Methods and apparatus for detecting cardiac injury markers using an acoustic device

• US 7,598,094 B2
• Filed: 05/02/2006
• Issued: 10/06/2009
• Est. Priority Date: 05/02/2005
• Status: Active Grant

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Miller, Michael, Masters, Brett P., Lundstrom, Mark
• Primary Examiner(s): Jung; Unsu
• Application Number:
  US11/417,005
• Publication Number:
  US 20060257945A1
• Time in Patent Office: 1,253 Days
• Field of Search: 435/7.1, 435/7.94, 436/526, 422/68.1, 422/81, 422/82.13, 422/100, 422/104
• 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 2291/02836 Flow rate, liquid level
• CPC Class Codes: G01N 2291/0422 Shear waves, transverse waves, horizontally polarised waves
• 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 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 33/56911 Bacteria
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods for detecting cardiac injury by detecting one or more cardiac markers are provided. A plurality of particles, each of which is coated with a capture agent having an affinity for a cardiac marker, 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 optionally 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 one or more cardiac markers in a sample, the method comprising the steps of:

a) introducing a fluid comprising a sample and a plurality of magnetic particles coated with a first capture agent capable of binding a cardiac marker into a fluid chamber, wherein at least one surface of the fluid chamber comprises a flexural plate wave device having a second capture agent capable of binding the cardiac marker, 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 at a surface of the membrane to attract magnetic particles in the fluid toward the membrane;

c) monitoring a first signal output by said 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 one or more cardiac markers in the sample.

2. The method of claim 1, wherein an increased level of said cardiac marker is detected compared to a reference, which is indicative of cardiac injury.

3. The method of claim 1, wherein prior to being introduced into the fluid chamber, said plurality of particles has been exposed to the sample.

4. The method of claim 1, wherein the sample has been introduced into the fluid chamber prior to introducing the plurality of particles.

5. The method of claim 1, wherein the sample is selected from the group consisting of blood, plasma, serum, cerebrospinal fluid, urine, saliva, and biopsy material.

6. The method of claim 1, wherein the one or more cardiac markers is selected from the group consisting of c-troponin-I, creatine kinase MB (CK-MB), and ischemia modified albumin.

7. The method of claim 1, wherein said cardiac marker is c-troponin-I.

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

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

10. The method of claim 1, wherein said second capture agent capable of binding the cardiac marker is indirectly bound to said surface.

11. The method of claim 10, wherein said surface is coated with a first member of a binding pair, and said second capture agent is bound to a second member of the binding pair.

12. The method of claim 11, wherein a first member of the binding pair is biotin.

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

14. The method of claim 13, wherein the first capture agent and the second capture agent are the same capture agent.

15. The method of claim 11, wherein a second member of the binding pair is a derivative of avidin.

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