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WO2011071551A1 - Cellule de prélèvement pour analyse de spectroscopie, systèmes et applications associés - Google Patents

Cellule de prélèvement pour analyse de spectroscopie, systèmes et applications associés Download PDF

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Publication number
WO2011071551A1
WO2011071551A1 PCT/US2010/023324 US2010023324W WO2011071551A1 WO 2011071551 A1 WO2011071551 A1 WO 2011071551A1 US 2010023324 W US2010023324 W US 2010023324W WO 2011071551 A1 WO2011071551 A1 WO 2011071551A1
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WO
WIPO (PCT)
Prior art keywords
sample cell
sample
windows
range
inner ridge
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
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PCT/US2010/023324
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English (en)
Inventor
Pieter Roos
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MOLECULAR BIOMETRICS Inc
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MOLECULAR BIOMETRICS Inc
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Publication of WO2011071551A1 publication Critical patent/WO2011071551A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information
    • B01L2300/021—Identification, e.g. bar codes
    • B01L2300/022—Transponder chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/168—Specific optical properties, e.g. reflective coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides

Definitions

  • sample cell When analyzing samples using spectroscopy, the samples are contained in a vessel which is commonly referred to as a sample cell or cuvette. These vessels typically contain two sides of optical quality material that allow radiation to pass through the sample.
  • sample cells Conventional sample cells are designed for large sample volumes, e.g., on the order of 30-100 microliters and are therefore unsuitable in situations where only small sample volumes are available, e.g., of 10 microliters or less.
  • the amount of radiation absorbed by a sample is proportional to the path length of the sample (i.e., the distance the radiation has to travel through the sample). Without innovative designs, small volumes lead to short path lengths and less sensitive measurements. It is therefore a challenge to retain high sensitivity while
  • the present disclosure provides a sample cell for spectroscopic analysis of fluid samples.
  • the sample cell has a body with windows that are located within recesses of upper and lower surfaces. The windows are spaced from the body surface.
  • An optical chamber passes through the body and is in fluid communication with feed conduits that include channel portions within the recesses.
  • the feed conduits each have an outlet on a surface of the body through which a fluid sample can be introduced into the optical chamber.
  • An inner ridge protrudes from within at least one of the recesses and surrounds the feed conduit. The inner ridge is spaced from its corresponding window.
  • the present disclosure also provides systems that include a sample cell and a spectrometer and uses of such systems.
  • Figure 1 shows an exemplary sample cell 10 in isometric, elevation, plan and cross- sectional view.
  • Figure 2 shows additional views of an exemplary sample cell 10, including optical chamber 12, feed conduit 70, ridges 40, 42, 44, circular support ring 50, support ribs 52, and windows 30, 32 and adhesive 100.
  • Figure 3 shows a cross section of an exemplary sample cell 10, illustrating the relationship between the optical chamber 12, body surfaces 14, 16, recesses 90, 92, feed conduit channel portions 70, 72, ridges 40, 42, 44 and windows 30, 32.
  • Figure 4 shows a detailed end cross section of an exemplary sample cell 10, including feed conduit outlet 62, feed conduit 22 with channel portion 72, body surfaces 14, 16 and recesses 90, 92.
  • the design needs to take into account the wavelength of light used (e.g., UV, visible, infrared, etc.), the sensitivity of the spectrometer and the nature of the spectroscopic technique (e.g., absorption, scattering, etc.).
  • the wavelength of light used e.g., UV, visible, infrared, etc.
  • the sensitivity of the spectrometer e.g., the sensitivity of the spectrometer
  • the nature of the spectroscopic technique e.g., absorption, scattering, etc.
  • the present disclosure provides a sample cell that results from efforts to produce a design that can handle small sample volumes while minimizing the presence of air bubbles.
  • the sample cell has a body with windows that are located within recesses of upper and lower surfaces. The windows are spaced from the body surface.
