Multi-shell microspheres with integrated chomatographic and detection layers for use in array sensors

• US 20060228256A1
• Filed: 02/09/2004
• Published: 10/12/2006
• Est. Priority Date: 02/07/2003
• Status: Abandoned Application

• 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: Goodey, Adrain, Shear, Jason, Neikirk, Dean P., McDevitt, John T., Anslyn, Eric
• Application Number:
  US10/544,954
• Publication Number:
  US 20060228256A1
• Time in Patent Office: Days
• US Class Current: 422/82.50
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• 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: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 15/1433 : using image recognition
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• 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 33/5432 : Liposomes or microcapsules
• CPC Class Codes: G01N 33/545 : Synthetic resin

Abstract

The development of miniaturized chromatographic systems localized within individual polymer microspheres and their incorporation into a bead-based cross-reactive sensor array platform is described herein. The integrated chromatographic and detection concept is based on the creation of distinct functional layers within the microspheres. In this first example of the new methodology, complexing ligands have been selectively immobilized to create “separation” layers harboring an affinity for various analytes. Information concerning the identities and concentrations of analytes may be drawn from the temporal properties of the beads'"'"' optical responses. Varying the nature of the ligand in the separation shell yields a collection of cross-reactive sensing elements well suited for use in array-based micro-total-analysis systems.

Claims

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

a light source;

a sensor array, the sensor array comprising a supporting member comprising at least one cavity formed within the supporting member;

at least one particle, wherein the particle is positioned within at least one cavity, and wherein the particle comprises an indicator coupled to a polymeric resin, and wherein the indicator is disposed in a core region of the polymeric resin, and wherein the indicator is substantially absent from an exterior region of the polymeric resin; and

a detector, the detector being configured to detect the interaction of the analyte with at least one 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.

4. The system of claim 1, wherein the sensor array further comprises a top cover layer, wherein the top cover layer is coupled to a top surface of the supporting member;

and wherein the top cover layer is coupled to the supporting member such that the particle is substantially contained within the cavity by the top cover layer.

11. The system of claim 1, wherein the particles produce a detectable pattern in the presence of the analyte.

12. The system of claim 1, wherein the cavity is configured such that the fluid entering the cavity passes through the supporting member during use.

17. The system of claim 1, further comprising channels in the supporting member, wherein the channels are configured to allow the fluid to flow through the channels into and away from the cavity.

20. The system of claim 1, wherein the particle further comprises a receptor coupled to the polymeric resin, wherein the receptor is disposed in the exterior region of the polymeric resin.

21. The system of claim 20, wherein the receptor is configured to alter a diffusion rate of the analyte through the polymeric resin.

22. The system of claim 1, wherein the polymeric resin comprises a polystyrene-polyethylene glycol copolymer.

2-3. -3. (canceled)

5-10. -10. (canceled)

13-16. -16. (canceled)

18-19. -19. (canceled)

23. A method of sensing an analyte in a fluid comprising:

passing a fluid over a sensor array, the sensor array comprising at least one particle positioned within at least one cavity of a supporting member, wherein the particle comprises an indicator coupled to a polymeric resin, and wherein the indicator is disposed in a core region of the polymeric resin, and wherein the indicator is substantially absent from an exterior region of the polymeric resin;

monitoring a spectroscopic change of the particle as the fluid is passed over the sensor array, wherein the spectroscopic change is caused by the interaction of the analyte with the particle.

24. The method of claim 23, wherein monitoring the spectroscopic change of the particle comprises monitoring the spectroscopic change over a predetermined period of time.

32. The method of claim 23, further comprising simultaneously determining the presence of two or more analytes in a fluid sample.

25-31. -31. (canceled)

33-38. -38. (canceled)

39. A sensor array for detecting an analyte in a fluid comprising:

a supporting member comprising a plurality of cavities formed within the supporting member;

a plurality of particles, wherein the particles are positioned within at least one cavity, and wherein the particles comprise an indicator coupled to a polymeric resin, and wherein the indicator is disposed in a core region of the polymeric resin, and wherein the indicator is substantially absent from an exterior region of the polymeric resin.

40. The system of claim 39, wherein the sensor array further comprises a top cover layer, wherein the top cover layer is coupled to a top surface of the supporting member;

and wherein the top cover layer is coupled to the supporting member such that the particle is substantially contained within the cavity by the top cover layer.

43. The system of claim 39, further comprising a fluid delivery system coupled to the supporting member.

44. The system of claim 39, wherein the particles produce a detectable pattern in the presence of the analyte.

45. The system of claim 39, wherein the cavity is configured such that the fluid entering the cavity passes through the supporting member during use.

49. The system of claim 39, further comprising channels in the supporting member, wherein the channels are configured to allow the fluid to flow through the channels into and away from the cavity.

52. The system of claim 39, wherein the particle further comprises a receptor coupled to the polymeric resin, wherein the receptor is disposed in the exterior region of the polymeric resin.

53. The system of claim 39, wherein the receptor is configured to alter a diffusion rate of the analyte through the polymeric resin.

54. The system of claim 39, wherein the polymeric resin comprises a polystyrene-polyethylene glycol copolymer.

41-42. -42. (canceled)

46-48. -48. (canceled)

50-51. -51. (canceled)