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WO2024233825A2 - Systèmes, dispositifs et procédés d'enrichissement d'échantillon - Google Patents

Systèmes, dispositifs et procédés d'enrichissement d'échantillon Download PDF

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Publication number
WO2024233825A2
WO2024233825A2 PCT/US2024/028655 US2024028655W WO2024233825A2 WO 2024233825 A2 WO2024233825 A2 WO 2024233825A2 US 2024028655 W US2024028655 W US 2024028655W WO 2024233825 A2 WO2024233825 A2 WO 2024233825A2
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Prior art keywords
airflow
enrichment
sources
porous material
solution
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WO2024233825A3 (fr
Inventor
Yu-Hwa Lo
Edward Wang
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University of California Berkeley
University of California San Diego UCSD
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University of California Berkeley
University of California San Diego UCSD
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Publication of WO2024233825A2 publication Critical patent/WO2024233825A2/fr
Publication of WO2024233825A3 publication Critical patent/WO2024233825A3/fr
Anticipated expiration legal-status Critical
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4022—Concentrating samples by thermal techniques; Phase changes

Definitions

  • PCR Polymerase chain reaction
  • DNA deoxyribonucleic acid
  • a sample preconcentration technique is described through airjet-induced liquid phase enrichment.
  • a disclosed method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation and applying a flow of gas through one or more airjets to increase concentration of the plurality of particles in the solution.
  • a disclosed method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation, applying the solution to a porous membrane, and applying a flow of gas through one or more aiijets to increase concentration of the plurality of particles in the solution.
  • a disclosed method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation, applying the solution to a membrane, the membrane comprising a first porous material and a second porous or non-porous material (i.e., a material that is at least less porous material than the first porous material), and applying airflow from one or more sources to increase concentration of the plurality of particles in the solution.
  • a method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation, applying the solution to a membrane, the membrane comprising a first porous material and a second porous or non-porous material (i.e., a material that is at least less porous material than the first porous material), and applying a differential evaporation rate through airflow from one or more sources between one or more locations of the membrane to increase the concentration of the plurality of particles or dissolved or suspended components in the solution at locations on the membrane where the evaporation rate of the solution is greater.
  • a disclosed device for sample enrichment comprises one or more sources of airflow, a substrate (wherein the substrate may include a non-porous material, and wherein the substrate includes a base and an exterior wall), a membrane (wherein the membrane comprises a first porous material and a second porous or non-porous material (i.e., a material that is at least less porous material than the first porous material), and wherein the first porous material is thinner than the second less porous or non-porous material), and one or more heating units (wherein the one or more heating units are attached to the substrate, the one or more sources of airflow, or a combination thereof).
  • a substrate wherein the substrate may include a non-porous material, and wherein the substrate includes a base and an exterior wall
  • a membrane wherein the membrane comprises a first porous material and a second porous or non-porous material (i.e., a material that is at least less porous material than the first porous material), and wherein the first por
  • the flow of gas applied through one or more airjets reverses radial flow by establishing a large evaporative flux at the center of a droplet of the solution.
  • the flow of gas applied through one or more aiijets displaces a boundary layer comprised of saturated water vapor which lies directly above a liquid-air interface.
  • displacement of the boundary layer leads to enhanced diffusion across the liquidair interface and shifts an evaporative gradient towards an area under the one or more aiijets.
  • the droplet is a sessile droplet.
  • the method of sample enrichment further comprises controlling an overall evaporation rate based at least on controlling temperature of the flow of gas through the one or more airjets. In some embodiments, the method of sample enrichment further comprises controlling an overall evaporation rate based at least on controlling temperature of the solution.
  • the flow of gas applied through the one or more aiijets includes positioning a nozzle above the droplet and directing a jet of air perpendicular to its surface.
  • the plurality of particles include at least one of nucleic acid molecules, polynucleotides, viruses, dissolved components, suspended components, or other type of chemical molecules, compounds, or nanoscale or microscale structures, or a combination thereof.
  • the gas includes at least one of nitrogen, argon, air, or other gas, or a combination thereof.
  • the method of sample enrichment further comprises adding a surfactant to the solution before applying the flow of gas though the one or more aiijets to increase concentration of the plurality of particles in the solution.
  • the surfactant is methyl cellulose, polydimethylsiloxane, or sodium dodecyl sulfate.
  • the one or more aiijets are set up in parallel. In some embodiments, the one or more aiijets are set up in an array. In some embodiments, the one or more aiijets are aimed at the same location. In some embodiments, the one or more aiijets are aimed at more than one location.
  • the porous material(s) of the membrane includes at least one of paper, cotton, microfiber, bamboo, nitrocellulose, or other porous material, or a combination thereof.
  • the porous membrane is a cellulose-based material.
  • the first porous material is thinner than the second less porous or non-porous material.
  • the one or more sources of airflow over one or more areas of the membrane are passive. In some embodiments, the one or more sources of airflow over one or more areas of the membrane are active.
  • the disclosure provides for a device or system for sample enrichment comprising an airjet-induced liquid phase enrichment technique.
  • the disclosed device comprises one or more aiijets, a membrane, and a heating unit.
  • the disclosed device comprises one or more sources of airflow, a membrane, and a heating unit.
  • the heating unit may be, but is not limited to, a metal coil and heating pad.
  • the airjets may additionally comprise a heating unit.
  • the heating unit may, in some embodiments, be a metal coil contained within each of the one or more aiijets.
  • the membrane is porous.
  • the membrane comprises a first porous material and a second porous or non-porous material (i.e., a material that is at least less porous material than the first porous material).
  • the membrane includes at least one of paper, cotton, microfiber, bamboo, nitrocellulose, or other material, or a combination thereof.
  • the porous material(s) includes one or more of paper, cotton, microfiber, bamboo, nitrocellulose, or other porous material, or a combination thereof.
  • the one or more aiijets are set up in parallel. In some embodiments, the one or more aiijets are set up in an array. In some embodiments, the one or more aiijets are aimed at the same location. In some embodiments, the one or more aiijets are aimed at more than one location.
  • the one or more sources of airflow are set up in parallel. In some embodiments, the one or more sources of airflow are set up in an array. In some embodiments, the one or more sources of airflow are aimed at the same location. In some embodiments, the one or more sources of airflow are aimed at more than one location.
  • the one or more sources of airflow are passive. In some embodiments, the one or more sources of airflow are active.
  • Figure 1 shows a diagram of an example embodiment of a sample enrichment method in accordance with the present technology.
  • Figure 2 shows a diagram of an example passive airflow sample enrichment system, in accordance with the present technology.
  • Figure 3 shows a diagram depicting a cross-section of a passive airflow sample enrichment system, in accordance with the present technology.
  • Figure 4 shows a schematic of aiijet enrichment to reverse coffee-ring flows and the comparison of the resulting deposition patterns with that of ambient evaporation.
  • Figure 5 shows: (a) a diagram and images of fluid behavior under an example embodiment of an aiijet, in accordance with the present technology, in the absence (- M.C.) and presence (+ M.C.) of the methyl cellulose surfactant in a droplet as the process progresses (from top to bottom), where the scale bar is 4mm; and (b) a diagram and images from a 96-well plate after enrichment with (+ M.C.) and without (- M.C.) methyl cellulose.