  • An optical chamber passes through the body and is in fluid communication with feed conduits that include channel portions within the recesses.
  • the feed conduits each have an outlet on a surface of the body through which a fluid sample can be introduced into the optical chamber.
  • An inner ridge protrudes from within at least one of the recesses and surrounds the feed conduit. The inner ridge is spaced from its corresponding window.
  • the reduction of air bubbles in the optical chamber is thought to result from the inclusion of the inner ridge and a small gap between the inner ridge and its corresponding window.
  • This design feature stemmed from the recognition that the differences in surface tension of the fluid sample and air with the surfaces and materials of the sample cell could be used to preferentially allow air bubbles to flow over, and become trapped behind, the inner ridge.
  • the components of an exemplary sample cell are shown in Figures 1-4.
  • the gap between inner ridge 40 and windows 30, 32 is most readily visible in Figure 3. In various embodiments, the gap may range from about 0.01 mm to about 0.25 mm.
  • the gap may range from about 0.01 mm to about 0.05 mm, e.g., from about 0.01 mm to about 0.04 mm, from about 0.01 mm to about 0.03 mm, or from about 0.01 mm to about 0.02 mm.
  • the gap is such that air passes through the gap more easily than the fluid sample to be tested (e.g., any of the fluid samples discussed herein including embryo culture media, amniotic fluid, blood, etc.).
  • the gap is achieved by having an inner ridge 40 with a height lower than the height of a support means for windows 30, 32.
  • the support means comprises one or more raised structures located within the recesses. For example, as shown in Figures 1-4 one or more outer ridges 42, 44, a circular support ring 50, and/or support ribs 52 may form part of a support means.
  • the one or more outer ridges 42, 44 may also serve to contain any fluid sample that leaks over the inner ridge.
  • the one or more outer ridges 42, 44 may further serve to seal the fluid sample and optical chamber 12 from portions of recesses 90, 92 (e.g., to prevent adhesive 100 from mixing with the fluid sample and/or entering the optical chamber 12).
  • inner ridge 40 is generally, but not necessarily, perpendicular to the body surfaces 14, 16 from which it protrudes. In general, inner ridge 40 surrounds the channel portion 70, 72 of feed conduits 20, 22 and one end of optical chamber 12.
  • the height of inner ridge 40 may be any height within the limits of the manufacture and machining of the material of construction of sample cell 10.
  • inner ridge 40 has a height in the range of about 0.05 mm to about 0.25 mm. In some of these embodiments, inner ridge 40 has a height of at least about 0.07 mm, 0.09 mm, 0.1 1 mm, 0.13 mm, or 0.15 mm. In other embodiments, inner ridge 40 has a height of less than about 0.15 mm, 0.13 mm, 0.1 1 mm, 0.09 mm, or 0.07 mm. In any of these embodiments, the height of inner ridge 40 is not necessarily constant along its length. The horizontal distance between the edge of channel portions 70, 72 and the centerline of inner ridge 40 may also vary along its length and may be any distance within the range of manufacture and machining of the material of construction of the sample cell.
  • the distance is in the range of about 0.05 mm to about 2 mm (e.g., at least about 0.05 mm, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 1 mm, or 2 mm).
  • the one or more outer ridges 42, 44 are also generally, but not necessarily, perpendicular to body surfaces 14, 16 from which they protrude.
  • the one or more outer ridges 42, 44 surround inner ridge 40.
  • the inner and outer ridges may merge at one or more points.
  • the height of the one or more outer ridges may be any height within the limits of the method of manufacture and machining of the material of construction of sample cell 10. It is to be understood that the heights of the one or more outer ridges 42, 44 may be the same or different and that they may not be constant along their lengths.
  • the one or more outer ridges 42, 44 have a height in the range of about 0.05 mm to about 0.25 mm.
  • they have a height of at least about 0.07 mm, 0.09 mm, 0.1 1 mm, 0.13 mm, 0.15 mm or 0.20 mm. In other embodiments, they have a height of less than about 0.20 mm, 0.15 mm, 0.13 mm, 0.11 mm, 0.09 mm, or 0.07 mm.
