sample).

Satiety Factor Devices Configured for Communication with a Smart Device

[0089] The satiety detection device can be configured for direct attachment to a smart device such as a computer (e.g., a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, or any combination thereof). Alternatively, the satiety detector can be configured to be indirectly attached to the smart device, for example, via a wireless connection, Bluetooth, photographic image, or radio signals.

[0090] One aspect of the invention is a method or device that includes obtaining a photographic image of a satiety detection device that exhibits the results of a satiety factor test. A smart device can be used not only to obtain the photograph, but also to evaluate results in the photograph, and store the photographic image as well as any evaluation of the image. For example, a smart device can include a processor that graphs the signal type, and/or signal strength of tests performed over time.

[0091] The methods and devices can record and display the subject's

physiological hunger scores over time (e.g., via graphs), allowing the subject to recognize what sensations represent actual hunger and what sensations do not.

Hence, the devices and methods described herein can retrain subjects to develop healthy eating habits.

[0092] FIG. 4F is an illustration of a flowchart of one embodiment of the graphical display method, 600, discussed above. At 610 the smart device, which may be a smart phone, may receive the satiety detection device signal or may in fact photographically record an image of the satiety detection device signal using the camera of the smart phone. At 620 the smart phone may store the satiety device signal, and/or the image of the satiety device signal from the photograph taken by the camera. At 630 the smart phone may convert the satiety device signal and/or the photographic image of the satiety device signal using well known signal to graphic conversion. At 640, the smart phone may display satiety device signal graph and/or the image of the satiety device signal graph. The display may allow a user to visualize the results over time if desired. [0093] The satiety detection device and the smart device can communicate wirelessly. However, in one aspect, the satiety detection device is configured to be plugged into a smart device, for example, via one or more cables configured to receive and transmit signals from the satiety detection device to the smart device. For example, a satiety detection device is configured to be plugged into a smart device's headphone/microphone jack. In some embodiments, the smart device is a cell phone.

[0094] Satiety factor detection devices that can be directly or indirectly coupled to a smart device include, for example, lateral flow devices, direct-charge transfer conductometric biosensor, radio frequency identification (RFID) devices, test strip devices, and nanowire test strip devices.

[0095] The combination of a satiety detector and a smart device can include a headphone/microphone plug having at least sound-out, ground, and sound-in contacts; an audio signal conditioning/rectifying circuit coupled at least to the sound-out and ground contacts; a high voltage source coupled to an output of the audio signal conditioning/rectifying circuit; a satiety detector coupled to an output of the high voltage source; a pre-amplifier coupled to an output of the satiety detector; an energy detector coupled to an output of the pre-amplifier; an impedance matcher coupled to an output of the energy detector, wherein an output of the impedance matcher is coupled to the sound-in contact of the headphone/microphone plug; or any combination thereof.

[0096] FIG. 4A-4B is a schematic diagram of a portable smart device 200, with FIG. 4A showing an outside front view and FIG. 4B showing a partial inside view. The smart device shown in FIG. 4A-4B as a smart phone, but may be any smart device, including a tablet, etc. At least some of the smart devices, in the context of this disclosure, are "portable."

[0097] The smart device shown in FIG. 4 can have main power/communications port 220 and headphone jack 230. The smart device can have a touch sensitive display screen 240, and/or user input buttons 250.

[0098] Two physical data ports are shown in FIG. 4A, a main

power/communications port 220 and headphone jack 230. While

power/communications port 220 can provide digital data channels (as compared to headphone jack 230), most currently available main power/communications ports 220 in smart devices are proprietary and can vary depending upon the manufacturer. Hence, there can be non-conformity in the configuration of such

power/communications ports amongst different smart devices. For example, APPLE^® smart devices tend to have an "iPod" connection port, ANDROID^® devices tend to have a micro/mini USB connection port, and other phones/devices employ standard USB connection ports. Accordingly, there can be variability in connection port configurations across the different smart devices. Moreover, main

power/communications ports 220 are not always designed to physically support or retain a cable that is plugged into it. For example, only a small force may be needed to dislodge a cable or satiety device that is inserted into the main

power/communications port 220.

[0099] In contrast, the headphone jack 230 is typically quite robust and can retain a device/headphone plug that is plugged into it. Moreover, headphone jack configurations are relatively common across all of the smart device vendors, having only simple standard inputs and outputs.

[00100] FIG. 4B is a schematic diagram of an "inside" view of a smart device, some hardware elements of the smart device 200, including the main

power/communications port 220, headphone jack 230, main computer processing unit (CPU) 260, display driver 270, battery power 280, A/D converter 290, camera 300, or any combination thereof. The camera 300 can be used to photograph the signal or results displayed by the satiety detection device.

[00101] FIG. 4C is a schematic diagram of an exemplary conductor plug 400, for connection of a satiety detector device 500 with a smart device 200, for example, as shown in FIG. 4D. This type of plug 400 can be a TRRS plug, for example, a small or miniature TRRS plug. The plug 400 can have other configurations; for example, the plug 400 can be a USB plug. The diagram of a the connector plug 400 shown in FIG. 4C is expanded to illustrate that the connector plug can have a section 410 for ground, a section 420 for sound in (microphone), tip 430 for sound out (right), and a section 440 for sound out (left), each separated by an insulator 450. A jacket 460 can be operably connected to a cable to establish an electrical-to-mechanical connection of the section 410 for ground, a section 420 for sound in (microphone), tip 430 for sound out (right), a section 440 for sound out (left), or a combination thereof via wires in the cable to a satiety device 500 (FIG. 4D).

[00102] When the connection plug is inserted into a smart device 200, the sound out (430, 440) sections can provide a smart device output signal to a satiety detection device 500. For example, an analog sinusoidal output signal can have (e.g., for a sound output) of up to 15 mW, which is enough to drive headphones/speakers to a high volume. Of course, some smart devices may have more or less power coming out of the respective jack. Rather than driving headphone speakers, such a smart device output signal can be used as either input instructions to the satiety detection device 500, or a an energy source for the satiety detection device 500.

[00103] Although the connection plug 400 is shown in FIG. 4, with the indicated contacts, other plugs having more or less contacts can be used. For example, a small connection plug 400 can be employed that has two contacts. A monaural plug having three contacts can be used, for example, with mono out (e.g., combining Left and Right), sound in (microphone) and ground. Connection plugs can also be employed that have four or five or more contacts.

[00104] FIG. 4E shows a side view of a satiety detection device 500, with a side view of a backing 510, where the backing 510 is directly attached to a connection plug 400. Such a configuration allows almost direct connection between a satiety detection device and a smart device. The backing 510 can be joined to a connection plug 400, or the connection plug 400 can be attached to the backing 510. The backing 510 can be configured to receive signals from the satiety detection device 500 and transmit the signals to a smart device via the connection plug 400. The backing 510 can also be configured to receive instructions or power from the smart device and communicate instructions or power to the satiety detection device 500. In some embodiments, the satiety detection device is disposable and can be replaced after use with a fresh satiety detection device. Hence, the backing 510 can be configured to securely hold a satiety detection device while in use but release the satiety detection device after use. In some embodiments, the backing is a solid support for a satiety detection device. In other words, a support for a satiety detection device can be integral with or integrated into a backing that provides connection(s) to a smart device. [00105] Optionally, the smart device and the satiety detection device can communicate via a wireless mode of communication. The satiety detection device can be configured to have a wireless transmitter that can communicate with a smart device to bypass or supplement communication via a connection plug 400. For example, the backing 510 can include a wireless transmitter, as well as hardware for signal transformation and transmission. In some embodiments, the connection plug 400 can (also) serve as an antenna to transmit signals from the backing of the satiety detection device to a smart device.