  • Figure 6 shows an image showing an example implementation of enrichment of rhodamine in ethanol .
  • Figure 7 shows fluorescent images of example results from an enrichment implementation in accordance with the present technology, before and after 5 minutes of enrichment with equal exposure time for FITC-tagged DNA oligonucleotides, green fluorescent protein (GFP), 20nm streptavidin-functionalized quantum dots, and 1 pm fluorescent beads.
  • GFP green fluorescent protein
  • Figure 8 shows images depicting a comparison of duplicate ELISA wells for direct and enriched samples after 3 minutes of Tetramethylbenzidine (TMB) development.
  • Figure 9A shows a diagram illustrating an exemplary heated aiijet (left) and associated thermal images (right) taken at specified voltages applied to the heating element.
  • Figure 9B shows data plots depicting temperature profiles of the liquid surface for different voltages and airflow speeds in example implementations of the heated airjet.
  • Figure 10 shows an image of an example embodiment of the heated airjet used for enhanced sample enrichment, in accordance with the present technology.
  • Figure 11 shows a data plot depicting average temperature vs. applied voltage for the pipette’s exit nozzle for an example implementation of the sample enrichment technique using the example heated aiijet of Figure 10.
  • Figure 12A shows a diagram illustrating an example embodiment of a double-stage enrichment process, in accordance with the present technology.
  • Figure 12B shows exemplary data from example implementations of the double-stage enrichment process of Figure 12A.
  • Figure 13 shows data plots depicting a comparison of cumulative ACq (orange) and fold-enrichment (green) for Z-DNA, HeLa-S3 RNA, and heat-inactivated SARS-CoV-2 in 0. ImM EDTA for solutions with PEG (+ PEG) (left plot) and without PEG (- PEG) (right plot).
  • Figure 14 shows a data plot depicting the Cq vs. EDTA concentration for a solution of -DNA in an example implementation of the disclosed technology.
  • Headings are provided for convenience only and are not to be construed to limit the invention in any manner. Embodiments illustrated under any heading may be combined with embodiments illustrated under any other heading.
  • nucleic acid e.g., DNA and RNA
  • an amplification process e.g., qPCR, RT-PCR, LAMP, etc.
  • the amplification process itself is highly sensitive and capable of detecting single copies of the target molecules.
  • the test result could become a false negative result, where the sensitivity of the test may have been compromised.
  • a typical elution process to elute nucleic acids from magnetic beads uses a sample volume of about 150 pL within which the target nucleic acids to be extracted are.
  • the typical elution process only uses 2 pL of the elution buffer for adding to a 20 pL PCR mix.
  • a nasal swap sample for a Covid test may collect around 100 viral particles (i.e., with 50 copies of genetic RNA). As such, one would have a very high chance (e.g., 50% chance) of producing a false negative result in conventional practice, even though PCR or LAMP process itself can be highly sensitive.
  • a sample preconcentration technique is described through airjet-induced liquid phase enrichment.
  • a sample preconcentration technique includes liquid phase enrichment through an evaporative gradient induced by passive or active airflow.
  • the disclosed technology can offer an effective solution for present sample collection challenges with target loss and sample bottleneck.
  • example embodiments of the disclosed sample enrichment devices, systems, and methods can collect >60% target molecules from the original sample, representing 10x to 100* performance enhancement compared to the current state of the art, which can be translated to nearly 0% false negative by the disclosed sample enrichment devices, systems, and methods.
  • the disclosed sample enrichment devices, systems, and methods can greatly improve the sensitivity and reproducibility.
  • the method in accordance with the disclosed technology when the method in accordance with the disclosed technology is applied to protein or antibody tests (e.g., ELISA) where amplification is not possible, the method can increase the sensitivity of the existing assay by 10x to 100* due to the enhanced target collection efficiency.
  • protein or antibody tests e.g., ELISA
  • the disclosed systems, devices, and methods provide an effective sample enrichment technique that can reverse the “coffee ring effect” (CRE) to retain analytes in the liquid during an accelerated evaporation process, confining the analytes in a well-defined area on the liquid surface for easy collection and transfer, and achieving a certain level of selectivity to minimize co-enrichment of salt and other unwanted species.
  • CRE coffee ring effect
  • CRE refers to the analytes and all other non-volatile species, including salts, precipitating on the dry surface in a spatially-distributed pattern during evaporation. CRE occurs because an evaporating droplet forms a differential evaporative gradient having the highest evaporation rate at the droplet’s perimeter. This evaporation rate gradient induces a radially outward flow to drive fluid within the droplet towards the periphery to replenish the lost fluid at the liquid-solid interface. As a result, any solutes or suspended particles are carried to the contact line and deposited.
  • the disclosed technology is configured to solve one bottleneck problem for all molecular diagnosis methods: loss of target molecules during sample preparation. It can significantly increase analyte collection efficiency several hundred times more than current practices thus improving the accuracy and repeatability of in-vitro diagnostic/point-of-care assays.
  • airjet-induced evaporation is used to reverse the coffee-ring flow.
  • the airjet drives analytes from a relatively large droplet periphery towards a smaller central region under an airjet apparatus, in accordance with the disclosed sample enrichment devices, systems, and methods.
  • Coffee-ring flow reversal can be achieved by aiming a nozzle of the aiijet to be perpendicular to the liquid surface and initiating the airjet to increase local evaporation.
  • the localized increase in evaporative flux establishes a differential evaporative gradient and induces fluid flows towards the area to replenish the lost liquid.
  • the flow carries dissolved molecules or suspended particles, which become highly concentrated in a small, localized area underneath the nozzle.
  • the disclosed sample enrichment devices, systems, and methods have a cost-effective design that can include an air source, an air heater, and an aiijet nozzle in some example embodiments.
  • surfactant e.g., methyl cellulose
  • the effectiveness of the approach was demonstrated by concentrating a range of particles and biological analytes — specifically nucleic acids, proteins, and viral and other particles.
  • Spiked samples containing X- DNA, HeLa-S3 RNA, and heat-inactivated SARS-CoV-2 were used as model analytes and reduction of the cycle threshold value (Cq) in real-time PCR (qPCR) analysis was used to quantify analyte enrichment and collection efficiency.
  • Cq cycle threshold value
  • Sample preparation is essential for nucleic acid amplification assays, affecting their sensitivity and reliability.
  • this process often results in a significant loss or dilution of analyte, which becomes a bottleneck that limits downstream assay performance — particularly for assays that accept a limited input sample volume.
  • the disclosed technology provides an evaporation-based, sample enrichment method that includes using an aiijet (in some example embodiments) to concentrate various substances within a small, defined volume by reversing the coffee-ring effect.
  • the concentrated sample can then be collected to increase the initial sample quantity for subsequent analysis.
  • the effectiveness of the reported airjet-based sample enrichment was quantified using qPCR tests for the detection of X-DNA, HeLa-S3 RNA, and heat-inactivated SARS-CoV-2 samples.
  • Comparisons between airjet and conventional evaporative methods demonstrated significant advantages of the disclosed airjet enrichment techniques, including the ability to concentrate a high percentage of analyte within a 1 pL volume.