  • the outer ridge 42 that is closest to inner ridge 40 is of approximately the same height as inner ridge 40 (i.e., it is also spaced from the corresponding window). In other embodiments, the outer ridge 42 that is closest to inner ridge 40 is taller than inner ridge 40 and contacts the corresponding window.
  • sample cell 10 includes two outer ridges 42, 44 as shown in Figures 1-4 and both outer ridges 42, 44 are taller than inner ridge 40 and contact the corresponding window. It is to be understood that the sample cell of the present disclosure is not limited to the aforementioned structures, and that the present disclosure encompasses the use of additional structures and ridges as well as alternative geometries and orientations of ridges in a sample cell 10. The distance between any of the ridges (i.e., between inner and outer ridges and between outer ridges) may be within the limits of manufacture and machining of the materials of construction of the sample cell 10.
  • each ridge and windows 30, 32, edges of channels portions 70, 72 or the central axis of optical chamber 12 need not be equal or constant and may vary independently. Additionally, the distances between any of the ridges (e.g., ridges 40, 42, 44) may vary independently.
  • sample cell 10 includes an optical chamber 12.
  • the optical chamber passes through the body 80 of sample cell 10 and exits into recesses 90, 92.
  • Optical chamber 12 can be any cross-sectional shape including circular, oval, square, rectangular, etc.
  • the optical chamber 12 is cylindrical.
  • recesses 90, 92 are designed to accommodate windows 30, 32.
  • the dimensions of optical chamber 12 can be determined to minimize total sample volume, maximize sensitivity during analysis, and accommodate particular radiation wavelengths and radiation beam profiles.
  • the diameter or cross-sectional area of the optical chamber 12 may be selected so that radiation having the wavelength(s) of interest can propagate through optical chamber 12.
  • the length of the chamber will generally be chosen so that it generates consistent results with radiation having the wavelength(s) of interest. It will be appreciated that these dimensions may also need to be adjusted depending on the nature of the fluid sample (e.g., the water content of the fluid sample can dramatically affect infrared absorption levels). These two dimensions then determine the volume of optical chamber 12 and thus have an impact on the fluid sample volume required to fill the optical chamber 12. For certain fluid samples it will be desirable to minimize sample volume due to limited availability of the sample or because the sample is hazardous.
  • optical chamber 12 has a volume in the range of about 2 microliters to about 30 microliters (e.g., about 2 microliters to about 10 microliters, about 2 microliters to about 30 microliters, or about 2 microliters to about 5 microliters).
  • the optical chamber has a diameter or cross-section in the range of about 0.5 mm to about 2 mm (e.g., about 0.75 mm to about 1.25 mm, or about 1 mm).
  • the optical chamber has an optical path length in the range of about 1 mm to about 10 mm (e.g., about 3 mm to about 7 mm, about 4 mm to about 8 mm).
  • the sample cell is only able to accommodate a fluid sample with a volume in the range of about 3 microliters to about 40 microliters (e.g., up to about 40 microliters, 35 microliters, 30 microliters, 25 microliters, 20 microliters, 15 microliters, 10 microliters, or 5 microliters).
  • sample cell 10 can be constructed from any material of construction that is compatible with the fluid sample to be analyzed and the spectroscopic technique being employed. In various embodiments, the material does not absorb the radiation (e.g., infrared radiation) that is used in the spectroscopic technique. In various embodiments, sample cell 10 is made of a moldable material. In various embodiments, sample cell 10 is made of acrylonitrile butadiene styrene (ABS). ABS does not absorb infrared radiation and is therefore particularly suitable for spectroscopic analyses that use infrared radiation. In other embodiments, sample cell 10 is made of TEFLON, polypropylene, aluminum, etc.
