Method and apparatus for detection of analyte using an acoustic device

• US 7,648,844 B2
• Filed: 05/02/2006
• Issued: 01/19/2010
• Est. Priority Date: 05/02/2005
• Status: Active Grant

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Srivastava, Alok, Lundstrom, Mark, Wang, Wayne U., Miller, Michael, Masters, Brett P.
• Primary Examiner(s): Jung; Unsu
• Application Number:
  US11/416,789
• Publication Number:
  US 20090148857A1
• Time in Patent Office: 1,358 Days
• Field of Search: None
• US Class Current: 436/526
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• 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 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 29/4418 with a model, e.g. best-fit, regression analysis
• CPC Class Codes: G01N 33/54313 the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/9493 Immunosupressants

Abstract

Methods for detecting analytes in a sample are provided. A plurality of particles, each of which is coated with a capture agent having an affinity for the analyte, is combined with the sample to form a plurality of analyte-particle complexes. The system also includes a transport arrangement for transporting the sample to the sensor surface, and a magnetic field inducing structure constructed and arranged to establish a magnetic field at and adjacent to the sensor surface. The resonant sensor produces a signal corresponding to an amount of analyte-particle complexes that are bound to the sensor surface.

Claims

1. A method for detecting whether one or more analytes is present in a sample comprising:

a) introducing a fluid comprising a sample, a plurality of magnetic particles and a competitor molecule into a fluid chamber, said magnetic particles being coated with a first capture agent capable of binding the analyte, wherein at least one surface of the fluid chamber comprises a flexural plate wave device that has been coated with a second capture agent capable of binding to the competitor molecule, wherein the flexural plate wave device has a membrane that is capable of vibrating, and wherein the second capture agent is bound to the membrane;

b) applying a retractable source of magnetic flux positioned external to the fluid chamber close to the membrane to create a significant magnetic field gradient to attract at least one of the plurality of magnetic particles in the fluid toward the membrane;

c) monitoring a first signal output by the flexural plate wave device, wherein the first signal output is monitored in the presence of a magnetic flux;

d) after removing the retractable source of magnetic flux, flowing a solution through the fluid chamber to remove magnetic particles not bound to the membrane;

e) monitoring a second signal output by said flexural plate wave device, wherein the second signal output is monitored in the absence of the magnetic flux; and

f) comparing the first and the second signal output to a control signal, thereby detecting whether one or more analytes is present in the sample.

2. The method of claim 1, wherein prior to being introduced into the fluid chamber, said plurality of magnetic particles has been exposed to the sample and to the competitor molecule.

3. The method of claim 1, wherein the competitor molecule comprises the immunosuppressant bound to a tag and the second capture agent is capable of binding to the tag.

4. The method of claim 3, wherein the tag is biotin.

5. The method of claim 1, wherein the competitor molecule comprises two or more analyte molecules bound to a carrier, and the second capture agent is capable of binding the analyte.

6. The method of claim 5, wherein the carrier is a selected from the group consisting of horseradish peroxidase and albumin.

7. The method of claim 1, wherein the sample and the competitor molecule have been introduced into the fluid chamber prior to introducing the plurality of magnetic particles.

8. The method of claim 1, wherein the sample is a biological sample.

9. The method of claim 8, wherein the biological sample is selected from the group consisting of:

saliva, sputum, cerebrospinal fluid, blood, serum, plasma, urine, and biopsy material.

10. The method of claim 1, wherein the control signal is a standard curve.

11. The method of claim 1, wherein the control signal is obtained without the sample.

12. The method of claim 1, wherein the second capture agent is indirectly bound to said surface.

13. The method of claim 12, wherein said surface is coated with a first member of a binding pair, and the second capture agent is bound to a second member of the binding pair.

14. The method of claim 13, wherein the first member of the binding pair is biotin.

15. The method of claim 1, wherein the first or second capture agent is an antibody.

16. The method of claim 13, wherein the second member of the binding pair is a derivative of avidin.

17. The method of claim 1, wherein a fluid flows across the membrane during one or more of steps of a), b), c) and e).