Multiple-probe diagnostic sensor

• US 5,976,466 A
• Filed: 04/15/1992
• Issued: 11/02/1999
• Est. Priority Date: 08/21/1989
• Status: Expired due to Term

• Current Assignee: Board of Regents of The University of Washington (University of Washington)
• Original Assignee: Board of Regents of The University of Washington (University of Washington)
• Inventors: Francese, James E., Ratner, Buddy D.
• Primary Examiner(s): ALEXANDER, LYLE
• Application Number:
  US07/869,899
• Time in Patent Office: 2,757 Days
• Field of Search: 436/86, 436/149, 436/151, 436/172, 422/52-53, 422/62, 422/68.1, 422/82.05, 422/82.11, 250/361 C, 250/461.1, 385/130
• US Class Current: 422/82.11
• CPC Class Codes: G01N 2291/014 Resonance or resonant frequency
• CPC Class Codes: G01N 2291/02466 Biological material, e.g. blood
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0423 Surface waves, e.g. Rayleigh waves, Love waves
• CPC Class Codes: G01N 2291/0426 Bulk waves, e.g. quartz crystal microbalance, torsional waves
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 2291/106 one or more transducer arrays
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 29/449 Statistical methods not provided for in G01N29/4409, e.g. averaging, smoothing and interpolation
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/545 Synthetic resin

Abstract

There is disclosed a diagnostic sensor device comprising a plurality of sensor probes, a detection device, and a computer for analyzing the signals generated from each sensor probe by multivariate statistical analysis. The plurality of sensor probes comprise a substrate that allows transmission of a signal and a partially selective surface coating the substrate wherein the partially selective surface binds proteins from a biological fluid by multiple, noncovalent interactions, and with the proviso that the partially selective surfaces of each sensor probe in the diagnostic sensor device be different. The diagnostic sensor device can be used as a method for diagnosing disease states in humans and animals, wherein the disease states are characterized by altered protein character and behavior of a biological fluid.

Claims

1. A diagnostic sensor device comprising:

a plurality of sensor probes in communication with at least one signal-generating device that generates a signal to the sensor probes, wherein each sensor probe comprises a substrate that allows for the transmission of the signal and a partially selective surface, wherein the partially selective surface binds proteins within a biological fluid through multiple, noncovalent and non-specific interactions, and wherein the partially selective surface of each sensor probe partitions the proteins within the biological fluid in a different manner;

a means for detecting the signals, the detection means in communication with the plurality of sensor probes and detecting the signals after signal interaction with each partially selective surface; and

a means for analyzing the signals from each partially selective surface by multivariate analysis, the analyzing means in communication with the detection means.

2. The diagnostic sensor device of claim 1 wherein the means for analyzing the signals from each partially selective surface is a computer with multivariate statistical analysis software.

3. The diagnostic sensor device of claim 1 wherein the partially selective surface is a plasma-polymerized film, a spin-coated polymer, a plasma-etched surface, or a metal-sputtered surface.

4. The diagnostic sensor device of claim 1 wherein the partially selective surface is a plasma-polymerized film of a polymerized monomer, wherein the monomer is selected from the group consisting of 2-mercaptoethanol, allylamine, allyl alcohol, acrylic acid, methane, benzene, tetrafluoroethane, methanol, acetone, chloroform, carbon tetrachloride, hexamethyldisilane, ethyl sulfide, ethyl chloroformate, 1,1,1,3,3,3,-Hexamethyldisilazane, acrylonitrile, trimethyldiborane, pyridine, tetramethylgermanium, 2-chloropropane, formic acid, ethylene oxide, ferrocene, diphenyl selenide, butanone, bromobenzene, trimethyl borate, tetrahydrofuran, chlorotrimethylsilane, hydroxyethylmethacrylate, vinyltrimethylsilane, dimethyl sulfoxide, hexafluorobenzene, perfluoropropane, allene, organometallics, and combinations thereof.