  • ABS acrylonitrile butadiene styrene
  • Sample cell 10 includes windows 30, 32 within recesses 90, 92.
  • Recesses 90, 92 can be of any depth within the limitations of manufacturing or machining the material of construction. In various embodiments, each recess has a depth in the range of about 0.5 mm to about 2 mm.
  • body 80 of sample cell 10 is not necessarily a single block of material, but can be constructed by combining two or more blocks of material. It will also be appreciated that body 80 of sample cell 10 is not necessarily a solid block of material and can include various structures, e.g., indentations, protrusions, grooves, ridges, etc. beyond those that are explicitly described herein and in Figures 1-4.
  • Windows 30, 32 are positioned within recesses 90, 92 to enclose optical chamber 12 and adjacent areas of the recess.
  • windows 30, 32 and recesses 90, 92 are circular.
  • windows 30, 32 and recesses 90, 92 are non-circular (e.g., square, rectangular, elliptical, etc.).
  • recesses 90, 92 have dimensions (e.g., diameters) that are larger than the dimensions of windows 30, 32.
  • Each window can be supported by any support means.
  • the support means includes, one or more support ribs 52, one or more outer ridges 42, 44, or any combination of these raised structures.
  • an outer ridge may be in the form of a circular support ring 50 (optionally at the periphery of recess 90, 92).
  • the interface of the raised structure(s) and windows effect to seal optical chamber 12.
  • windows 30, 32 are secured to body surfaces 14, 16 of sample cell 10. Any securing means may be used for that purpose (e.g., pressure fit, snap fit, adhesive, etc.).
  • windows 30, 32 may be secured using adhesive 100 within recesses 90, 92.
  • adhesive 100 is a glue, e.g., an instant cure glue or a UV curable glue. In general, it will be desirable to place adhesive 100 outside inner ridge 40.
  • adhesive 100 may be located on the outside of outer ridges 42, 44.
  • outer ridges 42, 44 may act as a barrier that prevents adhesive 100 from mixing with the fluid sample and entering into optical chamber 12.
  • outlets 60, 62 are located on the same body surface. In various embodiments, outlets 60, 62 are located on a surface of the body that is located between upper and lower body surfaces 14, 16 (e.g., as shown in Figure 2). In various embodiments, outlets 60, 62 are located on different body surfaces, e.g., opposing body surfaces of sample cell 10. In any of these embodiments, outlets 60, 62 may be located in the same plane. In certain embodiments, outlets 60, 62 may be located in a plane that passes through the midsection of sample cell body 80.
  • outlets 60, 62 are circular and have a diameter in the range of about 0.5 mm to about 2 mm. In various embodiments, outlets 60, 62 are sized to accommodate the insertion of a pipette tip, e.g., a standard gel loading pipette tip.
  • Feed conduits 20, 22 also include channel portions 70, 72 within recesses 90, 92. In various embodiments and as shown in Figures 1-4, channel portions 70, 72 may comprise an arcuate loop before terminating at one end of optical chamber 12. Without being bound by any theory, the arcuate loop in channel portions 70, 72 is thought to induce a vortex in the fluid sample so that air is swept away from optical chamber 12, thereby reducing the risk of air bubbles blocking optical chamber 12.
  • channel portions 70, 72 can also be linear and can additionally or alternatively include linear or curvilinear sections. It is also to be understood that the cross-sectional shape of channels portions 70, 72 can be any shape (e.g., rectangular, square, elliptical, semicircular, etc.). In various embodiments, the feed conduits within upper and lower surfaces 14, 16 are mirror images of each other as shown in Figures 1-4.
  • the windows are made of calcium fluoride, borosilicate glass, sapphire optical glass, quartz, poly(methyl methacrylate), polystyrene, poly(carbonate), or an acrylic styrene methyl methacrylate copolymer (e.g., from the NAS polymer series). In various embodiments, the windows are made of calcium fluoride.
  • a scattering material is used in at least one windows 30, 32.