[00106] Commands, data, power and so forth may be communicated into the connection plug 400 from the smart device. The satiety detection device 500 can be operably connected to the backing to receive such commands and transmit data and information to the backing. Different amplitudes, frequencies, or signal strengths of the output from the satiety detection device can signify the amount or level of the detected satiety factor(s).

[00107] The information from the satiety detection device can be communicated to the subject user via the smart device to the subject in the form of a numerical, visual, or audible signal. For example, the smart device can communicate a percent satiety, or graphically illustrate the degree of satiety. The smart device can display a colored signal to indicate to the subject whether to continue eating (e.g., green), slow down consumption (e.g., yellow), or stop eating (e.g., red). The smart device can also signal the subject to stop or continue eating either audibly or as a written message. The smart detector can also record the amount(s) or satiety factor(s) detected over time so that the subject can keep track of his or her feedback control over time. Modifications to the configuration and type of signal forwarded to the smart device may be contemplated without departing from the spirit and scope of this disclosure.

[00108] The system of FIG. 4B may be seen in greater detail in FIG. 4G and may include an example computer system that may include a processor 260 (e.g., the central processing unit of FIG. 4B), a main memory 261 and a static memory 262, which communicate with each other via a bus 263. The computer system may further include a video display unit 264 (e.g., a liquid crystal display (LCD)). In example embodiments, the computer system also includes one or more of an alpha- numeric input device 265, a user interface (UI) navigation device or cursor control device 266, and a network interface device 267. Signal generation device 268 may be, in one example, capture area 60 of FIG. 1. Alternatively, signal generation device 268 may be operatively connected to capture area 60.

[00109] The static memory 262 may store one or more sets of instructions and data structures (e.g., software instructions) embodying or used by any one or more of the methodologies or functions described herein. The instructions may also reside, completely or at least partially, within the main memory 261 or within the processor 260 during execution thereof by the computer system, with the main memory 261 and the processor 260 also constituting machine-readable media which may be any tangible media or storage devices that may be capable of storing, encoding, or carrying instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies of embodiments of the present description, or that may be capable of storing, encoding, or carrying data structures used by or associated with such instructions. Examples may include, but not be limited to, solid-state memories and optical and magnetic media. The instructions may further be transmitted or received over a communications network 269 using a transmission medium via the network interface device 267 and utilizing any one of a number of well-known transfer protocols (e.g., Hypertext Transfer Protocol (HTTP)). Examples of communication networks include a local area network (LAN), a wide area network (WAN), the Internet, mobile telephone networks, Plain Old Telephone Service (POTS) networks, and wireless data networks (e.g., WiFi and WiMax networks).

Methods

[00110] A method is described herein for monitoring satiety in a mammalian subject. The method involves contacting a satiety detection device described above with a sample from the mammalian subject, and observing whether an identifiable signal is displayed by the device. The method can also include transmitting a signal from the satiety detection device to a receiver, or a smart device. The signal from the satiety detection device can be a photographic image, an electrical signal, a radio signal, a color, and combinations thereof. The signal received and/or displayed by the smart device can be a color signal, a photograph, a written signal, a verbal signal, a graph, or a combination thereof. In some embodiments, the method can include identifying the degree of satiation by observing a colored or a quantified signal from the device.

[00111] The sample can be a bodily fluid such as saliva, mucus, urine, gastric fluid, blood, serum, and mixtures thereof. In some embodiments, the sample is saliva. FIG. 3 illustrates application of one of the satiety detection devices described herein to the tongue of a subject 310, so that the device 305 can detect one or more satiety factors in the saliva of the subject. The device 305 may be a lateral flow device or a test strip as described herein. Also shown is package 315 that contains a series of satiety detection devices. The package can be similar in size to a package of gum.

[00112] The amount of satiety factors in bodily fluids can vary somewhat from individual to individual. Also satiety levels for some individuals can be more highly correlated with some satiety factors, but not with others. An individual may therefore secrete low or high levels of satiety factors that are less representative of that individual's actual satiety level. The method can therefore include establishing a 'non-satiated' baseline, where the subject has fasted for a specified time (e.g., in the morning after a night's sleep and before food consumption), then tests a bodily fluid, and observes what signal (if any) is observable. The subject can then note what type of signal, and how much signal is observed with the subject is not satiated. The method can also include establishing a definitive 'satiated' signal, where the subject has eaten a meal and observes what type of signal, and how much signal is observed with the subject is definitely satiated. The subject can then accurately monitor satiation levels in the future.

[00113] The satiety detection device provides real-time measurements of a user's level of physiological satiety. However, the precision of satiety measurements may be fine-tuned by using the device to establish definitive fasting and/or satiated signals. Instructions can be provided with the device for establishing non-satiated baseline and definitive 'satiated' signals. For example, the instructions can describe fasting conditions (time, etc.) for establishing a non-satiated baseline, caloric intake or a meal description for establishing a definitive 'satiated' signal, sample application to the device, use of the device (e.g., whether the device should be washed, incubated with a development solution, and/or how long a signal will take to develop), reading the signal, the significance of the signal (e.g., what type of signal indicates satiation or non-satiation), and other information.

[00114] The instructions can also specify what type of sample should be applied to the device, and how much sample is applied. The instructions can recite times for incubation of the sample in or on the device, and how quickly a readout will be provided by the device (e.g., a real-time readout). The instructions can also specify temperatures for storage, use and incubation of the device with samples. For example, the instructions can specify how the device should be stored (e.g., in the absence of moisture), and when the reagents in the device may expire or become less potent. Such instructions can be provided in a kit that also contains at least one of the devices described herein.

[00115] A medical adviser, dietician, or diet adviser can familiarize a subject with the use of the device, and help establish non-satiated baseline and definitive

'satiated' signals by working with a subject. For example, a diet adviser can advise the subject to report to a dietary center after fasting for a specified time (e.g., 4-8 hours) for initial testing. The dietary adviser can then test samples from the subject in one or more devices to establish a non-satiated baseline for those devices with that subject. The dietary adviser can then provide the subject with a meal specifically designed to provide satiation in the subject. Samples from the satiated subject can then be tested using one or more devices to establish definitive 'satiated' signals for the subject with those devices. As the dietary adviser performs these tests, the subject can observe and receive instruction on the use of the device(s). The subject can then be provided with one or more devices that can appropriately be used at home (or anywhere) during mealtime to monitor satiation.

