Method and apparatus for detection of analyte using a flexural plate wave device and magnetic particles

• US 7,300,631 B2
• Filed: 07/18/2005
• Issued: 11/27/2007
• Est. Priority Date: 05/02/2005
• Status: Active Grant

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Miller, Michael F., Masters, Brett P., Lundstrom, Mark E.
• Primary Examiner(s): Le; Long V.
• Assistant Examiner(s): Jung; Unsu
• Application Number:
  US11/183,484
• Publication Number:
  US 20060286685A1
• Time in Patent Office: 862 Days
• Field of Search: 435/7.1, 435/287.3, 435/287.9, 435/288.4, 435/288.5, 436/526, 422/68.1, 422/81, 422101-404, 73/240.6
• US Class Current: 422/82.01
• 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

A system for detecting an analyte in a sample includes a resonant sensor that has a sensor surface coated with the capture agent. A plurality of magnetic 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. An apparatus for detection of an analyte, the apparatus comprising:

a fluid chamber having at least one opening for fluid to enter;

a flexural plate wave device defining at least a portion of at least one interior surface of the fluid chamber and having a vibrating membrane;

a monitoring device to monitor at least one signal representative of the propagation characteristics of the vibrating membrane output by the flexural plate wave device;

a plurality of magnetic particles coated with a capture agent having an affinity for the analyte; and

a retractable source of magnetic flux positioned external to the fluid chamber close to the vibrating member to create significant magnetic field gradients at the surface of the vibrating member to selectively attract the magnetic particles in the fluid to the at least one interior surface of the fluid chamber, the source of magnetic flux being retractable away from the fluid chamber.

2. The apparatus of claim 1, further comprising a fluid control device adapted to change at least one of fluid flow, pressure or trajectory in the fluid chamber.

3. The apparatus of claim 1 wherein the source of magnetic flux is capable of being located external to the fluid chamber within 200 μ

m of the interior surface of the at least one interior surface of the fluid chamber.

4. The apparatus of claim 1, further comprising a second source of magnetic flux.

5. The apparatus of claim 1, further comprising a characterizing device to characterize a property of the magnetic particles attracted to the at least one interior surface.

6. The apparatus of claim 5 wherein the property is selected from the group consisting of particle concentration, density, size and combinations thereof.

7. The apparatus of claim 1, further comprising an identification device to track use of the apparatus.

8. The apparatus of claim 1, further comprising a flow diverter to alter fluid flow in the fluid chamber.

9. The apparatus of claim 1, wherein the flexural plate wave device comprises a plurality of interdigitated electrodes.

10. The apparatus of claim 1, further comprising a filter wherein the fluid passes through the filter prior to entering the fluid chamber.

11. The apparatus of claim 1, wherein the source of magnetic flux is retracted away from the fluid chamber to substantially reduce magnetic fields in the vicinity of the at least one surface of the fluid chamber.

12. The apparatus of claim 11, wherein the monitoring device monitors the at least one signal output by the flexural plate wave device while the fluid is flowing through the apparatus.

13. The apparatus of claim 12, wherein the flow rate of the fluid is increased.

14. The apparatus of claim 1, wherein the source of magnetic flux is positioned within 100 μ

m of the interior surface of the fluid chamber.

15. A cartridge for a resonant device system, the cartridge comprising:

a first fluid chamber having at least one opening for fluid to enter;

a flexural plate wave device defining at least one interior surface of the fluid chamber and having a vibrating membrane; and

a retractable source of magnetic flux positioned external to the fluid chamber close to the vibrating membrane to create significant magnetic field gradients at the surface of the vibrating membrane to selectively attract magnetic particles to the at least one interior surface of the first fluid chamber, the source of magnetic flux being retractable away from the fluid chamber.

16. The cartridge of claim 15, further comprising a second fluid chamber comprising at least one outlet in fluid communication with the at least one opening of the first fluid chamber.

17. The cartridge of claim 16, wherein the plurality of magnetic particles are initially disposed within the second fluid chamber.

18. The cartridge of claim 17, further comprising a second device to combine at least some of the plurality of magnetic particles with an analyte located within a fluid.

19. The cartridge of claim 15, further comprising a second source of magnetic flux.

20. The cartridge of claim 15, further comprising a characterizing device to characterize a property of the magnetic particles attracted to the at least one interior surface.

21. The cartridge of claim 15, further comprising an identification device to track use of the cartridge.

22. The cartridge of claim 15, further comprising a flow diverter to alter fluid flow in first fluid chamber.

23. The cartridge of claim 15 wherein the source of magnetic flux is capable of being located external to the first fluid chamber within 200 μ

m of the at least one interior surface of the first fluid chamber.

24. The cartridge of claim 15, further comprising a filter wherein the fluid passes through the filter prior to entering the first fluid chamber.

25. The cartridge of claim 17, wherein the second fluid chamber comprises at least one inlet in fluid communication with an outlet of the first fluid chamber.

26. The apparatus of claim 15, wherein the source of magnetic flux is positioned within 100 μ

m of the interior surface of the fluid chamber.