  • the scattering material is a fluoropolymer (e.g., TEFLON, etc.).
  • a reflective material or coating e.g., aluminum is used for the sample cell, or for lining the optical chamber 12. Without being bound by any theory, the scattering of light may increase the interaction between the radiation and the fluid sample contained in optical chamber 12.
  • the present disclosure provides systems that include a sample cell 10 and a spectrometer.
  • spectrometer encompasses any device that is capable of generating and transmitting radiation through a fluid sample in the optical chamber 12 of the sample cell 10 and measuring the amount of radiation that is absorbed or reflected by the fluid sample at one or more wavelengths.
  • the present disclosure is in no way limited to any particular wavelength(s) or type of spectroscopy.
  • the spectrometer may include a source of radiation, a sample cell holder, a detector, and a means for computing the amount of radiation absorbed or reflected by the fluid sample (e.g., a processor that controls the source of radiation and processes signals from the detector in order to compute the amount of radiation absorbed or reflected by the fluid sample).
  • the system also includes a means for outputting and/or displaying the amount of radiation absorbed or reflected by the fluid sample at one or more wavelengths (e.g., a computer screen).
  • the spectrometer operates within the infrared spectrum. In various embodiments, the spectrometer operates within the near-infrared spectrum, e.g., within the range of about 700 nm to about 2200 nm or about 700 nm to about 1400 nm.
  • the system includes a temperature controlled heating block for storing sample cell 10 prior to spectroscopic analysis. In various embodiments, the region of the sample cell holder within the spectrometer is also temperature controlled. The temperatures of the heating block and sample cell holder may be the same or different.
  • the system may also include a suction means for removing a fluid sample from sample cell 10 such as a pump with a connection (e.g., a pipette tip) that can be placed into fluid communication with one of the outlets of feed conduits 60, 62.
  • a suction means for removing a fluid sample from sample cell 10 such as a pump with a connection (e.g., a pipette tip) that can be placed into fluid communication with one of the outlets of feed conduits 60, 62.
  • a fluid sample is introduced into sample cell 10 via one of the outlets 60, 62 of feed conduits 20, 22.
  • the term "fluid sample” includes, without limitation, a homogeneous solution or heterogeneous mixture which may be a liquid, suspension or gel. Any fluid sample may be used in accordance with the present disclosure.
  • effluent liquids from various sources laboratory samples for different purposes including forensic and biological samples may be used (e.g., cell or viral lysates, cell culture media, cell culture components, blood, blood products, blood components, lymph, mucus secretions, saliva, semen, amniotic fluid, follicular fluid, sweat, urine, cerebrospinal fluid, serum, plasma, tears, reconstituted lyophilized feces, etc.).
  • the fluid sample can be introduced into sample cell 10 by any means, e.g., using a syringe, a pipette with a pipette tip that fits within the outlet, a tube, etc.
  • sample cell 10 is empty when the fluid sample is introduced. Once introduced into a feed conduit, the fluid sample flows via the feed conduit into the channel portion, then through optical chamber 12 and on into the other feed conduit. In various embodiments, the volume of the fluid sample is less than the total volume of the sample cell so that feed conduits 20, 22 are not entirely filled with fluid sample. In various embodiments, the volume of the fluid sample is at least sufficient to fill optical chamber 12 and a portion of both feed conduits 20, 22. In various embodiments, sample cell 10 is stored in a temperature controlled heating block prior to spectroscopic analysis. It will be appreciated that the temperature of the heating block will depend on the type of fluid sample and type of spectroscopy.
  • the sample cell holder of the spectrometer may also be temperature controlled at the same or a different temperature.
  • the temperature of the sample cell holder is slightly lower (e.g., about 0.2 C to about 0.9 C lower, about 0.3 C to about 0.5 C lower, or about 0.4 lower).
  • sample cell 10 is placed within the sample cell holder of the spectrometer for spectroscopic analysis.