[00116] The method can include a step where the satiety detection device, or a smart device in communication with the satiety detection device, plots and displays a graph of the results over time so that the subject can record and monitor the results, thereby training the subject to eat when he is she is actually in need of food consumptions. The satiety detection device and methods provided herein retrain the subject to eat when food intake is actually needed. Binding Entities

[00117] Each binding entity binds a satiety factor with specificity. As used herein, "binding entities" include any molecule that can specifically bind to a satiety factor. Binding entities are typically binding regions of affinity molecules available in the biological sciences including, but not limited to, antibodies, antibody fragments, leucine zippers, histones, complementary determining regions (CDRs), single chain variable fragments (scFv's), receptors, ligands, aptamers, lectins, nucleic acid probes and the like. Binding entities can include binding regions that are generated, for example, of full sized versions of an affinity molecule, fragments of an affinity molecule, or the smallest portion of the affinity molecule providing binding that is useful in the detection of a target of interest (a satiety factor).

[00118] In an embodiment, the devices include binding entities which are members of the immunoglobulin family of proteins, or derivatives thereof. For example, the binding entity can be a complete immunoglobulin or antibody, a fragment, a single chain variable fragment (scFv), a heavy or light chain variable region, a CDR peptide sequence, and/or the like.

[00119] As used herein, "antibody" refers to an immunoglobulin molecule, and fragments thereof, which are immunologically reactive with a particular antigen. The term "antibodies" refers to a plurality of such molecules and is not limited to homogeneous populations of a single type of antibody. The term "antibody" also includes genetically engineered forms such as chimeric antibodies, heteroconjugate antibodies (e.g., bispecific antibodies), and recombinant single chain Fv fragments (scFv), and disulfide stabilized (dsFv) Fv fragments (see, for example U.S. Pat. No. 5,747,654). The term "antibody" also includes antigen binding forms of antibodies (e.g., Fab', F(ab')2, Fab, Fv and rlgG. See also, Pierce Catalog and Handbook, 1994- 1995 (Pierce Chemical Co., Rockford, 111.).

[00120] Antibodies for use in the devices described herein can be obtained commercially or can be generated by available methods. Methods of making antibody fragments are available in the art (see for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York, (1988), specifically incorporated herein by reference in its entirety). For example, antibodies suitable for use in the devices can be obtained by immunizing an animal such as a rabbit, goat, sheep, horse, or guinea pig. Such antibodies are present in the blood (e.g., serum) of immunized animals.

[00121] Antibody fragments can be prepared by proteolytic hydrolysis of the antibody or by expression of nucleic acids encoding the antibody fragment in a suitable host. Antibody fragments can be obtained by pepsin or papain digestion of whole antibodies conventional methods. For example, antibody fragments can be produced by enzymatic cleavage of antibodies with pepsin to provide a 5S fragment described as F(ab')₂. This fragment can be further cleaved using a thiol reducing agent, and optionally using a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce 3.5S Fab' monovalent fragments. Alternatively, enzymatic cleavage using pepsin produces two monovalent Fab' fragments and an Fc fragment directly. These methods are described, for example, in U.S. Patents No. 4,036,945 and No. 4,331,647, and references contained therein. These patents are hereby incorporated herein by reference in their entireties.

[00122] A number of proteins can serve as protein scaffolds to which binding domains can be attached and thereby form a suitable binding entity. The binding domains bind or interact with satiety factors while the protein scaffold merely holds and stabilizes the binding domains so that they can bind. A number of protein scaffolds can be used. For example, phage capsid proteins can be used. See Review in Clackson & Wells, Trends Biotechnol. 12: 173-184 (1994). Phage capsid proteins have been used as scaffolds for displaying random peptide sequences, including bovine pancreatic trypsin inhibitor (Roberts et al, PNAS 89:2429-2433 (1992)), human growth hormone (Lowman et al., Biochemistry 30: 10832-10838 (1991)), Venturini et al, Protein Peptide Letters 1 :70-75 (1994)), and the IgG binding domain of Streptococcus (O'Neil et al, Techniques in Protein Chemistry V (Crabb, L,. ed.) pp. 517-524, Academic Press, San Diego (1994)). These scaffolds have displayed a single randomized loop or region that can be modified to include binding domains for satiety factors.

[00123] Fibronectin type III domain has also been used as a protein scaffold to serve as a binding entity platform. Fibronectin type III is part of a large subfamily (Fn3 family or s-type Ig family) of the immunoglobulin superfamily. Sequences, vectors and cloning procedures for using such a fibronectin type III domain as a protein scaffold portion of a binding entity (e.g. that includes CDR peptides) are provided, for example, in U.S. Patent Application Publication 20020019517. See also, Bork, P. & Doolittle, R. F. (1992) Proposed acquisition of an animal protein domain by bacteria. Proc. Natl. Acad. Sci. USA 89, 8990-8994; Jones, E. Y. (1993) The immunoglobulin superfamily Curr. Opinion Struct. Biol. 3, 846-852; Bork, P., Horn, L. & Sander, C. (1994) The immunoglobulin fold. Structural classification, sequence patterns and common core. J. Mol. Biol. 242, 309-320; Campbell, I. D. & Spitzfaden, C. (1994) Building proteins with fibronectin type III modules Structure 2, 233-337; Harpez, Y. & Chothia, C. (1994).

[00124] It can be useful to employ a binding entity that binds to a selected satiety factor with specificity. For example, the binding entity can have an affinity for a satiety factor of about l x lO⁷ ΜΓ¹ to about l x lO¹⁰ ΜΓ¹, or about l x lO⁸ IVT¹ to about 1 x 10⁹ M^-1. For example, the affinity of a binding entity can be measured by detecting and quantifying the formation of a binding entity-satiety factor complex, generally referred to as an antigen-antibody complex [Ag-Ab]. The formation of such an antigen-antibody complex [Ag-Ab] is illustrated by the following reaction.

Ab + Ag ^^ AbAg

The formation of such an Ag-Ab complex is therefore at equilibrium with its dissociation, and the equilibrium association constant (KA) of the complex can be calculated as follows:

K_A=l/k_d=[Ag-Ab]/[Ag][Ab]

[00125] Binding entities can be separated from impurities before incorporation into the devices. For example, the binding entities can be purified or isolated using purification methods such as electrophoretic, molecular, immunological and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing, and the like. The degree of purification necessary will vary depending on the contaminants present with the binding entities. In some instances no purification will be necessary (e.g., when binding entities are commercially available and provided in purified form).

[00126] When generating a lateral flow device, mobile binding entities can be labeled with various detectable labels such as colored particles or metals. Examples include colloidal gold, natural polymers such as latex (e.g., latex particle, latex microparticle), polymer microspheres or microbeads, quantum dots, magnetic particles, glass beads (e.g., colored glass beads), fluorescent dyes, luminescent dyes, and the like. Preferably, the particles are detectable and can be easily visualized by eye, for example, by being colored.

[00127] Immobilized binding entities can be incorporated into the devices described herein by available procedures.

Labels

[00128] A variety of different labels can be used in the methods, kits, and devices described herein. Examples of labels include, but not limited to, fluorophores, chromophores, radiophores, enzymatic tags, antibodies, chemiluminescence, electroluminescence, metals, liposomes, RFID tags, electrical, and affinity labels. One of skill in the art will recognize that these and other labels can be used with success in this invention. Examples of enzyme labels include enzymes such as urease, alkaline phosphatase or peroxidase to mention a few. Colorimetric indicator substrates can be employed to provide a detection means visible to the human eye or spectrophotometrically. Examples of fluorophores include, but are not limited to, Alexa 350, Alexa 430, AMCA, BODIPY 630/650, BODIPY 650/665, BODIPY-FL, BODIPY-R6G, BODIPY -TMR, BODIPY-TRX, Cascade Blue, Cy2, Cy3, Cy5, 6- FAM, Fluorescein, HEX, 6-JOE, Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, REG, Rhodamine Green, Rhodamine Red, ROX, TAMRA, TET, Tetramethylrhodamine, and Texas Red.