5. The diagnostic sensor of claim 1 wherein the partially selective surface is a plasma-etched surface produced by a plasma-etching gas, and wherein the plasma-etching gas is selected from the group consisting of argon, neon, nitrogen, air, helium, oxygen, fluorine, iodine, diborine, phosphine, krypton, sulfur dioxide, silicon (IV) chloride, and combinations thereof.

6. The diagnostic sensor device of claim 1 wherein the detection means is selected from the group consisting of infrared spectroscopy, UV spectroscopy, visible spectroscopy, surface acoustic wave devices, bulk acoustic wave devices, capacitance measurements, radioimmunoassay measurements, chemiluminescence measurements, Lamb-wave measurements, fluorescence measurements, Wilhelmy balance, chemiresistor measurements, electrochemical sensors, and enzyme-linked immunosorbent assay.

7. The diagnostic sensor device of claim 1 wherein at least one sensor probe further comprises a base, and wherein the substrate and the partially selective surface are the same and the substrate is supported by the base.

8. The diagnostic sensor device of claim 7 wherein the substrate and the partially selective surface are a thin film waveguide.

9. An analyte-measuring device for measuring an analyte or analytes in a biological fluid, comprising:

a plurality of sensor probes in communication with at least one signal-generating device that generates a signal to the sensor probes, wherein each sensor probe comprises a substrate that allows for the transmission of the signal and a partially selective surface, wherein the partially selective surface binds proteins within the biological fluid through multiple, noncovalent and non-specific interactions, with the proviso that the partially selective surface of each sensor probe partitions the proteins within the biological fluid in a different manner;

a means for detecting the signals, the detection means in communication with the plurality of sensor probes and detecting the signals after signal interaction with each partially selective surface; and

a means for analyzing the signals from each partially selective surface by multivariate analysis, the analyzing means in communication with the detection means.

10. The analyte-measuring device of claim 9 wherein the means for analyzing the signals from each partially selective surface is a computer with multivariate statistical analysis software.

11. The analyte-measuring device of claim 9 wherein the partially selective surface is a plasma-polymerized film, a spin-coated polymer, a plasma-etched surface, or a metal-sputtered surface.

12. The analyte-measuring device of claim 9 wherein the partially selective surface is a plasma-polymerized film of a polymerized monomer, wherein the monomer is selected from the group consisting of 2-mercaptoethanol, allylamine, allyl alcohol, acrylic acid, methane, benzene, tetrafluoroethane, methanol, acetone, chloroform, carbon tetrachloride, hexamethyldisilane, ethyl sulfide, ethyl chloroformate, 1,1,1,3,3,3,-Hexamethyldisilazane, trimethyldiborane, acrylonitrile, pyridine, tetramethylgermanium, 2-chloropropane, formic acid, ethylene oxide, ferrocene, diphenyl selenide, butanone, bromobenzene, trimethyl borate, tetrahydrofuran, chlorotrimethylsilane, hydroxyethylmethacrylate, vinyltrimethylsilane, dimethyl sulfoxide, hexafluorobenzene, perflouropropane, allene, organometallics, and combinations thereof.

13. The analyte-measuring device of claim 9 wherein the partially selective surface is a plasma-etched surface produced by a plasma-etching gas, and wherein the plasma-etching gas is selected from the group consisting of argon, neon, nitrogen, air, helium, oxygen, fluorine, iodine, diborine, phosphine, krypton, sulfur dioxide, silicon (IV) chloride, and combinations thereof.

14. The analyte-measuring device of claim 9 wherein the detection means is selected from the group consisting of infrared spectroscopy, UV spectroscopy, visible spectroscopy, surface acoustic wave devices, bulk acoustic wave devices, capacitance measurements, radioimmunoassay measurements, chemiluminescence measurements, Lamb-wave measurements, fluorescence measurements, Wilhelmy balance, chemiresistor measurements, electrochemical sensors, and enzyme-linked immunosorbent assay.

15. The analyte-measuring device of claim 9 wherein at least one sensor probe further comprises a base, and wherein the substrate and the partially selective surface are the same and the substrate is supported by the base.

16. The analyte-measuring device of claim 15 wherein the substrate and the partially selective surface are a thin film waveguide.