  • the source of radiation (which may include filters, etc.) produces a narrow beam of radiation (e.g., about 0.3 micrometers to about 0.5 micrometers in diameter).
  • the source of radiation and sample cell holder are designed such that the windows 30, 32 of the sample cell 10 are approximately perpendicular to the beam and the central axis of the beam is approximately aligned with the central axis of the optical chamber 12 (e.g., less than a 0.2 micrometer offset).
  • the spectrometer detector is located across from the source of radiation, on the opposite side of sample cell 10 and in alignment with the beam.
  • the sample cell 10 is removed from the sample cell holder.
  • the sample cell 10 is reused with a different fluid sample, e.g., a control sample.
  • a different fluid sample e.g., a control sample.
  • the second fluid sample may be introduced into the sample cell in the same manner as the first fluid sample.
  • the first fluid sample is flushed out of the sample cell using an excess volume of the second fluid sample. Depending on the type of fluid sample and the pressures involved, this approach may lead to leaks within the sample cell.
  • the first fluid sample may be removed by any means.
  • the first fluid sample may be removed from the sample cell using a suction means (i.e., a device such as a pump that is capable of generating a negative pressure gradient away from the sample cell and that can be connected to one of the outlets 60, 62 of feed conduits 20, 22).
  • the suction means may generate a low pressure in the range of about 0.2 atmospheres to about 0.4 atmospheres (e.g., about 0.25 atmospheres to about 0.3 atmospheres).
  • a system of the present disclosure may be used for the compositional analysis of one or more fluid samples (e.g., a test sample, fractions of a test sample obtained by chromatographic separation, etc.).
  • compositional analysis involves identifying specific molecular markers within a fluid sample. It is to be understood that these methods do not necessarily require the identity of the marker to be known (e.g., in various embodiments, a marker may be identified based on the presence of characteristic peak(s) in the spectrum without determining the identity of the marker). It will be appreciated that
  • compositional analyses may be performed using any spectroscopic technique that is capable of identifying the marker(s) in question. Without limitation, these may include single or multiwavelength optical absorption, Raman scattering, optical fluorescence, etc. and any combination thereof. In various embodiments, optical absorption may be within the infrared range (e.g., near-infrared range). In various embodiments, a chromatographic technique such as HPLC may be combined with one or more of these spectroscopic techniques. In various embodiments, the system may be capable of performing two or more different compositional analyses on any given fluid sample (e.g., using two or more different spectroscopic techniques for identifying the marker(s) of interest).
  • a system of the present disclosure may be used for the spectral analysis of one or more fluid samples (e.g., a test sample, fractions of a test sample obtained by chromatographic separation, etc.).
  • spectral analysis involves making correlations based on spectra of samples without necessarily identifying the specific molecules that are responsible for spectral features in a given sample.
  • correlations may be made using information from an entire spectrum.
  • correlations may be made using information from one or more regions of a spectrum (e.g., one or more wavelength regions in a spectrum, one or more wavelengths in a spectrum, etc.).
  • spectral analyses may be performed using any spectroscopic technique that is capable of producing a spectrum of the sample in question. Without limitation, these may include single or multiwavelength optical absorption, Raman scattering, optical fluorescence, etc. and any combination thereof. In various embodiments, optical absorption may be within the infrared range (e.g., near-infrared range). In various embodiments, a chromatographic technique such as HPLC may be combined with one or more of these spectroscopic techniques. In various embodiments, the system may be capable of performing two or more different spectral analyses on any given fluid sample (e.g., using two or more different spectroscopic techniques).
  • methods of the present disclosure may involve both a spectral analysis and a composition analysis of one or more samples.
  • spectral analysis may be used as an initial sample filter followed by a secondary compositional analysis of samples that satisfy the requirements of the spectral filter.
  • spectral analysis may be used as a secondary filter following a primary compositional analysis.
  • the methods may involve subjecting each sample to both a spectral analysis and a composition analysis.
  • the methods are executed as part of an assisted reproductive procedure, including in vitro fertilization.