[00129] Binding entities can be covalently attached to such labels. For example, one type of binding entity (e.g., a mobile binding entity) can have a covalently bound label, while another type of binding entity can have no label, so that a satiety factor can form a sandwich between labeled and unlabeled binding entities.

Alternatively, a label can be non-covalently or indirectly bound to a binding entity. For example, the label can be an enzyme substrate that is transformed by an enzyme bound to a binding entity into a colored signal.

[00130] Means of detecting such labels are well known to those of skill in the art. For example, fluorescent markers may be detected using a photodetector to detect emitted light. In still further examples, enzymatic labels are detected by providing the enzyme with a substrate and detecting the reaction product produced by the action of the enzyme on the substrate, and colorimetric labels are detected by simply visualizing the colored label or by use of spectrometer.

[00131] So called "direct labels" are detectable labels that are directly attached to or incorporated into a binding entity that then can bind to a satiety factor. In contrast, so- called "indirect labels" are joined to a complex formed between a satiety factor and a binding entity after complex formation. For example, an indirect label can be part of the development solution used for a test strip.

Kits

[00132] Disclosed herein are kits for use in detecting and monitoring satiety in a sample (such as, a biological fluid). The kits can include separately packaged components, and/or a series of separately packaged satiety detection devices, with instructions for using the satiety detection devices. For example, the kits can include at least one package containing a series of satiety detection devices, where the package is similar in size to a package of gum. The device package in the kits can therefore be small enough to be carried in a pocket or handbag. The kits can also include larger components. However, in general the components of the kits are separately small enough for easy transportation in a pocket or handbag. An example kit including a package 315 containing satiety detection devices 305 is illustrated in FIG. 3.

[00133] The kits can include one or more satiety detection devices as disclosed herein, for example, any of the dipsticks, test strips, nanowire-containing devices, direct-charge transfer conductometric biosensor devices, radio frequency

identification (RFID) devices, and/or lateral flow devices with any of the features described herein. The instructions can explain how to use the devices, and what the results of testing mean. The instructions can also include directions for using the satiety detection devices with a smart device, for example, how to acquire an application (e.g., at a specific website) for converting a photograph of results displayed by a satiety detection device to a measure of satiety, how to store the results on a smart device for later review and analysis, how to graph the results over time, and a combination thereof. [00134] The kits can include a backing for the satiety detection device(s), where the backing is configured to support and hold a satiety detection device. The devices can include a transmitter as described herein. However, the backing can also include electric contacts that can receive a signal from the satiety detection devices and transmit it to a smart device. The backing can also receive power, and/or instructions from the smart device that can be transmitted to the satiety detection device(s). A connection plug can be included in the kit to electrically join the backing to a smart device. For example, the kits can include any one of plug 400 and backing 510 illustrated in FIGs. 4C-4E.

[00135] The kits can also include a carrier means for the devices as well as other components of the kits. Such a carrier can be a box, a bag, a satchel, plastic carton (such as molded plastic or other clear packaging), wrapper (such as, a sealed or sealable plastic, paper, or metallic wrapper), or other container. In some examples, kit components will be enclosed in a single packaging unit, such as a box or other container, which packaging unit may have compartments into which one or more components of the kit can be placed. In other examples, a kit includes one or more containers, for instance vials, tubes, and the like that can retain, for example, one or more biological samples to be tested, positive and/or negative control samples or solutions (such as, a positive control solution containing one or more satiety factors in known and specified concentration), diluents (such as, phosphate buffers, or saline buffers), detector reagents (e.g., for immersion or external application to a kit device), substrate reagents for visualization of detector reagent enzymes (such as, 5- bromo-4-chloro-3-indolyl phosphate, nitroblue tetrazoliurn in dimethyl formamide), and/or wash solutions (such as, Tris buffers, saline buffer, or distilled water).

[00136] Kits can also contain vials, syringes, finger-prick devices, alcohol swabs, gauze squares, cotton balls, bandages, latex gloves, incubation trays with variable numbers of troughs, adhesive plate sealers, data reporting sheets, which may be useful for handling, collecting and/or processing a biological sample. When the satiety detection devices are configured for detection of satiety levels in saliva samples the syringes, finger-prick devices, alcohol swabs, gauze squares, cotton balls, bandages, and latex gloves, may not be needed in the kits. Kits may also optionally contain implements useful for introducing samples into a sample chamber of a satiety detecting device, including, for example, droppers, Dispo-pipettes, capillary tubes, rubber bulbs (e.g., for capillary tubes), and the like. Other components can also be present in the kits such as disposal means for discarding used devices and/or other items used with the device (such as patient samples, etc.). Such disposal means can include, without limitation, containers that are capable of containing leakage from discarded materials, such as plastic, metal or other impermeable bags, boxes or containers.

[00137] The kits can include instructions for the use of an immunoassay, lateral flow devices, a direct-charge transfer conductometric biosensors, test strips, a nanowire biosensors, radio frequency identification (RFID) devices, and

combinations thereof. The instructions may provide direction on how to apply sample to the test device (e.g., by pressing the device to the tongue for a few seconds), the amount of time necessary or advisable to wait for results to develop, and details on how to read and interpret the results of the test.

[00138] Such instructions may also include instructions on how to obtain an application for a smart device to receive, display, interpret, store and/or graph the test results provided by the satiety detection device. For example, directions on taking a photograph of test results displayed on a satiety detection device can also be included in the instructions, as well as directions on how to acquire an application for a smart device to store, interpret, and display the results over time. The instruction can also include information about how to use standards, or incorporate information about standards into the interpretation of results, such as by providing standard tables, graphs, or pictures for comparison of the results of a test. These standards can optionally include the information necessary to quantify one or more satiety factors while using the device, such as a standard curve relating intensity of signal, signal shape, or number of signal lines to an amount of satiety factor present in the sample.

[00139] Preferred kits are small with devices that measure the amount and/or type of satiety factor(s) in a saliva sample, and with an easily interpreted readout. Simple instructions are also preferred where the sample application is at room temperature or at physiological temperatures; the sample incubation in the device is fast and at room temperature; and the readout is simple to understand and provided in real-time. For example, the readout can be a white or green signal indicating that the subject is not yet physiologically satiated, or a yellow signal indicating that the subject is approaching satiation but has not yet reached satiation, or a red signal indicating that the subject is physiologically satiated.

[00140] The following non-limiting Examples illustrate aspects of the invention.

Prophetic Example 1: Illustrating a Test for Satiety Factors

[00141] This Example illustrates a test for detecting one or more satiety factors in a bodily fluid such as saliva.