  • the enhanced sample enrichment method in accordance with the present technology can be integrated and adapted for several fluid volumes commonly found in nucleic acid sample preparation procedures.
  • aiijet enrichment can reduce the overall Cq by an average of 9.27 cycles for each analyte, representing a 600-fold enrichment from the initial concentration.
  • PEG can be added to reduce the co-enrichment of salt.
  • a sample processing method was developed to concentrate the analytes within a small volume (e.g., 1-2 pL) prior to testing, such as nucleic acid amplification reactions.
  • the exemplary liquid-phase sample enrichment method has some selectivity for nucleic acids or protein to suppress the simultaneous concentration of extraneous solutes and improve signal-to-noise. This method is applicable to various biomolecules, as well as amplification and detection methods.
  • the CRE pattern occurs because an evaporating droplet forms a differential evaporative gradient having the highest evaporation rate at the droplet’s perimeter. This evaporation rate gradient induces a radially outward flow to drive fluid within the droplet towards the periphery to replenish the lost fluid at the liquid-solid interface. As a result, any solutes or suspended particles are carried to the contact line and deposited. CRE reversal can be achieved through electroosmosis, electrowetting, surface wave acoustics, infrared laser heating, or microfabricated surface patterning. However, these processes are generally complicated and depend on the properties of the particles such as particle size, charge, hydrophobicity, etc.
  • evaporation methods enrich the analytes and other solutes, such as salts, that can interfere with downstream analysis.
  • the example embodiments and implementations described herein for the present technology demonstrates an effective sample enrichment method that can reverse the CRE to retain analytes in the liquid during an accelerated evaporation process; confining the analytes in a well-defined area on the liquid surface for easy collection and transfer by a pipette, and achieve a certain level of selectivity to minimize co-enrichment of salt and other unwanted species.
  • a sample enrichment technique uses aiijet-induced evaporation to reverse the coffee-ring flow.
  • particles e.g., chemical species, dissolved or suspended components like molecules or compounds
  • a flow of gas such as from one or more fans
  • particles in solution are set under ambient evaporation and one or more sources of airflow, such as from one or more fans or one or more vacuums, generate a differential evaporation gradient.
  • particles in solution are set under ambient evaporation and one or more sources of passive airflow to generate a differential evaporation gradient.
  • the flow of gas can be generated from airjets, fans, vacuums, and like devices capable of moving gases, or a combination thereof.
  • the airjet drives analytes from a relatively large droplet periphery towards a smaller central region under the airjet.
  • Coffee-ring flow reversal is achieved by aiming the nozzle perpendicular to the liquid surface and initiating the airjet to increase local evaporation.
  • the localized increase in evaporative flux establishes a differential evaporative gradient and induces fluid flows towards the area to replenish the lost liquid.
  • the flow carries dissolved molecules or suspended particles, which become highly concentrated in a small, localized area underneath the nozzle.
  • the disclosed sample enrichment devices, systems, and methods have a cost-effective design that can include an air source, an air heater, and an airjet nozzle in some example embodiments.
  • an air source e.g., an air heater, and an airjet nozzle in some example embodiments.
  • surfactant e.g., methyl cellulose
  • the aiijet enrichment method was employed in both microfluidic and mesofluidic systems to handle sample volumes from ⁇ 100 pL to >lmL to address the sample volumes typically used in laboratory PCR testing.
  • the approach addresses a bottleneck in sample preparation by significantly increasing the analyte collection efficiency several hundred times more than current practices. This increase in starting material can improve the accuracy and repeatability of IVD assays.
  • FIG. 1 shows a diagram depicting an example embodiment of a method for sample enrichment in accordance with the present technology, labeled method 100.
  • the method 100 includes a process 110 to distribute a plurality of particles in a solution on a substrate under ambient evaporation.
  • the particles in the solution can include, but are not limited to, dissolved or suspended components, such as molecules or compounds or nanoscale or microscale structures.
  • the solvent for the solution can be, but is not limited to, water, ethanol, or a combination thereof.
  • the method 100 includes a process 120 to apply a gas flow from one or more sources of airflow to the solution.
  • the process 120 includes applying the gas flow from one or more aiijets to the solution, e.g., directly at the solution or indirectly at the solution. In some example embodiments of the method 100, the process 120 includes applying the gas flow through one or more fans to the solution, e.g., directly or indirectly at the solution. In some example embodiments of the method 100, the process 120 includes a subprocess to selectively position the apparatus to apply the gas flow (e.g., one or more aiijets, one or more fans, one or more vacuums, a combination thereof or other air flow apparatus) to create an airflow distribution with predetermined parameters, including flow rate, temperature, gas constituents, etc.
  • the gas flow e.g., one or more aiijets, one or more fans, one or more vacuums, a combination thereof or other air flow apparatus
  • the method 100 includes a process 130 to controllably evaporate the solution, i.e., area-selective evaporation, and thereby concentrate the particles without loss or harm or other detriment to the particles.
  • Implementations of the process 130 can locate the concentrated particles in a selective portion or portions of the substrate.
  • the concentrated particles may be moved to one or more locations on the substrate.
  • the present technology can be utilized to differentially split and separate distinct particles dissolved in the solution.
  • the method 100 includes a process 140 to retrieve concentration particles from the substrate.
  • the concentrated particles are collected from a membrane.
  • a method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation and applying a flow of gas through one or more airjets to increase concentration of the plurality of particles in the solution.
  • a method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation, applying the solution to a porous membrane, and applying a flow of gas through one or more airjets to increase concentration of the plurality of particles in the solution.
  • a method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation, applying the solution to a membrane, the membrane comprising a first material that is porous and a second material that is less porous than the first porous material or non-porous, and applying airflow from one or more sources to increase concentration of the plurality of particles in the solution.
  • a method for sample enrichment comprises distributing a plurality of particles in a solution under ambient evaporation, applying the solution to a membrane, the membrane comprising a first material that is porous and a second material that is less porous than the first porous material or non-porous, and applying a differential evaporation rate through airflow from one or more sources between one or more locations of the membrane to increase the concentration of the plurality of particles or dissolved or suspended components in the solution at locations on the membrane where the evaporation rate of the solution is greater.
  • the differential evaporation rate through airflow from one or more sources between one or more locations of the membrane provides regions with evaporation rates greater than those at other locations on the membrane.
  • the airflow from one or more sources can generate a greater evaporation rate at the porous section of the material (e.g., first material) than the evaporation rate at the less porous or non-porous section of the material (e.g., second material), where the evaporation rate may be lower by up to several orders of magnitude.
  • the porous section of the material e.g., first material
  • the evaporation rate at the less porous or non-porous section of the material e.g., second material
  • the flow of gas applied through one or more airjets reverses radial flow by establishing a large evaporative flux at the center of a droplet of the solution.
  • the flow of gas applied through one or more aiijets displaces a boundary layer comprised of saturated water vapor which lies directly above a liquid-air interface.
  • displacement of the boundary layer leads to enhanced diffusion across the liquidair interface and shifts an evaporative gradient towards an area under the one or more aiijets.
  • the droplet is a sessile droplet.