  • an assisted reproductive procedure including in vitro fertilization.
  • 20070160973 describes systems and methods which employ spectral analysis of certain fluid samples in order to make predictions about the state of different types of cells involved in in vitro fertilization, including embryos, spermatozoa, oocytes, cells from the uterine wall, etc.
  • U.S. Patent Publication No. 20070160973 and any other publication referred to herein is hereby incorporated by reference in its entirety.
  • the fluid samples are taken from fluids that are exchanging metabolites with the cell(s) in question.
  • a correlation is initially established between the state of a particular type of cell and spectra of a fluid obtained using a chosen analytical modality for a population of cells with known outcome. For the cell being analyzed, a spectrum of the relevant fluid is obtained using the chosen modality.
  • the spectral analysis involves obtaining and then analyzing spectra of body fluids and/or gamete or embryo culture media used in in vitro fertilization procedures.
  • the methods involve predicting the viability of an oocyte based on spectral analysis of follicular fluid or culture media.
  • the methods involve predicting the viability of spermatozoa based on spectral analysis of seminal plasma or culture media.
  • the methods involve predicting the viability of an embryo based on the spectral analysis of culture media.
  • the spectral analysis is performed using single or multiwavelength optical absorption, Raman scattering or optical fluorescence.
  • optical absorption may be within the infrared range (e.g., near-infrared range).
  • the methods may involve determining one or more of: a time to transfer an embryo into a uterus; a time to subject an embryo to short term storage for future transfer into a uterus; a time to subject an embryo to cryopreservation for future transfer into a uterus; an adjustment to the culture medium to continue growing of an embryo; and a time to transfer an embryo into a different culture medium to continue growing of the embryo.
  • the methods are executed as part of a medical diagnostic or prognostic procedure.
  • U.S. Patent Publication No. 20070054347 describes systems and methods which employ spectral analysis of certain fluids in order to make diagnostic and prognostic predictions about various diseases.
  • a correlation is initially established between a particular diagnosis or prognosis and spectra of a fluid obtained using a chosen analytical modality for a population of patients with known diagnosis or prognosis.
  • a spectrum of the relevant fluid is obtained using the chosen modality.
  • the diagnosis or prognosis for the patient is then predicted using the acquired spectrum and the established correlation.
  • the spectral analysis involves obtaining and then analyzing spectra of body fluids (e.g., whole blood, blood plasma, blood serum, cerebrospinal fluid, etc.).
  • the spectral analysis is performed using single or multiwavelength optical absorption, Raman scattering or optical fluorescence.
  • optical absorption may be within the infrared range (e.g., near-infrared range).
  • the methods may involve prognostic predictions (e.g., predicting the likelihood that a patient will respond to a particular type of therapy).
  • the methods involve predicting the likelihood that a patient has Mild Cognitive Impairment (MCI).
  • MCI Mild Cognitive Impairment
  • the methods involve predicting the likelihood that a patient has Alzheimer's Disease. In various embodiments, the methods involve predicting the likelihood that a patient has Vascular Cognitive Impairment (VCI). In various embodiments, the methods involve predicting the likelihood that a patient has Parkinson's Disease. It is to be understood that these methods may also be applied outside the realm of these exemplary diseases.
  • U.S. Patent Publication No. 20060247536 describes methods and systems which employ spectral analysis of amniotic fluid in order to make predictions about the health of a mother and her fetus during pregnancy. Thus, in various embodiments, spectral analysis of amniotic fluid may be used to make predictions about fetal growth and the likely birth weight of the infant.
  • Patent Publication No. 20060247536 also describes compositional analytical methods and systems that use specific molecular markers in amniotic fluid in order to make predictions about the health of a mother and her fetus during pregnancy. Thus, in various embodiments, these markers may be used to make predictions about the likelihood that the mother will develop Gestational Diabetes Mellitus (GDM).