[00142] A series of antibody preparations, each selectively binding to a different satiety factors are adsorbed or linked to separate wells of a microtiter plate. For example, an anti-cholecystokinin antibody preparation is available from Enzo Life Sciences (see, e.g., enzolifesciences.com/BML-CA1125/cholecystokinin-8-pab/), an anti-ghrelin antibody is available from EMD Millipore Chemicals (see, e.g., millipore.com), an anti-melatonin antibody is available from abeam (see, e.g., abcam.com/melatonin-antibody-ab35137.html), anti-proopiomelanocortin antibody preparations are available from antibodies-online (see, e.g., antibodies- online. com/antibody/antigen/ Proopiomelanocortin); anti-bombesin antibody preparations are available from Acris Antibodies Inc. (see, e.g., /us.acris- antibodies.com); anti-amylin antibody preparations are available from abeam (abcam.com/amylin-antibody-abl5125.html). The antibodies can be linked to the wells of the microtiter plate via a linker.

[00143] A fasting sample of saliva is collected from a fasting subject (e.g., a subject who has not eaten for at least six hours). A satiated sample of saliva is collected from the same subject after the subject has eaten a meal that satisfies the subject's physiological needs. The saliva samples can be collected in vials that contain protease inhibitors and other components to inhibit the breakdown of satiety factor peptides.

[00144] For example, to test for ghrelin in the fasting and/or satiated saliva samples, a microtiter plate is prepared with an anti-ghrelin antibody immobilized onto the wells of the plate is prepared. A solution of secondary anti-ghrelin antibodies (mobile antibodies) is also obtained that is linked to an enzyme such as alkaline phosphatase, beta-galactosidase, or horseradish peroxidase. The enzymes produce a colored product upon reaction with a substrate. For example, an enzyme such as alkaline phosphatase produces a yellow product upon reaction with a p- nitrophenyl phosphate disodium salt substrate, or a green product upon reaction with a 2,2'-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt substrate, or a yellow-orange product upon reaction with an o-phenylenediamine

dihydrochloride substrate, or a blue color upon reaction with a 3,3',5,5'- tetramethylbenzidine substrate. The immobilized and mobile antibodies react with different epitopes on the ghrelin peptide. Substrates for beta-galactosidase include X-gal (also abbreviated BCIG for 5-bromo-4-chloro-3-indolyl-P-D- galactopyranoside), which produces a blue color upon cleavage by beta- galactosidase. Substrates for horseradish peroxidase include 3, 3 ',5,5'- tetramethylbenzidine (TMB) that yields a blue color.

[00145] The fasting sample and the satiated sample of saliva are separately incubated at 37 °C for 1 hour in different wells of the microtiter plate. A series of known amounts of ghrelin can be added to a series of wells to provide a ghrelin standard curve. The wells of the plates are gently rinsed two or three times with a solution such as 0.05% Tween-20 in phosphate buffered saline to remove unbound materials. A solution of the secondary (mobile) antibodies is added to each well, and the microtiter plate is incubated at 37 °C for 1 hour.

[00146] The microtiter wells are drained and gently washed three times with phosphate buffered saline (optionally containing 0.05% Tween-20). A solution of substrate for the enzyme linked to the mobile antibody is added to each of the microtitier wells and the plate is incubated for 10 - 60 minutes. The plates are observed for color in the wells, which is an indicator that a saliva sample contains ghrelin.

[00147] The color signal can be scanned with a spectrometer or fluorimeter to determine a relative amount of ghrelin in each well. The signal from the wells containing known amounts of ghrelin can be plotted to generate a standard curve. The amount of ghrelin in the saliva test samples can be determined by comparison of the signals from the saliva test samples to the standard curve. Prophetic Example 2: Illustrating Use of a Satiety Monitoring Device

[00148] A pilot trial is performed with 10-20 obese adults (BMI at least 35) using one of the devices depicted in FIGs. 1A-1F. After three months of monitoring satiety using such a device, the majority of subjects respond positively, with a total weight loss ranging, for example, from 2-9 kg. As the test subjects become retrained by repeated monitoring of their satiety levels, the frequency of eating can decrease and a feeling of fullness can start earlier in the meal than it did before treatment. There can also be an improvement self-esteem amongst adults tested so that the adults become more outgoing, watch less television (from 6 to 2 hr/day), and have increased physical activity.

[00149] All patents and publications referenced or mentioned herein are indicative of the levels of skill of those skilled in the art to which the invention pertains, and each such referenced patent or publication is hereby specifically incorporated herein by reference to the same extent as if it had been incorporated by reference in its entirety individually or set forth herein in its entirety. Applicants reserve the right to physically incorporate into this specification any and all materials and information from any such cited patents or publications.

[00150] The specific methods and compositions described herein are

representative of preferred embodiments and are exemplary and not intended as limitations on the scope of the invention. Other objects, aspects, and embodiments will occur to those skilled in the art upon consideration of this specification, and are encompassed within the spirit of the invention as defined by the scope of the claims. It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. The invention illustratively described herein suitably may be practiced in the absence of any element or elements, or limitation or limitations, which is not specifically disclosed herein as essential. The methods and processes illustratively described herein suitably may be practiced in differing orders of steps, and the methods and processes are not necessarily restricted to the orders of steps indicated herein or in the claims. As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "satiety factor" or "a peptide" includes a plurality of such satiety factors or peptides (for example, a solution of satiety factors or peptides or a series of satiety factor or peptide preparations), and so forth. Under no circumstances may the patent be interpreted to be limited to the specific examples or embodiments or methods specifically disclosed herein. Under no circumstances may the patent be interpreted to be limited by any statement made by any Examiner or any other official or employee of the Patent and Trademark Office unless such statement is specifically and without qualification or reservation expressly adopted in a responsive writing by Applicants.

[00151] The terms and expressions that have been employed are used as terms of description and not of limitation, and there is no intent in the use of such terms and expressions to exclude any equivalent of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention as claimed. Thus, it will be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the appended claims and statements of the invention.

[00152] The following statements of the invention are intended to describe and summarize various embodiments of the invention according to the foregoing description in the specification.

Summary Statements:

1. A device comprising a solid support, and one or more binding entities

supported by the support, the one of more binding entities being specific for cholecystokinin (CCK), melatonin, proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin-concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP), or

oxyntomodulin (OXM).

2. The device of statement 1, wherein the one or more binding entities are

peptides, proteins, antibodies, receptors, channels, and combinations thereof. The device of statement 1 or 2, wherein the device comprises one or more binding entities specific for ghrelin, leptin, glucagon- like peptide 1 (GLP-1), or a combination thereof.

The device of any of statements 1-3, wherein the one or more binding entities form a complex with cholecystokinin (CCK), melatonin,

proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin- concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP), oxyntomodulin (OXM), or a combination thereof.

The device of statement 4, wherein complex formation emits at least one identifiable signal.

The device of any of statements 1-5, wherein at least a first type of binding entity is immobilized on the solid support.

The device of any of statements 1-6, wherein at least a first type of binding entity is immobilized to a capture region of the solid support.

The device of any of statements 1-7, comprising at least one labeled binding entity that comprises a binding entity with a label covalently linked thereto. The device of statement 8, wherein the label is detectable as a visual, electrical, radio and/or electromagnetic signal.

The device of statement 8 or 9, wherein the label comprises colloidal gold particles, latex microspheres, a glass beads, fluorescent dyes, luminescent dyes, enzymes, enzyme substrates, metals, liposomes, ions, electrical conductors, radio frequency identification tags, or any combination thereof. The device of any of statements 1-10, comprising at least one second type of binding entity.