  • each nozzle of the one or more aiijets is perpendicular to the surface of the solution. In some embodiments, each nozzle of the one or more aiijets is set up at an angle to the surface of the solution. In some embodiments, each nozzle of the one or more airjets is set up at an angle to the surface of the solution ranging from about 1 degree, about 2 degrees, about 3 degrees, about 4 degrees, about 5 degrees, about 6 degrees, about 8 degrees, about 10 degrees, about 12 degrees, about 15 degrees, about 20 degrees, about 25 degrees, about 30 degrees, about 35 degrees, about 40 degrees, and about 45 degrees. For example, in some embodiments, each nozzle of the one or more airjets is set up at an angle to the surface of the solution between about 1 degree to about 5 degrees.
  • each of the one or more sources of airflow is perpendicular to the surface of the solution. In some embodiments, each of the one or more sources of airflow is set up at an angle to the surface of the solution. In some embodiments, each of the one or more sources of airflow is set up at an angle to the surface of the solution ranging from about 1 degree, about 2 degrees, about 3 degrees, about 4 degrees, about 5 degrees, about 6 degrees, about 8 degrees, about 10 degrees, about 12 degrees, about 15 degrees, about 20 degrees, about 25 degrees, about 30 degrees, about 35 degrees, about 40 degrees, and about 45 degrees. For example, in some embodiments, each of the one or more sources of airflow is set up at an angle to the surface of the solution between about 1 degree to about 5 degrees.
  • the method of sample enrichment further comprises controlling an overall evaporation rate based at least on controlling temperature of the flow of gas through the one or more airjets. In some embodiments, the method of sample enrichment further comprises controlling an overall evaporation rate based at least on controlling temperature of the solution.
  • the flow of gas applied through the one or more aiijets includes positioning a nozzle above the droplet and directing a jet of air perpendicular to its surface.
  • the solution is contained within a substrate.
  • the substrate is flat.
  • the substrate is convex.
  • the substrate is concave.
  • the substrate comprises an exterior wall and a base.
  • the substrate comprises an exterior wall, one or more interior walls, and a base.
  • the substrate comprises a non-porous material or porous material that is substantially less porous than the membrane.
  • the non-porous material of the substrate includes at least one of plastic, metal, glass, or ceramic.
  • the solution includes, but is not limited to, ethanol, water, or a combination thereof.
  • the particles include, but are not limited to, at least one of nucleic acid molecules, polynucleotides, viruses, dissolved components, suspended components, or a combination thereof.
  • the dissolved components and the suspended components may be compounds such as but not limited to EDTA, dyes, fluorescent compounds, or PEG.
  • the gas includes at least one of nitrogen, argon, air, or other gas, or a combination thereof.
  • Gases with a lower moisture content, such as nitrogen and argon, can provide more consistent enrichment results than those with a higher moisture content, such as compressed ambient air.
  • the method of sample enrichment further comprises adding a surfactant to the solution before applying the flow of gas though the one or more aiijets to increase concentration of the plurality of particles in the solution.
  • the surfactant is methyl cellulose, polydimethylsiloxane, or sodium dodecyl sulfate.
  • the one or more aiijets are set up in parallel. In some embodiments, the one or more airjets are set up in an array. In some embodiments, the one or more aiijets are aimed at the same location. In some embodiments, the one or more aiijets are aimed at more than one location.
  • the porous membrane includes at least one of paper, cotton, microfiber, bamboo, nitrocellulose, or other porous material, or a combination thereof.
  • the porous membrane is a cellulose-based material.
  • the porous material is thinner than the non-porous or less porous material.
  • the one or more sources of airflow over one or more areas of the membrane are passive. In some embodiments, the one or more sources of airflow over one or more areas of the membrane are active.
  • the disclosure provides for a device or system for sample enrichment comprising an airjet-induced liquid phase enrichment technique.
  • a device comprises one or more aiijets, a membrane, and a heating unit.
  • the disclosed device comprises one or more sources of airflow, a membrane, and a heating unit.
  • the heating unit may be, but is not limited to, a metal coil and heating pad.
  • the aiijets may additionally comprise a heating unit.
  • the heating unit may, in some embodiments, be a metal coil contained within each of the one or more aiijets.
  • the membrane is porous.
  • the membrane comprises a first material that is a porous material and a second material that is a non- porous material or substantially less porous material.
  • the membrane includes, but is not limited to, paper, cotton, microfiber, bamboo, nitrocellulose, or a combination thereof.
  • the porous material includes at least one of paper, cotton, microfiber, bamboo, nitrocellulose, or other porous material, or a combination thereof.
  • the porous membrane can have pores that range from less than about 1 mm, less than about 0.1mm, less than about 0.01 mm, less than about 1 pm, less than about 0.5 pm, less than about 0.1 pm, and less than about 0.05 pm.
  • the porous membrane may have pores that are less than about 0.5 pm to less than about 0.1 pm.
  • the pores in the porous membrane are evenly distributed. In some embodiments, the pores in the porous membrane are randomly distributed.
  • the porous material has pores that range from less than about 1 mm, less than about 0.1mm, less than about 0.01 mm, less than about 1 pm, less than about 0.5 pm, less than about 0.1 pm, and less than about 0.05 pm.
  • the porous material may have pores that are less than about 0.5 pm to less than about 0.1 pm.
  • the pores in the porous material are evenly distributed. In some embodiments, the pores in the porous material are randomly distributed.
  • the porous material has pores that range from about 10 cm, about 5 cm, about 1 cm, about 50 mm, about 10 mm, about 5 mm, about 1 mm, about 0.5 mm, and about 0.1 mm.
  • the non-porous material may range in thickness from about 5 cm to about 0.5 mm.
  • the membrane can conduct heat.
  • the porous material can conduct heat.
  • the non-porous material or substantially less porous material can conduct heat.
  • the one or more aiijets are set up in parallel. In some embodiments, the one or more aiijets are set up in an array. In some embodiments, the one or more aiijets are aimed at the same location. In some embodiments, the one or more aiijets are aimed at more than one location.
  • the one or more sources of airflow are set up in parallel. In some embodiments, the one or more sources of airflow are set up in an array. In some embodiments, the one or more sources of airflow are aimed at the same location. In some embodiments, the one or more sources of airflow are aimed at more than one location. [0097] In some embodiments, the one or more sources of airflow are passive. In some embodiments, the one or more sources of airflow are active. An example of an active source of airflow may be, but is not limited to, fans.
  • a disclosed device for sample enrichment comprises one or more sources of airflow; a substrate, wherein the substrate is a non-porous material (or material of substantially low porosity), and wherein the substrate includes a base and an exterior wall; a membrane, wherein the membrane comprises a porous material and a non-porous material (or second porous material of substantially less pores than the porous material), and wherein the porous material is thinner than the non-porous or less porous material; and one or more heating units, wherein the one or more heating units are attached to the substrate, the one or more sources of airflow, or a combination thereof.
  • Sample enrichment can occur in a setup where an evaporative gradient is established, regardless of whether there is active or passive airflow present.
  • One demonstration using passive airflow is shown in Figure 2.
  • FIG. 2 shows a diagram of an example passive airflow sample enrichment system, in accordance with the present technology, containing both a first porous material and a second less-porous or non-porous material in a membrane, with the first porous material in the center of the membrane.
