Method and system for the detection of cardiac risk factors

• US 8,257,967 B2
• Filed: 04/28/2003
• Issued: 09/04/2012
• Est. Priority Date: 04/26/2002
• Status: Active Grant

• Current Assignee: National Institutes of Health (NIH) (Government of the United States of America)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: McDevitt, John T., Anslyn, Eric V., Shear, Jason B., Neikirk, Dean P., Christodoulides, Nick J.
• Primary Examiner(s): Yang, N. C.
• Application Number:
  US10/427,744
• Publication Number:
  US 20040029259A1
• Time in Patent Office: 3,417 Days
• Field of Search: 422/68.1, 422 81- 8209, 435286-2871, 4352884-2887, 436/518, 436/524, 436/531
• US Class Current: 435/288.7
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00416 Vacuum
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00468 by manipulation of individual beads
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00578 electrophoric
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• 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 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2001/021 : Correlating sampling sites with geographical information, e.g. GPS
• 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 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 2800/32 : Cardiovascular disorders
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54373 : involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/6893 : related to diseases not provided for elsewhere
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/028 : having reaction cells in the form of microtitration plates

Abstract

A system for the rapid characterization of multi-cardiovascular risk factor analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member, in which a plurality of cavities may be formed. A series of chemically sensitive particles, in one embodiment, are positioned within the cavities. The particles may produce a signal when a receptor, coupled to the particle, interacts with the cardiovascular risk factor analyte and the particle-analyte complex is visualized using a visualization reagent. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized. In an embodiment, each cavity of the plurality of cavities is designed to capture and contain a specific size particle. Flexible projections may be positioned over each of the cavities to provide retention of the particles in the cavities.

Claims

1. A system for detecting cardiovascular risk factor analytes in a fluid, comprising:

a light source;

a sensor array, the sensor array comprising a supporting member comprising a plurality of cavities formed within the supporting member;

a plurality of particles, wherein an individual particle is positioned within an individual cavity and is configured to produce a signal in the presence of a cardiovascular risk factor, wherein the cardiovascular risk factor comprises C-reactive protein, high density lipoprotein, low density lipoprotein, very low density lipoprotein, cholesterol, interleukin-6, intercellular adhesion molecule-1, fibrinogen, homocysteine, folate, calcium, lipoprotein a, apolipoprotein A-1, apolipoprotein B, Helicobacter pylori, chlamydia pneumoniae, Herpes virus hominis, and cytomegalovirus; and

a detector, wherein the detector is configured to detect the signal produced by the particles during use.

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

3. The system of claim 1, wherein the light source comprises a white light source.

4. The system of claim 1, wherein the light source comprises a red light emitting diode, a blue light emitting diode, and a green light emitting diode.

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

and wherein both the bottom layer and the cover are coupled to the supporting member such that at least one of the particles is substantially contained within at least one of the cavities by the bottom layer and the cover, and wherein the bottom layer and the cover are substantially transparent to light produced by the light source.

6. The system of claim 1, wherein the sensor array further comprises a bottom layer coupled to the supporting member, and wherein the supporting member comprises silicon, and wherein the bottom layer comprises silicon nitride.

7. The system of claim 1, wherein the sensor array further comprises a cover, the cover being coupled to the supporting member such that at least one of the particles is substantially contained within at least one of the cavities by the cover, and wherein the cover is configured to allow the fluid to pass through the cover to at least one of the particles, and wherein both the supporting member and the cover are substantially transparent to light produced by the light source.

8. The system of claim 1, wherein the sensor array further comprises a cover positioned at a distance above the upper surface of the supporting member such that an opening is formed between the supporting member and the cover to allow the fluid to enter at least one of the cavities via the opening, and wherein the cover inhibits dislodgment of at least one of the particles from at least one of the cavities during use.

9. The system of claim 1, wherein at least one of the cavities is configured such that the fluid entering the cavity passes through the supporting member during use.

10. The system of claim 1, wherein at least one of the cavities is substantially tapered such that the width of the tapered 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 tapered cavity is substantially less than a width of at least one of the particles.

11. The system of claim 1, wherein an inner surface of one or more of the cavities is coated with a reflective material.

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

13. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin.

14. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein the polymeric resin comprises polystyrene-polyethylene glycol-divinyl benzene.

15. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein at least one of the particles further comprises a first indicator and a second indicator, the first and second indicators being coupled to the receptor molecule, wherein the interaction of the receptor molecule with at least one of the cardiac risk factor analytes causes the first and second indicators to interact such that the signal is produced.

16. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein at least one of the particles further comprises an indicator, wherein the indicator is associated with the receptor molecule such that in the presence of at least one of the cardiac risk factor analytes the indicator is displaced from the receptor molecule to produce the signal.

17. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein the receptor molecule comprises a peptide.

18. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein the receptor molecule comprises an enzyme.

19. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein the receptor molecule comprises a synthetic receptor.

20. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein the receptor molecule comprises an antibody.

21. The system of claim 1, wherein at least one of the particles comprises a receptor molecule coupled to a polymeric resin, and wherein the receptor molecule comprises an antigen.

22. The system of claim 1, wherein the supporting member comprises silicon.

23. The system of claim 1, wherein the supporting member comprises a plastic material.

24. The system of claim 1, wherein the supporting member comprises a dry film photoresist material.

25. The system of claim 1, wherein the supporting member comprises a plurality of layers of a dry film photoresist material.

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

27. The system of claim 1, wherein the sensor array further comprises a pump coupled to the supporting member, wherein the pump is configured to direct the fluid towards at least one of the cavities, and wherein a channel is formed in the supporting member, the channel coupling the pump to the cavity such that the fluid flows through the channel to at least one of the cavities during use.

28. 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 is configured to pull the fluid through the conduit when the vacuum chamber is activated.

29. 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 filter coupled to the conduit and the sensor array, wherein the fluid passes through the filter before reaching the sensor array.

30. A system for detecting cardiovascular risk factor analytes in a fluid comprising:

a light source;

a sensor array, the sensor array comprising a supporting member comprising a plurality of cavities formed within the supporting member;

a plurality of particles, wherein an individual particle is positioned within an individual cavity, wherein a particle is configured to produce a signal when the particle interacts with a cardiovascular risk factor analyte during use, the cardiovascular risk factor comprising C-reactive protein, interleukin-6, and one or more of high density lipoprotein, low density lipoprotein, very low density lipoprotein, cholesterol, intercellular adhesion molecule-1, fibrinogen, homocysteine, folate, calcium, lipoprotein a, apolipoprotein A -1, apolipoprotein B, Helicobacter pylori, chlamydia pneumoniae, Herpes virus hominis, and cytomegalovirus; and

a detector, wherein the detector is configured to detect the signals produced by the interaction of the particles with the cardiovascular risk factor analytes during use;

wherein the system is configured to simultaneously determine the presence of the cardiovascular risk factors.