Method of preparing a sensor array

• US 6,649,403 B1
• Filed: 01/31/2001
• Issued: 11/18/2003
• 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): Ponnaluri, Padmashri
• Assistant Examiner(s): TRAN, MY CHAU T
• Application Number:
  US09/775,353
• Time in Patent Office: 1,021 Days
• Field of Search: 422/68.1, 422/67, 422/82.07, 422/55, 422/58, 435/6, 435/7.1, 435/286.1, 435/287.1, 435/288.2, 435/288.4, 435/288.5, 435/287.3, 436/518, 436/524, 436/531
• US Class Current: 435/288.5
• 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 method for forming a sensor array configured to detect an analyte in a fluid, comprising:

forming a cavity in a supporting member;

placing a particle in the cavity, wherein the particle is configured to produce a signal when the particle interacts with the analyte, and wherein the particle is placed in the cavity using an automated particle dispensing machine; and

positioning a cover over the supporting member, wherein the cover is positioned at a fixed distance over the cavity such that a channel is formed between the supporting member and the cover to allow the fluid to enter the cavity via the formed channel wherein the fixed distance is such that the cover inhibits dislodgment of the particle from the cavity during use.

2. The method of claim 1, wherein forming the cavity comprises anisotropically etching a silicon wafer.

3. The method of claim 1, wherein forming the cavity comprises anisotropically etching a silicon wafer such that sidewalls of the cavity are tapered at an angle from about 50 degrees to about 60 degrees.

4. The method of claim 1, wherein the automated particle dispensing machine comprises a vacuum dispenser head.

5. The method of claim 1, wherein the automated particle dispensing machine comprises a vacuum dispenser head, and wherein placing a particle in the cavity comprises:

placing the vacuum dispenser head over the particle;

applying vacuum to the vacuum dispenser head, wherein the applied vacuum causes the particle to become removably attached to the dispenser head;

moving the dispenser head to a position proximate to the cavity; and

removing the vacuum, wherein the removal of the vacuum causes the particle to drop into the cavity.

6. The method of claim 1, wherein the automated particle dispensing machine comprises a solid dispenser head.

7. The method of claim 1, wherein the automated particle dispensing machine comprises a solid dispenser head, and wherein placing a particle in the cavity comprises:

placing the solid dispenser head over the particle, wherein the electrostatic interaction between the particle and the dispenser head causes the particle to become removably attached to the dispenser head; and

moving the dispenser head to a position proximate to the cavity, wherein the electrostatic interaction between the particle and the cavity causes the particle to fall into the cavity.

8. The method of claim 1, wherein the automated particle dispensing machine comprises a pipette type dispenser head.

9. The method of claim 1, wherein the automated particle dispensing machine comprises a pipette type dispenser head, and wherein placing a particle in the cavity comprises:

placing the particle in a compartment of the pipette type dispenser head,

suspending the particle in a liquid;

moving the dispenser head to a position proximate to the cavity; and

forcing a portion of the liquid out of the dispenser head, wherein forcing liquid out of the dispenser head causes the particle to drop into the cavity.

10. The method of claim 1, wherein the cover comprises a developed layer of a dry photoresist film.

11. The method of claim 1, wherein the cover comprises plastic, glass, quartz, silicon nitride, or silicon oxide.

12. The method of claim 1, wherein the formed cavity is configured to allow the fluid to pass through the supporting member.

13. The method of claim 1, further comprising forming channels in the supporting member wherein the channels are configured to allow the fluid to pass through the supporting member to and from the cavity.

14. The method of claim 1, further comprising forming a pump on the supporting member, the pump being configured to pump the fluid to the cavity.

15. The method of claim 1, wherein the supporting member comprises a plastic material.

16. The method of claim 1, wherein the supporting member comprises a plastic material, and wherein the cavity is formed by drilling the supporting member.

17. The method of claim 1, wherein the supporting member comprises a plastic material, and wherein the cavity is formed by transfer molding the supporting member.

18. The method of claim 1, wherein the supporting member comprises a plastic material, and wherein the cavity is formed by a punching device.

19. The method of claim 1, wherein the size of the particle ranges from about 0.05 micron to about 500 microns.

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

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

22. The method 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.

23. The method 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.

24. The method 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.

25. The method of claim 1, further comprising coating an inner surface of the cavity with a material to increase adhesion of the particle to the inner surface of the cavity.

26. The method of claim 1, further comprising coating an inner surface of the cavity with a material to increase reflectivity of the inner surface of the cavity.

27. The method of claim 1, further comprising forming an optical detector upon a bottom surface of the supporting member below the cavity.

28. The method of claim 1, wherein the fixed distance over the cavity is substantially less than a width of the particle.