  • the diagram shows an airflow 201 will preferentially travel through a thinner and more porous membrane 202 as compared to the bulk material 203, which is a less porous or non-porous material.
  • the porous membrane 202 is one that can permit a flow of gas or liquid through while maintaining some absorbency to contain a portion of the solution.
  • Some examples of porous membranes include, but are not limited to, nitrocellulose, paper, cotton, microfiber, or a combination thereof.
  • the pores may have pores that range from less than about 0.1 mm to less than about 0.05 pm.
  • the pores in the membrane may be evenly distributed or randomly distributed.
  • the bulk material 203 is one that does not permit a flow of gas and does not absorb the solution.
  • Some examples of bulk materials include, but are not limited to, metal, glass, plastic, and ceramic.
  • the bulk material 203 can be a non-porous material, but in some embodiments, the bulk material 203 can include a porous material that is substantially less porous than the porous material of the membrane 202. In some embodiments, for example, the non-porous or less porous material of the bulk material 203 may range in thickness from about 5 cm to about 0.5 mm.
  • any analyte and solution containing particles which is collected in bulk material 203 will be transported towards the area of highest airflow and differential evaporation will result.
  • This evaporation gradient can be used as a pre-enrichment step for sample collection, whereby the porous membrane 202 can be removed and inserted into a specified instrument for downstream analysis.
  • Figure 3 shows a diagram depicting a cross-section of a passive airflow sample enrichment system, in accordance with the present technology, containing both a porous material and a non-porous or substantially less porous material in a membrane.
  • the diagram of Figure 3 shows the cross-section of the membrane with the porous membrane 301 and the bulk material 302 (e.g., non-porous or substantially less porous). While the presence of the porous membrane causes preferential airflow in ambient conditions, it also increases the evaporative gradient in active forms of airflow generation as well. This includes movement, breathing, and powered methods such as fans or vacuums to create airflow across the whole device.
  • Figure 4 shows a schematic of airjet enrichment to reverse coffee-ring flows and the comparison of the resulting deposition patterns with that of ambient evaporation.
  • FIG. 4 illustrates the particle distribution under ambient evaporation and airjet enrichment in a sessile droplet.
  • the development of the CRE has been attributed to the non-uniform evaporative profile across the droplet’s surface.
  • the evaporative flux is greatest at the contact line due to the relatively larger proportion of the liquid-air interface.
  • an evaporative gradient is established at the droplet periphery, and a radially outward flow is formed from the interior to replenish the lost fluid. This flow carries any solutes or suspended particles towards the contact line, forming a familiar ring-like pattern.
  • Aiijet enrichment reverses this radial flow by establishing a large evaporative flux at the center of the droplet by positioning a nozzle above the droplet and directing a jet of air perpendicular to its surface.
  • the airjet displaces the boundary layer comprised of saturated water vapor which lies directly above the liquid-air interface. Displacement of the boundary layer leads to enhanced diffusion across the interface and shifts the evaporative gradient towards the area under the airjet.
  • the speed of enrichment is heavily dependent on the evaporation rate and the temperature of the aiijet can be used to control the overall evaporation rate.
  • Figure 5 shows: (a) a diagram and images of fluid behavior under an example embodiment of an aiijet, in accordance with the present technology, in the absence (- M.C.) and presence (+ M.C.) of the methyl cellulose surfactant in a droplet as the process progresses (from top to bottom), where the scale bar is 4mm; and (b) a diagram and images from a 96-well plate after enrichment with (+ M.C.) and without (- M.C.) methyl cellulose.
  • Figure 5 panel a, demonstrates how the presence of methyl cellulose mitigates the airjet-induced secondary flows to achieve a condensed spot through CRE-reversal.
  • a 20 pL sessile droplet with a uniform yellow dye distribution a central region of blue dye was added to visualize liquid movement.
  • turbulent, vortical flow patterns quickly develop within the droplet upon initiating the airjet. This leads to increased mixing between the blue and yellow dye, eventually forming a uniformly green solution.
  • the turbulent patterns are suppressed and evaporative-driven, radial flow dominates as indicated by the increasingly concentrated blue region of the dye.
  • Figure 6 shows an image showing an example implementation of enrichment of rhodamine in ethanol after 2 minutes.
  • the example implementation included 20 pL of rhodamine solution deposited on a hydrophilic glass surface, and 1 pL of a 1% PDMS solution in hexane was added to the surface of the solution.
  • Figure 7 shows images before and after 5 minutes of enrichment with equal exposure time for FITC-tagged DNA oligonucleotides, green fluorescent protein (GFP), 20nm streptavidin-functionalized quantum dots, and 1 pm fluorescent beads.
  • GFP green fluorescent protein
  • Figure 7 shows that airjet enrichment can effectively improve detection sensitivity and concentrate various fluorescent biomacromolecules and particles, regardless of size.
  • Solutions containing FITC-tagged DNA oligonucleotides, green fluorescent protein (GFP), 20nm streptavidin-functionalized quantum dots, and 1pm fluorescent beads were deposited on a hydrophilic glass slide. Methyl cellulose was added to the droplet to prevent fluid turbulence caused by airflow.
  • a glass pipette with a 1.5 mm I.D. exit nozzle was then used to create an aiijet.
  • the gas was provided by a nitrogen tank and the strength of the airjet was controlled by a digital mass flow meter.
  • Figure 8 shows images depicting a comparison of duplicate ELISA wells for direct and enriched samples after 3 minutes of Tetramethylbenzidine (TMB) development.
  • ELISA was performed using rabbit IgG as the antigen.
  • the direct wells contained 1 pL of a 1.3 nM solution deposited into 99 pL of PBS 1 x buffer during the antigen incubation step.
  • For the enriched solution 100 pL of 1.3 nM solution was enriched, and 1 pL of the enriched spot was withdrawn and deposited in 99 pL of PBS l x buffer.
  • Figure 9A shows a diagram illustrating an exemplary heated aiijet (left) and associated thermal images (right) taken at specified voltages applied to the heating element; and Figure 9B shows data plots depicting temperature profiles of the liquid surface for different voltages and airflow speeds in example implementations of the heated airjet.
  • the airjet apparatus can include a heating element, e.g., which may comprise a nichrome coil inserted and sealed in a structure (e.g., glass pipette) of the aiijet and connected to a variable voltage source (see Figure 10).
  • the airjet apparatus can be interfaced with an infrared camera to measure the temperature profiles near the airjet’s nozzle (e.g., pipette’s exit nozzle).
  • Figure 9A shows a data plot depicting different voltages with a constant airflow rate of 1.0 standard liter per minute (sl/m) that were used in exemplary implementations of the example embodiment of the aiijet employing the heating element.
  • a linear relationship between the voltage and mean surface temperature was established (see Figure 11), allowing for control over the airjet temperature.
  • Figure 10 shows an image of an example embodiment of the heated airjet used for enhanced sample enrichment, in accordance with the present technology.
  • the heated airjet includes a nozzle that comprises two halves of a borosilicate glass pipette with the heating element interested in the middle.
  • the heating element includes a 40 mm coil nichrome that is braided at the ends with wire.
  • the glass halves are then sealed with ceramic adhesive.