The device of statement 11, wherein the at least one second type of binding entity is a mobile antibody that is not immobilized on the solid support and is not linked to the solid support.

The device of statement 11 or 12, wherein the at least one second type of binding entity is covalently attached to a label.

The device of any of statements 11-13, wherein the at least one second type of binding entity is covalently attached to a label selected from the group consisting of colloidal gold particles, latex microspheres, a glass beads, fluorescent dyes, luminescent dyes, enzymes, enzyme substrates, metals, liposomes, ions, electrical conductors, radio frequency identification tags, and a combination thereof.

The device of any of statements 1-14, wherein at least one type of binding entity is within a matrix of the solid support.

The device of statement 15, wherein the binding entity is immobilized to the solid support, substantially throughout the length and width of the solid support.

The device of any of statements 1-16, wherein the support is selected from the group consisting of cellulose, ethylcellulose, methylcellulose, nitrocellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, plastic, polystyrene, polyethylene, lipid polydiacetylene (PDA),

polydimethylsiloxane, nylon, rayon, cotton, teflon, mica, sephadex, sepharose, polyacrylonitrile, glass, glass-fiber paper, gold, silicon, silica, paper, and combinations thereof.

The device of any of statements 1-17, wherein the device is a dipstick, a test strip, a direct-charge transfer conductometric biosensor, a radio frequency identification (RFID) device, a nanowire, and/or a lateral flow device.

The device of any of statements 1-18, configured for detection of cholecystokinin (CCK), melatonin, proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin-concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP),

oxyntomodulin (OXM), or a combination thereof in a bodily fluid sample comprising saliva, mucus, blood, sweat, or a combination thereof.

The device of any of statements 1-19, configured for application to a subject's tongue.

The device of any of statements 1-20, configured for transportation by a subject in a pocket, purse, handbag, briefcase, or backpack.

The device of any of statements 1-21, further comprising a wireless or radio transmitter. The device of any of statements 1-22, configured for direct attachment to a smart device.

The device of any of statements 1-23, wherein the support is integral with a backing.

The device of any of statements 1-23, wherein the support is configured to joined to a backing.

The device of any of statements 23-25, wherein the backing is configured for connection to a smart device via a detachable connection plug.

The device of any of statements 1-26, configured for wireless

communication with a smart device (for example, by Bluetooth or by acquisition of a photographic image).

The device of any of statements 1-27, configured for communication with a smart device having a camera.

The device of any of statements 23-28, wherein the smart device is a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, RFID detector, or any combination thereof.

The device, of any of statements 1-29, configured to provide a quantitative or qualitative measurement of a subject's physiological degree of satiety.

The device of any of statements 1-30, further comprising one or more central processing units.

The device of any of statements 1-31, further comprising one or more central processing units and machine-readable hardware storage devices configured to store the identifiable signal.

The device of any of statements 1-32, further comprising a radio frequency identification tag that can be activated by contact with a bodily fluid (e.g., saliva).

The device of any of statements 1-33, further comprising one or more standard detection areas, one or more volume detection areas, or a combination thereof.

A method of monitoring satiety in a mammalian subject, comprising contacting the device of any of statements 1-34 with a bodily fluid from the mammalian subject, and observing whether an identifiable signal is generated by the device.

The method of statement 35, wherein the identifiable signal is displayed when satiety levels of cholecystokinin (CCK), melatonin,

proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin- concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP), oxyntomodulin (OXM), or a combination thereof, are present in the bodily fluid.

The method of statement 35 or 36, wherein the bodily fluid is contacted with a sample application area of the device.

The method of any of statements 35-37, further comprising establishing a non-satiated baseline signal level by observing or noting the signal level from the label after testing a bodily fluid from a fasting subject.

The method of any of statements 35 - 38, further comprising establishing a non-satiated baseline signal level by recording a quantified non-satiated signal from the label after testing a bodily fluid from a fasting subject.

The method of any of statements 35 - 39, further comprising establishing a definitive satiated signal level by observing or noting the signal level from the label after testing a bodily fluid from a subject who is consuming or has consumed a meal.

The method of any of statements 35 - 40, further comprising establishing a definitive satiated signal level by recording a quantified signal level from the label after testing a bodily fluid from a subject who is consuming or has consumed a meal.

The method of statement 39 or 41, wherein the meal satisfies the

physiological (e.g., caloric) needs of the subject.

The method of any of statements 35-42, wherein the subject has an eating disorder.

The method of any of statements 35-43, wherein the subject is overweight or obese.

The method of any of statements 35-44, wherein the subject is anorexic. The method of any of statements 35-45, wherein the subject is seeking an ideal weight.

The method of any of statements 35-46, further comprising monitoring the subject's satiety at one or more meals per day.

The method of any of statements 35 - 47, further comprising monitoring the subject's satiety at one or more meals per day for at least one week, or at least two weeks, or at least three weeks.

The method of any of statements 35 - 48, further comprising monitoring the subject's satiety at one or more meals per day for about 1- 12 months, or about 1-24 months.

The method of any of statements 35 - 49, further comprising indefinitely monitoring the subject's satiety at one or more meals per day.

The method of any of statements 35-50, wherein the bodily fluid is saliva, mucus, gastric fluid, blood, serum, urine, or a combination thereof.

The method of any of statements 35-50, wherein the bodily fluid is saliva. The method of any of statements 35-52, wherein the mammalian subject self- monitors his or her own satiety.

The method of any of statements 35-53, wherein the mammalian subject observes the identifiable signal generated by the device and waits to eat when the signal indicates that the subject is satiated.

The method of any of statements 35-54, further comprising one or more central processing units configured to store, transmit, interpret, graph, and or display the signal.

The method of any of statements 35-55, wherein the satiety detection device or the smart device is configured to display a graph showing over time, the results of the satiety detection device test.

The method of any of statements 35-56, wherein the mammalian subject is trained to eat when actually physiologically hungry.

The method of any of statements 35-57, wherein the mammalian subject takes a photograph of results displayed by the satiety detection device. The method of any of statements 35-58, wherein the mammalian subject takes a photograph of results displayed by the satiety detection device with a smart device that can store, display, interpret, and/or graph the results.

The method of any of statements 35-59, wherein the satiety detection device further comprises one or more standard detection areas, one or more volume detection areas, or a combination thereof.

A kit comprising the device of any of statements 1-34, and instructions for using the device.

The kit of statement 61, wherein each device is separately and/or sterilely packaged.

The kit of statement 61 or 62, comprising a series of devices.

The kit of any of statements 61-63, comprising a series of devices packaged for easy transport in a pocket, wallet, briefcase, backpack, handbag, or purse. The kit of any of statements 61-64, comprising a series of devices like gum sticks in an easily transported container.

The kit of any of statements 61-65, further comprising a backing configured to hold one of the devices.

The kit of any of statements 61-66, further comprising a connection plug for attachment of the device to a smart device.

The kit of any of statements 61-67, further comprising a connection plug for attachment of the device to a smart device, wherein the connection plug is integrated into a backing for the device.

The kit of any of statements 61-68, further comprising a connection plug for attachment of the device to a smart device, wherein the connection plug is configured for detachable connection to a backing for the device.

The kit of any of statements 61-69, further comprising a connection plug for attachment of the device to a smart device wherein the smart device is a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, RFID detector, or any combination thereof.