  • GDM Gestational Diabetes Mellitus

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Optical Measuring Cells (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

La présente invention concerne une cellule de prélèvement pour l'analyse par spectroscopie d'échantillons de fluides. La cellule de prélèvement présente un corps doté de fenêtres qui sont situées dans des renfoncements des surfaces supérieure et inférieure. Les fenêtres sont espacées de la surface du corps. Une chambre optique passe à travers le corps et est en communication fluidique avec des conduits d'alimentation qui comprennent des parties profilées en U au sein des renfoncements. Les conduites d'alimentation ont chacune un orifice de sortie sur une surface du corps à travers lequel un échantillon de fluide peut être introduit dans la chambre optique. Une arête interne fait saillie d'au moins un des renfoncements et entoure la conduite d'alimentation. L'arête interne est espacée de sa fenêtre correspondante. La présente invention concerne également des systèmes qui comprennent une cellule de prélèvement et un spectromètre ainsi que les applications desdits systèmes.
PCT/US2010/023324 2009-12-08 2010-02-05 Cellule de prélèvement pour analyse de spectroscopie, systèmes et applications associés Ceased WO2011071551A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8323177B2 (en) 2009-08-22 2012-12-04 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US9482659B2 (en) 2010-09-27 2016-11-01 Progyny, Inc. Apparatus, method, and system for the automated imaging and evaluation of embryos, oocytes and stem cells
US9879307B2 (en) 2011-02-23 2018-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods of detecting aneuploidy in human embryos
US10241108B2 (en) 2013-02-01 2019-03-26 Ares Trading S.A. Abnormal syngamy phenotypes observed with time lapse imaging for early identification of embryos with lower development potential
US11627728B2 (en) * 2017-02-23 2023-04-18 Ryshens Ltd. Devices and methods for determining analytes

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US5139333A (en) * 1988-11-11 1992-08-18 Automatik Apparate-Maschinebau Gmbh Measuring cell for the spectral analysis of flowing media, in particular plastic melts
US6188474B1 (en) * 1998-05-13 2001-02-13 Bayer Corporation Optical spectroscopy sample cell
US6983177B2 (en) * 2003-01-06 2006-01-03 Optiscan Biomedical Corporation Layered spectroscopic sample element with microporous membrane

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Publication number Priority date Publication date Assignee Title
US5139333A (en) * 1988-11-11 1992-08-18 Automatik Apparate-Maschinebau Gmbh Measuring cell for the spectral analysis of flowing media, in particular plastic melts
US6188474B1 (en) * 1998-05-13 2001-02-13 Bayer Corporation Optical spectroscopy sample cell
US6983177B2 (en) * 2003-01-06 2006-01-03 Optiscan Biomedical Corporation Layered spectroscopic sample element with microporous membrane

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8323177B2 (en) 2009-08-22 2012-12-04 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US8337387B2 (en) 2009-08-22 2012-12-25 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US8721521B2 (en) 2009-08-22 2014-05-13 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US8951184B2 (en) 2009-08-22 2015-02-10 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US8989475B2 (en) 2009-08-22 2015-03-24 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US9228931B2 (en) 2009-08-22 2016-01-05 The Board Of Trustees Of The Leland Stanford Junior University Imaging and evaluating embryos, oocytes, and stem cells
US9482659B2 (en) 2010-09-27 2016-11-01 Progyny, Inc. Apparatus, method, and system for the automated imaging and evaluation of embryos, oocytes and stem cells
US9879307B2 (en) 2011-02-23 2018-01-30 The Board Of Trustees Of The Leland Stanford Junior University Methods of detecting aneuploidy in human embryos
US10241108B2 (en) 2013-02-01 2019-03-26 Ares Trading S.A. Abnormal syngamy phenotypes observed with time lapse imaging for early identification of embryos with lower development potential
US11627728B2 (en) * 2017-02-23 2023-04-18 Ryshens Ltd. Devices and methods for determining analytes

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