  • Figure 11 shows a data plot depicting average temperature vs. applied voltage for the pipette’s exit nozzle for an example implementation of the sample enrichment technique using the example heated aiijet of Figure 10.
  • FIG. 9B shows the surface temperature profiles of a liquid solution in a 96-well plate.
  • nichrome heater is turned off (0V)
  • greater airflow rates give rise to lower temperature minimums due to evaporative cooling and quicker boundary layer displacement.
  • this trend is reversed upon applying voltages greater than 3.5V to the heating element, whereby faster airflow rates caused higher peak temperatures through increased levels of heat transfer.
  • voltages under 5.5V did not increase the temperature above 35°C as shown in the temperature readings in Figure 9A, and therefore represented an upper limit to minimize degradation of bioanalytes.
  • Figure 12A shows a diagram illustrating an example embodiment of a double-stage enrichment process, with images from certain steps (i.e., steps 3 and 8).
  • Figure 12B shows data plots in panels b, c, d, and e, depicting: (panel b) collection efficiency vs.
  • the model comprises two stages of fluid processing, each corresponding to a range of fluid volumes that can be enriched.
  • the first stage is the large volume enrichment stage, which can enrich mesofluidic volumes (mLs), followed by the small volume enrichment stage for enriching microfluidic volumes (pLs).
  • Each step is optimized to balance enrichment speed and effectiveness to maximize the overall concentration of analyte prior to analysis.
  • the large volume enrichment stage can typically process 1-3 mL of fluid by maximizing the evaporation rate.
  • This stage has a key component — the insertion of an inner tube (Figure 12A, step 3) where enrichment occurs.
  • the enrichment can be visualized when the tube insert traps and localizes the enriched analytes, as indicated by the blue dye layer from the initially dilute dye solution ( Figure 12A, step 3).
  • the tube insert acts similarly to the stabilizing properties of methyl cellulose, concentrating the enriched fluid while confining the airjet-induced shear forces. Fluid turbulence is less likely to occur due to the smaller tube dimensions. Introducing a physical barrier raises the turbulence threshold, allowing stronger airflow rates enhance the evaporation rate significantly.
  • the inner tube acts as a collection vessel and transfer pipette for the next stage ( Figure 12A, steps 4-5).
  • the small-volume enrichment takes place in a 96-well plate and is designed to maximize the enrichment factor for microfluidic volumes. This stage utilizes methyl cellulose as the stabilizing additive and leads to a highly concentrated spot after enrichment (Figure 12 A, step 8).
  • Figure 12B, panel b The effectiveness of aiijet enrichment over conventional evaporative volume reduction is shown in Figure 12B, panel b by tracking the collection efficiency for a -DNA solution over time. The collection efficiency is determined though qPCR by comparing the C q values from 1 pL of the initial, unenriched sample with 1 pL of the sample undergoing enrichment.
  • the AC g between these two samples is used to determine the percentage of functional analytes collected at the end of the sample preparation process (i.e., the end-to-end efficiency).
  • airjet enrichment with methyl cellulose captured 85% of X-DNA in 1 pL volume from a 100 pL sample.
  • volume reduction by evaporation results in less than 10% of X-DNA in the 1 pL transferred volume.
  • the aiijet-enrichment method localizes the analyte underneath the nozzle for easy and efficient sample transfer, while evaporative volume reduction results in a uniformly spatial distribution within the remaining volume and suffers from the coffee-ring effect.
  • RNA is a frequently targeted analyte for detection but is more susceptible to degradation. Therefore, the collection efficiencies of HeLa-S3 RNA were evaluated alongside X-DNA to determine if airjet enrichment was equally effective (Figure 12B, panel c). Upon comparison, RNA results yielded consistently lower collection efficiencies averaging to 72%, while X-DNA exhibited a 92% average collection efficiency. The reduced efficiency observed for RNA may be attributed to temperature-dependent auto-hydrolysis caused by the heated aiijet. According to Figure 9B, the voltage of 3.5V used during RNA enrichment would yield a mild temperature profile (between 16 and 22 °C).
  • RNA enrichment generally yielded lower values, consistent with the findings in Figure 12B, panel c, and analyte loss occurred primarily during the small-volume enrichment stage.
  • Figure 13 shows data plots depicting a comparison of cumulative ACq (orange) and fold-enrichment (green) for X-DNA, HeLa-S3 RNA, and heat-inactivated SARS-CoV-2 in 0. ImM EDTA for solutions with PEG (+ PEG) (left data plot) and without PEG (- PEG) (right data plot).
  • PEG400 a non-volatile compound in which salts have reduced solubility
  • the double-stage enrichment was repeated with the same analytes spiked in a solution of 5% (v/v) PEG400 and 0. ImM EDTA.
  • EDTA is a chelator for divalent cations and a commonly used salt for RNA storage. However, it is also a PCR inhibitor at high concentrations as it sequesters the magnesium ions which are cofactors for polymerase activity. Co-enrichment of PEG400 was examined to the degree by which it could reduce the ACq and recover the signal during downstream analysis.
  • Figure 14 shows a data plot depicting the Cq vs. EDTA concentration for a solution of X-DNA in an example implementation of the disclosed technology. For each concentration, 1 pL from the EDTA solution was added to 9 pL of the qPCR reaction mix.
  • an airjet enrichment method in accordance with the present technology can concentrate analytes to aid in sample preparation and improve downstream detection sensitivity.
  • the method offers a direct and cost-effective approach, requiring only compressed air, a nozzle, and a surfactant to function for some embodiments.
  • aiijet enrichment relies on reversing the coffee-ring effect, various particles and molecules can be concentrated regardless of their physical and chemical properties.
  • the degree of enrichment was quantified using qPCR with X-DNA, HeLa-S3 RNA, and heat- inactivated SARS-CoV-2 acting as model analytes.
  • Example reagents used in example implementations of the devices, systems, and methods in accordance with the present technology include the following. Methyl cellulose (M7140), PEG400 (202398), and EDTA disodium salt (E5134) were obtained from MilliporeSigma. Carboxylate-modified lum beads (T8883), streptavidin conjugated quantum dots (Q10143MP), X-DNA (SD0011), and HeLa-S3 total RNA (AM7852) were obtained from Thermo-Fisher Scientific. Heat-inactivated SARS-CoV-2 (VR-1986HK) were obtained from ATCC.
  • FITC-labeled oligonucleotides and primers for X-DNA, BRACAf and NJ were synthesized by Integrated DNA Technologies (IDT).
  • IDCT Integrated DNA Technologies
  • iTaq Universal SYBR Green Supermix (1725120) and iTaq Universal SYBR Green One-Step Kit (1725150) were obtained from BioRad.
  • a borosilicate glass Pasteur pipette was separated into two halves. A coil from 40mm of 28-gauge nichrome wire was made and the ends were braided with electrical wire. After the coil was inserted into the pipette half, the other half was re-sealed using a heat-resistant ceramic adhesive. The ends of the wire were connected to an adjustable DC power supply (Tekpower TP1503C) during operation.
  • Tekpower TP1503C adjustable DC power supply
  • a thermal camera (FLIR A300) was used to capture thermal images for the nichrome heater and liquid in a 96-well plate.