The kit of any of statements 61-70, further comprising a handheld computer or smart device configured to receive a signal from the device(s) and provide a satiety readout, wherein the handheld computer or smart device is, or is capable of transmitting the signal to, a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, RFID detector, or any combination thereof.

The kit of any of statements 61-71, wherein the instructions describe how to acquire a program that configures a smart device to receive, store, display, interpret, and/or graph test results of the satiety detection device.

The kit of any of statements 61-72, wherein the instructions instruct the mammalian subject to take a photograph of results displayed by the satiety detection device with a smart device that can store, display, interpret, and/or graph the results over time.

The kit of any of statements 61-73, wherein the satiety detection device or the smart device is configured to display a graph showing over time, the results of the satiety detection device test.

The kit of any of statements 61-74, wherein the package has a quick- response (QR) code.

A method comprising:

receiving a satiety device signal;

storing the satiety device signal;

converting the satiety device signal to a graphic form; and displaying the graphic form of the satiety device signal.

The method of statement 76, wherein the satiety device signal is a photographic image.

One or more computer-readable hardware storage devices having embedded therein a set of instructions which, when executed by one or more processors of a computer, causes the computer to execute operations comprising:

receiving a satiety device signal;

storing the satiety device signal;

converting the satiety device signal to graphic form; and

displaying the graphic form of the satiety device signal.

The one or more computer-readable hardware storage devices of statement 78 wherein the satiety device signal is a photographic image.

A system comprising: one or more computer processors and storage configured to receive a satiety device signal;

store the satiety device signal;

convert the satiety device signal to graphic form; and display the graphic form of the satiety device signal.

81. The system of statement 80 wherein the satiety device signal is a

photographic image.

[00153] The teachings of all patents, published applications and references cited herein are incorporated by reference in their entirety.

[00154] While this invention has been particularly shown and described with references to example embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims

CLAIMS What is claimed is:

1. A method comprising:

a) applying a mammalian subject's bodily fluid to a satiety detection device; and

b) observing whether a signal from the device indicates that the subject is satiated,

wherein the device comprises a solid support, and one or more types of binding entities specific for one or more satiety factors.

2. The method of claim 1, wherein the device generates a signal when a

complex forms between at least one of the binding entities and at least one satiety factor.

3. The method of claim 1 or 2, wherein the one or more satiety factors are selected from the group consisting of cholecystokinin (CCK), melatonin, proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin- concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP), and oxyntomodulin (OXM).

4. The method of any of claims 1-3, wherein the one or more binding entities are peptides, aptamers, proteins, antibodies, receptors, or channels.

5. The method of any of claims 1-4, wherein the signal is a visually detectable qualitative or quantitative signal.

6. The method of any of claims 1-5, wherein the signal is an electrical or radio signal.

7. The method of any of claims 1-6, comprising at least one labeled binding entity that comprises a binding entity with a label covalently linked thereto.

8. The method of any of claims 1-7, wherein at least a first type of binding entity is immobilized on the solid support.

9. The method of any of claims 1-8, wherein at least a first type of binding entity is immobilized to a capture region of the solid support.

10. The method of any of claims 7-9, wherein the label is visually detectable.

11. The method of any of claims 7-10, wherein the signal is an electrical or radio signal.

12. The method of any of claims 7-11, wherein the label comprises one or more colloidal gold particles, latex microspheres, colored glass beads, fluorescent dyes, luminescent dyes, enzymes, enzyme substrates, metals, liposomes, ions, electrical conductors, radio frequency identification tags, or any combination thereof.

13. The method of any of claims 1-12, comprising at least one second type of binding entity.

14. The method of claim 13, wherein the at least one second type of binding entity is a mobile antibody that is not immobilized on the solid support and is not linked to the solid support.

15. The method of claim 13 or 14, wherein the at least one second type of

binding entity is covalently attached to a label.

16. The method of any of claims 13-15, wherein the at least one second type of binding entity is covalently attached to a label selected from the group consisting of colloidal gold particles, latex microspheres, colored glass beads, fluorescent dyes, luminescent dyes, enzymes, enzyme substrates, metals, liposomes, ions, electrical conductors, radio frequency identification tags, and any combination thereof.

17. The method of any of claims 1-16, wherein at least one type of binding entity is within a matrix of the solid support.

18. The method of any of claims 1-17, wherein the device is configured for flow of a mobile binding entity along the length of the solid support.

19. The method of any of claims 1-17, wherein an immobilized binding entity is immobilized to the solid support substantially throughout the length and width of the solid support.

20. The method of any of claims 1-18, wherein an immobilized binding entity is immobilized to a segment of the solid support.

21. The method of any of claims 1-20, wherein the support is selected from the group consisting of cellulose, ethylcellulose, methylcellulose, paper, nitrocellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, polystyrene, polyethylene, lipid polydiacetylene (PDA),

polydimethylsiloxane, nylon, rayon, cotton, teflon, mica, sephadex, sepharose, polyacrylonitrile, glass, glass-fiber paper, gold, silicon, silica, and combinations thereof.

22. The method of any of claims 1-21, wherein the device comprises a lateral flow device, a direct-charge transfer conductometric biosensor, a radio frequency identification (RFID) device, a nanowire, a flexible test strip, dip stick, or a combination thereof.

23. The method of any of claims 1-22, further comprising establishing a non- satiated baseline signal level by observing or noting the signal level after testing a bodily fluid from a fasting subject.

24. The method of any of claims 1-23, further comprising establishing a non- satiated baseline signal level by recording a quantified non-satiated signal after testing a bodily fluid from a fasting subject.

25. The method of any of claims 1-24, further comprising establishing a

definitive satiated signal level by observing or noting the signal level after testing a bodily fluid from a subject who has consumed a meal, or is consuming a meal.

26. The method of any of claims 1-25, further comprising establishing a definitive satiated signal level by recording a quantified signal level after testing a bodily fluid from a subject who has consumed a meal, or is consuming a meal.

27. The method of claim 25 or 26, wherein the meal satisfies the caloric needs of the subject.

28. The method of any of claims 1-27, wherein the subject is seeking an ideal body weight.

29. The method of any of claims 1-28, wherein the subject has an eating

disorder.

30. The method of any of claims 1-29, wherein the subject is overweight or obese.

31. The method of any of claims 1-28, wherein the subject is anorexic.

32. The method of any of claims 1-31, further comprising monitoring the

subject's satiety at one or more meals per day.

33. The method of any of claims 1-32, further comprising indefinitely

monitoring the subject's satiety at one or more meals per day.

34. The method of any of claims 1-33, wherein the bodily fluid is saliva, mucus, gastric fluid, or a combination thereof.

35. The method of any of claims 1-34, wherein applying a subject's bodily fluid to a satiety device comprises pressing the satiety device to the subject's tongue.

36. The method of any of claims 1-35, wherein the method monitors and/or trains the subject's eating habits.

37. The method of any of claims 1-36, wherein the method monitors and/or trains the subject's eating habits by detecting and/or quantifying the subject's own satiety factor(s).

38. The method of any of claims 1-37, wherein the subject self-monitors his or her satiety.

39. The method of any of claims 1-38, wherein the device further comprises one or more central processing units and machine-readable hardware storage devices configured to store the identifiable signal.

