Method and apparatus for the delivery of samples to a chemical sensor array

• US 6,713,298 B2
• Filed: 01/31/2001
• Issued: 03/30/2004
• Est. Priority Date: 01/31/2000
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Neikirk, Dean P., Anslyn, Eric V., McDevitt, John T., Shear, Jason B.
• Primary Examiner(s): STEELE, AMBER D
• Assistant Examiner(s): STEELE, AMBER D
• Application Number:
  US09/775,048
• Publication Number:
  US 20020045272A1
• Time in Patent Office: 1,154 Days
• Field of Search: 422/68.1, 422/67, 422/28.07, 422/55, 422/58, 435/6, 435/7.1, 435/286.1, 435/287.1, 435/287.8, 435/288.2, 435/288.4, 436/518, 436/531
• US Class Current: 435/287.8
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0657 Pipetting powder
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/049 vacuum
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 3/0289 Apparatus for withdrawing or distributing predetermined quantities of fluid B01L3/02 takes precedence; sample taking G01N1/00; sample taking within automatic analysers G01N35/00; volume measuring in general G01F
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/5027 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C12Q 1/34 : involving hydrolase
• CPC Class Codes: C12Q 1/37 : involving peptidase or proteinase
• CPC Class Codes: C40B 40/00 : Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: G01N 2001/021 : Correlating sampling sites with geographical information, e.g. GPS
• CPC Class Codes: G01N 2021/6417 : Spectrofluorimetric devices
• CPC Class Codes: G01N 2021/6421 : Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6432 : Quenching
• CPC Class Codes: G01N 2021/6439 : with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6441 : with two or more labels
• CPC Class Codes: G01N 2021/6482 : Sample cells, cuvettes
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/00564 : Handling or washing solid phase elements, e.g. beads
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/6454 : using an integrated detector array
• CPC Class Codes: G01N 21/6458 : Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G01N 21/6486 : Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 21/77 : by observing the effect on a chemical indicator
• CPC Class Codes: G01N 2201/062 : LED's
• CPC Class Codes: G01N 2201/0627 : Use of several LED's for spectral resolution
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y02A 90/10 : Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
• CPC Class Codes: Y10S 977/924 : using nanostructure as support of dna analysis
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A system for the rapid characterization of multi-analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member into which a plurality of cavities may be formed. A series of chemically sensitive particles are, in one embodiment positioned within the cavities. The particles may be configured to produce a signal when a receptor coupled to the particle interacts with the analyte. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized.

Claims

1. A system for detecting an analyte in a fluid comprising:

a light source;

a sensor array, the sensor array comprising a support layer, a spacer layer, a sensor layer and a cover layer, wherein the spacer layer is disposed upon at least a portion of the support layer, and wherein the sensor layer is disposed upon the spacer layer such that a first channel is formed between the sensor layer and the support layer, and wherein at least one cavity is formed within the sensor layer, and wherein the cavity is configured to allow at least a portion of the fluid to pass through the cavity during use, and wherein the cover layer is positioned above the sensor layer at a distance above the sensor layer such that the cover layer substantially inhibits the dislodgement of the particle from the cavity during use, and wherein the cover layer defines a second channel between the sensor layer and the cover layer such that the fluid passes through the second channel during use;

a particle, the particle positioned within the cavity, wherein the particle is configured to produce a signal when the particle interacts with the analyte during use; and

a detector, the detector being configured to detect the signal produced by the interaction of the analyte with the particle during use;

wherein the light source and detector are positioned such that light passes from the light source, to the particle, and onto the detector during use.

2. The system of claim 1, wherein the sensor layer comprises a plurality of particles positioned within a plurality of cavities, and wherein the system is configured to substantially simultaneously detect a plurality of analytes in the fluid.