  • a solution of dye and 50 pg/mL methyl cellulose in Ultrapure H2O was used as the bulk liquid and filled the well. The airflow rate and the voltages were adjusted accordingly. Three minutes were given to achieve steady state before taking the temperature profile.
  • the enrichment was performed until 1 mL evaporated off and a distinct layer of concentrated dye formed.
  • the enrichment in the 96-well plate was performed as previously described, adding 1 pL of 5 mg/mL methyl cellulose to the well to achieve spot enrichment.
  • 1 pL of the enriched sample was transferred to a qPCR reaction and compared with 1 pL of reference sample from the initial nucleic acid solution. Negatives were run simply based on evaporation, where the inner tube was not present for the large volume enrichment, and no methyl cellulose was present in the 96-well enrichment.
  • a method for sample enrichment includes distributing a plurality of particles in a solution under ambient evaporation; and applying a flow of gas through one or more aiijets to increase concentration of the plurality of particles in the solution.
  • Example 2 includes the method of example 1 or any of examples 1-16, wherein the flow of gas applied through the one or more airjets reverses radial flow by establishing a large evaporative flux at a center of a droplet of the solution.
  • Example 3 includes the method of example 1 or any of examples 1-16, wherein the flow of gas applied through the one or more airjets displaces a boundary layer comprised of saturated water vapor which lies directly above a liquid-air interface.
  • Example 4 includes the method of example 3 or any of examples 1-16, wherein displacement of the boundary layer leads to enhanced diffusion across the liquid-air interface and shifts an evaporative gradient towards an area under the one or more airjets.
  • Example 5 includes the method of any of examples 1-4 or any of examples 1-16, further comprising controlling an overall evaporation rate based at least on controlling temperature of the flow of gas through the one or more aiijets.
  • Example 6 includes the method of any of examples 1-5 or any of examples 1-16, further comprising controlling an overall evaporation rate based at least on controlling temperature of the solution.
  • Example 7 includes the method of any of examples 1-6 or any of examples 1-16, wherein the flow of gas applied through the one or more aiijets includes positioning a nozzle above a droplet of the solution and directing a jet of air perpendicular to its surface.
  • Example 8 includes the method of any of examples 1-7 or any of examples 1-16, wherein the gas includes at least one of nitrogen, argon, air, or a combination thereof.
  • Example 9 includes the method of any of examples 1-16, wherein the droplet is a sessile droplet.
  • Example 10 includes the method of any of examples 1-9 or any of examples 1-16, further comprising adding a surfactant to the solution before the applying the flow of gas though the one or more airjets.
  • Example 11 includes the method of example 10 or any of examples 1-16, wherein the surfactant includes one or more of methyl cellulose, polydimethyl siloxane, or sodium dodecyl sulfate.
  • Example 12 includes the method of any of examples 1-11 or any of examples 1-16, wherein the one or more aiijets are set up in parallel.
  • Example 13 includes the method of any of examples 1-11 or any of examples 1-16, wherein the one or more aiijets are set up in an array.
  • Example 14 includes the method of any of examples 1-11 or any of examples 1-16, wherein the one or more aiijets are aimed at the same location.
  • Example 15 includes the method of any of examples 1-11 or any of examples 1-16, wherein the one or more aiijets are aimed at more than one location.
  • Example 16 includes the method of any of examples 1-15, wherein the plurality of particles include one or more of nucleic acid molecules, polynucleotides, viruses, dissolved components, suspended components, or a combination thereof.
  • a method for sample enrichment includes distributing a plurality of particles in a solution under ambient evaporation; applying the solution to a porous membrane; and applying a flow of gas through one or more aiijets to increase concentration of the plurality of particles in the solution.
  • Example 18 includes the method of example 17 or any of examples 17-27, wherein the porous membrane includes one or more of paper, cotton, microfiber, bamboo, nitrocellulose, or a combination thereof.
  • Example 19 includes the method of any of examples 17-18 or any of examples 17-27, further comprising controlling an overall evaporation rate based at least on controlling temperature of the flow of gas through the one or more aiijets.
  • Example 20 includes the method of any of examples 17-19 or any of examples 17-27, further comprising controlling an overall evaporation rate based at least on controlling temperature of the solution.
  • Example 21 includes the method of any of examples 17-20 or any of examples 17-27, wherein the flow of gas applied through the one or more aiijets includes positioning a nozzle above the solution and directing a jet of air perpendicular to its surface.
  • Example 22 includes the method of any of examples 17-21 or any of examples 17-27, wherein the gas includes at least one of nitrogen, argon, air, or a combination thereof.
  • Example 23 includes the method of any of examples 17-22 or any of examples 17-27, wherein the one or more aiijets are set up in parallel.
  • Example 24 includes the method of any of examples 17-22 or any of examples 17-27, wherein the one or more aiijets are set up in an array.
  • Example 25 includes the method of any of examples 17-22 or any of examples 17-27, wherein the one or more aiijets are aimed at the same location.
  • Example 26 includes the method of any of examples 17-22 or any of examples 17-27, wherein the one or more aiijets are aimed at more than one location.
  • Example 27 includes the method of any of examples 17-26, wherein the plurality of particles include one or more of nucleic acid molecules, polynucleotides, viruses, dissolved components, suspended components, or a combination thereof.
  • a method for sample enrichment includes distributing a plurality of particles in a solution under ambient evaporation; applying the solution to a membrane, the membrane comprising (i) a first material comprising a porous material and (ii) a second material comprising a non-porous material or a second porous material having substantially less pores than the porous material of the first material; and creating a differential evaporation rate through airflow from one or more sources between one or more locations of the membrane to increase the concentration of the plurality of particles or dissolved or suspended components in the solution at locations on the membrane where the evaporation rate of the solution is greater.
  • Example 29 includes the method of example 28 or any of examples 28-40, wherein the porous material of the first material includes one or more of paper, cotton, microfiber, bamboo, nitrocellulose, or a combination thereof.
  • Example 30 includes the method of example 28 or any of examples 28-40, wherein the porous material of the first material is a cellulose-based material.
  • Example 31 includes the method of any of examples 28-30 or any of examples 28-40, wherein the porous material of the first material is thinner than the non-porous material or second porous material of the second material.
  • Example 32 includes the method of any of examples 28-31 or any of examples 28-40, wherein the airflow from the one or more sources between the one or more locations of the membrane are passive airflow sources.
  • Example 33 includes the method of any of examples 28-32 or any of examples 28-40, wherein the airflow from the one or more sources between the one or more locations of the membrane are active airflow sources.
  • Example 34 includes the method of any of examples 28-33 or any of examples 28-40, further comprising controlling an overall evaporation rate based at least on controlling temperature of the airflow.
  • Example 35 includes the method of any of examples 28-34 or any of examples 28-40, wherein a gas in the airflow includes at least one of nitrogen, argon, air, or a combination thereof.
  • Example 36 includes the method of any of examples 28-35 or any of examples 28-40, wherein the one or more sources of the airflow are set up in parallel.
  • Example 37 includes the method of any of examples 28-35 or any of examples 28-40, wherein the one or more sources of the airflow are set up in an array.
  • Example 38 includes the method of any of examples 28-35 or any of examples 28-40, wherein the one or more sources of the airflow are aimed at the same location.