40. The method of any of claims 1-39, wherein the device is configured for communication of a signal to a smart device wherein the signal is a qualitative or quantitative signal of the subject's satiety.

41. The method of any of claims 1-40, wherein the device is configured for communication of an electrical, or radio signal to a smart device.

42. The method of any of claims 1-41, wherein the smart device is a small

pocket computer, a laptop, a netbook, a desktop computer, a smart phone, RFID detector, or any combination thereof.

43. The method of any of claims 1-42, further comprising recording, storing, or interpreting a signal displayed by the satiety detection device.

44. The method of any of claims 1-43, further comprising photographing the signal displayed by the satiety detection device with a smart device.

45. The method of any of claims 1-44, further comprising detecting a radio

signal with a smart device, where the radio signal is from the satiety detection device in contact with the bodily fluid.

46. The method of any of claims 1-45, further comprising detecting a quick- response (QR) code on a satiety detection device package with a smart device.

47. The method of claim 45 or 46, wherein the radio signal or the code activates the smart device to recognize, record, analyze, graph, and/or display a satiety test signal from a satiety detection device.

48. The method of any of claims 1-47, wherein the satiety detection device

further comprises one or more standard detection areas, one or more volume detection areas, or a combination thereof.

49. A satiety detection device comprising:

a) a solid support; and

b) one or more binding entities supported by the support, the one or more binding entities being specific for one or more satiety factors selected from the group consisting of cholecystokinin (CCK), melatonin, proopiomelanocortin, ghrelin, bombesin, amylin, corticoptropin-releasing factor, galanin, melanin-concentrating hormone, neurotensin, agouti-related protein, leptin, neuropeptide Y, glucagon- like peptide 1 (GLP-1), pancreatic polypeptide (PP), and oxyntomodulin (OXM).

50. The device of claim 49, wherein the one or more binding entities are

peptides, proteins, aptamers, antibodies, receptors, or channels.

51. The device of claim 49 or 50, wherein the one or more binding entities form a complex with one or more satiety factors.

52. The device of any of claims 49-51 , comprising at least one binding entity that comprises a binding entity with a label covalently linked thereto.

53. The device of any of claims 49-52, wherein the at least one binding entity is covalently attached to a label that can emit an identifiable signal, the device further comprising one or more central processing units and machine- readable hardware storage devices configured to store the identifiable signal.

54. The device of claim 52 or 53, wherein the label is selected from the group consisting of colloidal gold particles, latex microspheres, a glass beads, fluorescent dyes, luminescent dyes, enzymes, enzyme substrates, metals, liposomes, ions, electrical conductors, radio frequency identification tags, and any combination thereof.

55. The device of any of claims 49-54, wherein complex formation between one or more binding entities and one or more satiety factors emits an identifiable signal, the device further comprising one or more central processing units and machine -readable hardware storage devices configured to store the identifiable signal.

56. The device of any of claims 49-55, wherein at least a first type of binding entity is immobilized to a capture region of the solid support.

57. The device of any of claims 49-56, comprising at least one second type of binding entity.

58. The device of claim 57, wherein the at least one second type of binding entity is a mobile binding entity that is not immobilized on the solid support and is not linked to the solid support.

59. The device of claim 58, wherein the mobile binding entity is covalently attached to a label.

60. The device of any of claims 49-59, wherein at least one type of binding entity is within a matrix of the solid support.

61. The device of claim 60, wherein at least one type of binding entity is

immobilized onto the solid support, substantially throughout the length and width of the solid support.

62. The device of any of claims 49-61, further comprising one or more standard detection areas, one or more volume detection areas, or a combination thereof.

63. The device of any of claims 49-62, wherein the support is selected from the group consisting of cellulose, ethylcellulose, methylcellulose, nitrocellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, polystyrene, polyethylene, lipid polydiacetylene (PDA), polydimethylsiloxane, nylon, rayon, cotton, teflon, mica, sephadex, sepharose, polyacrylonitrile, glass, glass-fiber paper, gold, silicon, silica, and combinations thereof.

64. The device of any of claims 49-63, wherein the device is selected from the group consisting of a lateral flow device, a direct-charge transfer conductometric biosensor, a radio frequency identification (RFID) device, a nanowire, a flexible test strip, dip stick, or a combination thereof.

65. The device of any of claims 49-64, configured for application to a subject's tongue.

66. The device of any of claims 49-65, configured for direct attachment to a smart device.

67. The device of any of claims 49-66, configured for attachment to a backing.

68. The device of any of claims 53-67, further comprising one or more central processing units and machine-readable hardware storage devices configured to store or transmit the identifiable signal.

69. The device of any of claims 53-68, further comprising one or more central processing units and machine-readable hardware storage devices configured to interpret the identifiable signal.

70. The device of any of claims 67-69, wherein the backing is configured for connection to a smart device.

71. The device of any of claims 67-70, wherein the backing is configured for connection to a smart device via a detachable connection plug.

72. The device of any of claims 49-71, configured for wireless communication with a smart device.

73. The device of any of claims 49-72, configured for transportation by a subject in a pocket, purse, handbag, briefcase, or backpack.

74. The device of any of claims 49-73, which is sterilely packaged.

75. A kit comprising the satiety detection device of any of claims 49-74, and instructions for using the device.

76. The kit of claim 75, comprising a series of satiety detection devices

packaged for easy transport in a pocket, wallet, briefcase, backpack, handbag, or purse.

77. The kit of claim 75 or 76, further comprising a backing configured to hold the device.

78. The kit of any of claims 75-77, further comprising a connection plug for attachment of the device to a smart device.

79. The kit of any of claims 75-78, further comprising a connection plug for attachment of the device to a smart device, wherein the connection plug is integrated into a backing for the device.

80. The kit of any of claims 75-78, further comprising a connection plug for attachment of the device to a smart device, wherein the connection plug is configured for detachable connection to a backing for the device.

81. The kit of any of claims 75-80, wherein the device is configured to

communicate with a smart device wherein the smart device is a small pocket computer, a laptop, a netbook, a desktop computer, a smart phone, RFID detector, or any combination thereof.

82. The kit of any of claims 75-81 , wherein instructions instruct the subject to acquire a program that configures a smart device to receive, store, display, interpret, and/or graph test results of the satiety detection device.

83. The kit of any of claims 75-82, wherein the instructions instruct the subject to take a photograph of results displayed by the satiety detection device with a smart device that can store, display, interpret, and/or graph the results over time.

84. A method comprising:

receiving a satiety device signal;

storing the satiety device signal;

converting the satiety device signal to a graphic form; and displaying the graphic form of the satiety device signal.

85. The method of claim 84, wherein the satiety device signal is a photographic image.

86. One or more computer-readable hardware storage devices having embedded therein a set of instructions which, when executed by one or more processors of a computer, causes the computer to execute operations comprising:

receiving a satiety device signal;

storing the satiety device signal;

converting the satiety device signal to graphic form; and displaying the graphic form of the satiety device signal.

87. The one or more computer-readable hardware storage devices of claim 86, wherein the satiety device signal is a photographic image.

88. A system comprising:

one or more computer processors and storage configured to

receive a satiety device signal;

store the satiety device signal;

convert the satiety device signal to graphic form; and display the graphic form of the satiety device signal.

89. The system of claim 88, wherein the satiety device signal is a photographic image.