3. The system of claim 1, wherein the support layer comprises glass.

4. The system of claim 1, wherein the support layer comprises a plastic material.

5. The system of claim 1, wherein the support layer comprises a dry film photoresist material.

6. The system of claim 1, wherein the spacer layer supports the outer portion of the sensor layer.

7. The system of claim 1, wherein the sensor layer comprises silicon.

8. The system of claim 1, further comprising a fluid inlet and a fluid outlet, wherein the fluid inlet is coupled to the cover layer, and wherein the fluid inlet is configured to allow the transfer of fluids through the cover layer to the second channel during use, and wherein the fluid outlet is coupled to the first channel, and wherein the fluid outlet is configured to allow the transfer of fluids from the first channel through the support layer during use.

9. The system of claim 1, wherein portions of the first and second channels are coated with a hydrophilic material.

10. The system of claim 1, wherein portions of the first and-second channels are coated with a hydrophobic material.

11. The system of claim 1, wherein portions of the first and second channels are coated with a hydrophilic material, and wherein portions of the first and second channels are coated with a hydrophobic material.

12. The system of claim 1, wherein a portion of the second channel is coated with a hydrophobic compound, such that the hydrophobic portion of the second channel is configured to capture air bubbles during use.

13. The system of claim 1, wherein the sensor layer comprises a plurality of particles positioned within a plurality of cavities, and wherein the system is configured to substantially simultaneously detect a plurality of analytes in the fluid.

14. The system of claim 1, wherein the light source comprises a light emitting diode.

15. The system of claim 1, further comprising a fluid delivery system coupled to the supporting member.

16. The system of claim 1, wherein the detector comprises a charge-coupled device.

17. The system of claim 1, wherein the particle ranges from about 0.05 micron to about 500 microns.

18. The system of claim 1, wherein a volume of the particle changes when contacted with the fluid.

19. The system of claim 1, wherein the particle comprises a receptor molecule coupled to a polymeric resin.

20. The system of claim 1, wherein the particle comprises a receptor molecule coupled to a polymeric resin, and wherein the polymeric resin comprises polystyrene-polyethylene glycol-divinyl benzene.

21. The system of claim 1, wherein the particle comprises a receptor molecule coupled to a polymeric resin, and wherein the particles further comprises a first indicator and a second indicator, the first and second indicators being coupled to the receptor, wherein the interaction of the receptor with the analyte causes the first and second indicators to interact such that the signal is produced.

22. The system of claim 1, wherein the particle comprises a receptor molecule coupled to a polymeric resin, and wherein the particles further comprises an indicator, wherein the indicator is associated with the receptor such that in the presence of the analyte the indicator is displaced from the receptor to produce the signal.

23. The system of claim 1, wherein first portions of the first and second channels are coated with a hydrophilic material, and wherein second portions of the first and second channels are coated with a hydrophobic materials, and wherein the first portions and the second portions are on opposing surfaces of the first and second channels.

24. The system of claim 1, wherein an inner surface of the cavity is coated with a material to increase adhesion of the particle to the inner surface of the cavity.

25. The system of claim 1, wherein an inner surface of the cavity is coated with a material to increase reflectivity of the inner surface of the cavity.

26. The system of claim 1, wherein the detector comprises an optical detector, wherein the optical detector is formed on a bottom surface of the supporting member below the cavity.

27. The system of claim 1, wherein the cavity is substantially tapered such that the width of the cavity narrows in a direction from a top surface of the supporting member toward a bottom surface of the supporting member, and wherein a minimum width of the cavity is substantially less than a width of the particle.

28. The system of claim 1, wherein a width of a bottom portion of the cavity is substantially less than a width of a top portion of the cavity, and wherein the width of the bottom portion of the cavity is substantially less than a width of the particle.

29. The system of claim 1, wherein the cover layer is removable.

30. The system of claim 1, wherein a portion of the supporting member is substantially transparent to a portion of light produced by the light source.

31. The system of claim 1, further comprising a conduit coupled to the sensor array, wherein the conduit is configured to conduct the fluid sample to and away from the sensor array;

and

a vacuum chamber coupled to the conduit, wherein the vacuum chamber comprises a breakable barrier positioned between the vacuum chamber and the conduit, and wherein the vacuum chamber is configured to pull the fluid through the conduit when the breakable barrier is punctured.