  • Example 39 includes the method of any of examples 28-35 or any of examples 28-40, wherein the one or more sources of the airflow are aimed at more than one location.
  • Example 40 includes the method of any of examples 28-39, wherein the plurality of particles include one or more of nucleic acid molecules, polynucleotides, viruses, dissolved components, suspended components, or a combination thereof.
  • a device or system for sample enrichment includes an airjet-induced liquid phase enrichment technique operable to implement the method of any of examples 1-16, the method of any of examples 17-27, or the method of any of examples 28-40.
  • a device for sample enrichment includes one or more sources of airflow; a membrane; and a heating unit.
  • Example 43 includes the device of example 42 or any of examples 42-55, wherein the one or more sources of airflow further comprise an additional heating unit.
  • Example 44 includes the device of example 42 or 43 or any of examples 42-55, wherein the one or more sources of airflow include at least one airjet, wherein the at least one aiijet comprises a nozzle structure comprising two regions with the heating element interested in a middle zone of the two regions.
  • Example 45 includes the device of example 44 or any of examples 42-55, wherein the heating element includes a coil nichrome that is braided at its ends with wire leading outside the nozzle structure of the airjet.
  • Example 46 includes the device of any of examples 42-45 or any of examples 42-55, wherein the membrane is porous.
  • Example 47 includes the device of any of examples 42-45 or any of examples 42-55, wherein the membrane includes one or more of paper, cotton, microfiber, bamboo, nitrocellulose, or a combination thereof.
  • Example 48 includes the device of example 42 or 43 or any of examples 42-55, wherein the membrane comprises a first porous material and a second material that is a non- porous material or a less porous material than the first porous material.
  • Example 49 includes the device of example 48 or any of examples 42-55, wherein the first porous material includes at least one of paper, cotton, microfiber, bamboo, nitrocellulose, or a combination thereof.
  • Example 50 includes the device of any of examples 42-49 or any of examples 42-55, wherein the one or more sources of the airflow are set up in parallel.
  • Example 51 includes the device of any of examples 42-50 or any of examples 42-55, wherein the one or more sources of the airflow are set up in an array.
  • Example 52 includes the device of any of examples 42-50 or any of examples 42-55, wherein the one or more sources of the airflow are aimed at the same location.
  • Example 53 includes the device of any of examples 42-50 or any of examples 42-55, wherein the one or more sources of the airflow are aimed at more than one location.
  • Example 54 includes the device of any of examples 42-53 or any of examples 42-55, wherein the one or more sources of the airflow are passive.
  • Example 55 includes the device of any of examples 42-53 or any of examples 42-54, wherein the one or more sources of the airflow are active.
  • Example 55 includes the device of any of examples 42-55, wherein the device is configured to implement the method of any of examples 1-16, the method of any of examples 17-27, or the method of any of examples 28-40.
  • a device for sample enrichment includes one or more sources of airflow; a substrate, wherein the substrate is a non-porous material, and wherein the substrate includes a base and an exterior wall; a membrane, wherein the membrane comprises a first material comprising a porous material and a second material comprising a non-porous material or a less porous material than the first porous material, and wherein the first porous material is thinner than the second material; and one or more heating units, wherein the one or more heating units are attached to the substrate, the one or more sources of airflow, or a combination thereof.
  • Example 57 includes the device of example 56, wherein the device is configured to implement the method of any of examples 1-16, the method of any of examples 17-27, or the method of any of examples 28-40.
  • a “nucleic acid molecule” or “polynucleotide” refers to a polymeric compound including covalently linked nucleotides comprising natural subunits (e.g., purine or pyrimidine bases).
  • Purine bases include adenine, and guanine, and pyrimidine bases including uracil, thymine, and cytosine.
  • Nucleic acid molecules include polyribonucleic acid (RNA), polydeoxyribonucleic acid (DNA), which includes cDNA, genomic DNA, and synthetic DNA, either of which may be single or double-stranded.
  • a nucleic acid molecule encoding an amino acid sequence includes all nucleotide sequences that encode the same amino acid sequence.
  • any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated.
  • any number range of this disclosure relating to any physical feature, such as polymer subunits, size, or thickness are to be understood to include any integer within the recited range, unless otherwise indicated.
  • numerical ranges are inclusive of their recited endpoints, unless specifically stated otherwise.
  • Implementations of the subject matter and the functional operations described in this patent document can be implemented in various systems, digital electronic circuitry, or in computer software, firmware, or hardware, including the structures disclosed in this specification and their structural equivalents, or in combinations of one or more of them.
  • Implementations of the subject matter described in this specification can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a tangible and non-transitory computer readable medium for execution by, or to control the operation of, data processing apparatus.
  • the computer readable medium can be a machine- readable storage device, a machine-readable storage substrate, a memory device, a composition of matter effecting a machine-readable propagated signal, or a combination of one or more of them.
  • data processing unit or “data processing apparatus” encompasses all apparatus, devices, and machines for processing data, including by way of example a programmable processor, a computer, or multiple processors or computers.
  • the apparatus can include, in addition to hardware, code that creates an execution environment for the computer program in question, e.g., code that constitutes processor firmware, a protocol stack, a database management system, an operating system, or a combination of one or more of them.
  • a computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment.
  • a computer program does not necessarily correspond to a file in a file system.
  • a program can be stored in a portion of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to the program in question, or in multiple coordinated files (e.g., files that store one or more modules, sub programs, or portions of code).
  • a computer program can be deployed to be executed on one computer or on multiple computers that are located at one site or distributed across multiple sites and interconnected by a communication network.
  • the processes and logic flows described in this specification can be performed by one or more programmable processors executing one or more computer programs to perform functions by operating on input data and generating output.
  • the processes and logic flows can also be performed by, and apparatus can also be implemented as, special purpose logic circuitry, e.g., an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).
  • processors suitable for the execution of a computer program include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer.
  • a processor will receive instructions and data from a read only memory or a random access memory or both.
  • the essential elements of a computer are a processor for performing instructions and one or more memory devices for storing instructions and data.
  • a computer will also include, or be operatively coupled to receive data from or transfer data to, or both, one or more mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks.
  • mass storage devices for storing data, e.g., magnetic, magneto optical disks, or optical disks.
  • a computer need not have such devices.
  • Computer readable media suitable for storing computer program instructions and data include all forms of nonvolatile memory, media and memory devices, including by way of example semiconductor memory devices, e.g., EPROM, EEPROM, and flash memory devices.
  • semiconductor memory devices e.g., EPROM, EEPROM, and flash memory devices.
  • the processor and the memory can be supplemented by, or incorporated in, special purpose logic circuitry.

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Abstract

L'invention concerne des dispositifs, des systèmes et des procédés d'enrichissement amélioré d'échantillon. Selon certains aspects, une technique de préconcentration d'échantillon comprend un enrichissement en phase liquide induit par jet d'air. Dans d'autres aspects, une technique de préconcentration d'échantillon comprend un enrichissement en phase liquide par l'intermédiaire d'un gradient d'évaporation induit par un écoulement d'air passif ou actif.
PCT/US2024/028655 2023-05-09 2024-05-09 Systèmes, dispositifs et procédés d'enrichissement d'échantillon Pending WO2024233825A2 (fr)

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