Method and Apparatus for Analyzing Bioprocess Fluids

• US 20100233031A1
• Filed: 05/25/2010
• Published: 09/16/2010
• Est. Priority Date: 05/02/2005
• Status: Abandoned Application

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Masters, Brett P.
• Application Number:
  US12/787,084
• Publication Number:
  US 20100233031A1
• Time in Patent Office: Days
• US Class Current: 422/69
• 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 25/00 Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
• 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 33/54326 Magnetic particles
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/9493 Immunosupressants
• 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: G01R 33/093 : using multilayer structures, e.g. giant magnetoresistance sensors thin magnetic films H01F10/00
• CPC Class Codes: G01R 33/12 : Measuring magnetic properties of articles or specimens of solids or fluids involving magnetic resonance G01R33/20
• CPC Class Codes: G01R 33/1269 : of molecules labeled with magnetic beads magnetic particles for bio assay G01N33/54326

Abstract

Methods and apparatus for analyzing bioprocess fluids are provided. A plurality of particles coated with a plurality of capture agents having an affinity for one or more biological markers is combined with bioprocess fluid to form a plurality of analyte-particle complexes. The system also includes a transport arrangement for transporting the sample to a 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. An apparatus for detecting a substance in a fluid, comprising:

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

b) a sensor device defining at least a portion of at least one interior surface of the fluid chamber and capable of being coated with a plurality of first capture agents capable of binding one or more substances in the fluid, the sensor device defining an acoustic interaction region of less than about 30 microns that acoustically interacts with the fluid in the fluid chamber;

c) a monitoring device to monitor at least one signal output by the sensor device; and

d) a plurality of particles capable of being coated with a plurality of second capture agents capable of binding the one or more substances in the fluid, wherein at least some of the plurality of particles are capable of binding to a surface of the sensor device within the acoustic interaction region.

2. The apparatus of claim 1, wherein the acoustic interaction region comprises a portion of the sensor device and particles bound at the surface of the sensor device.

3. The apparatus of claim 1, wherein the sensor device is a flexural plate wave device.

4. The apparatus of claim 1, wherein at least some of the plurality of particles bind to the surface of the sensor device within the acoustic interaction region.

5. The apparatus of claim 1, wherein binding of the at least some of the plurality of particles at the surface of the sensor device alters the at least one signal output by the sensor device.

6. The apparatus of claim 1, wherein the plurality of particles are magnetic particles.

7. The apparatus of claim 6 further comprising a retractable source of magnetic flux positioned external to the fluid chamber close to the at least one interior surface of the fluid chamber to create a magnetic field gradient to selectively direct magnetic particles toward the surface of the sensor device.

8. The apparatus of claim 1, wherein the at least one interior surface of the fluid chamber further comprises a plurality of first capture agents bound to the surface of the sensor device, wherein the plurality of first capture agents are capable of binding the one or more substances.

9. The apparatus of claim 1, wherein the plurality of particles further comprises a plurality of second capture agents bound to the plurality of particles, wherein the plurality of second capture agents are capable of binding the one or more substances.

10. The apparatus of claim 1, wherein the plurality of first capture agents are indirectly bound to the surface of the sensor device.

11. The apparatus of claim 1, wherein the plurality of first capture agents are directly bound to the surface of the sensor device.

12. The apparatus of claim 1, wherein the plurality of first or second capture agents comprise a plurality of polypeptides.

13. The apparatus of claim 1, wherein the plurality of first or second capture agents comprise an antibody.

14. The apparatus of claim 1, wherein the one or more substances comprise an analyte.

15. The apparatus of claim 1, wherein the one or more substances comprise a tag.

16. The apparatus of claim 15, wherein the tag is bound by an analyte.

17. The apparatus of claim 15, wherein the tag is linked to an analyte.

18. The apparatus of claim 1, wherein the one or more substances comprise a binding partner for an analyte.

19. The apparatus of claim 1, wherein the monitoring device monitors at a plurality of points in time.

20. The apparatus of claim 1, wherein the monitoring device monitors a change in the at least one signal output.

21. The apparatus of claim 1 further comprising a fluid control device for flowing one or more fluids over the surface of the sensor device.

22. The apparatus of claim 21 wherein the one or more fluids comprise a wash flow to remove particles not bound at the surface of the sensor device.

23. The apparatus of claim 1, wherein the acoustic interaction region is between about 10 microns and about 30 microns.

24. The apparatus of claim 1, wherein the acoustic interaction region is less than about 10 microns.