Method and apparatus for analyzing bioprocess fluids

• US 20070224700A1
• Filed: 12/19/2006
• Published: 09/27/2007
• Est. Priority Date: 05/02/2005
• Status: Active Grant

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Masters, Brett
• Granted Patent: US 7,749,445 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• 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. A method for analyzing a bioprocess fluid, the method comprising the steps of:

a) introducing a bioprocess fluid and a plurality of particles coated with a plurality of capture agents capable of binding one or more biological markers into a fluid chamber, wherein at least one surface of the fluid chamber comprises an acoustic device having a plurality of capture agents capable of binding the one or more biological markers bound thereto; and

b) monitoring signal output by said acoustic device, thereby detecting one or more biological markers in the bioprocess fluid.

2. The method of claim 1, wherein the bioprocess fluid is conditioned medium produced by a recombinant host cell.

3. The method of claim 2, wherein the recombinant host cell is selected from the group consisting of bacteria, fungi, insect cells, and mammalian cells.

4. The method of claim 1, wherein the bioprocess fluid comprises one or more liquids selected from the group consisting of milk, conditioned cell culture media, blood, serum, plasma, and plasma fractions.

5. The method of claim 1, wherein the bioprocess fluid comprises one or more liquids selected from the group consisting of cell homogenates and tissue homogenates.

6. The method of claim 1, wherein prior to step a), the bioprocess fluid has been subjected to one or more treatments selected from the group consisting of removal of particulate matter, diafiltration, size fractionation, chromatography, and dilution.

7. The method of claim 1, wherein the one more biological markers comprises host cell protein.

8. The method of claim 1, wherein the one more biological markers comprises one or more contaminants.

9. The method of claim 8, wherein the one or more contaminants are bacterial antigens.

10. The method of claim 8, wherein the contaminants is a virus.

11. The method of claim 1, wherein the one or more biological markers are selected from the group consisting of milk antigens, serum antigens, plasma antigens, and immunoglobulin aggregates.

12. The method of claim 1, wherein the acoustic device is a flexural plate wave device.

13. The method of claim 1, wherein the particles are magnetic and fuirther comprising creating a magnetic flux in proximity to the acoustic device to attract at least one of the plurality of magnetic particles toward the at least one surface.

14. The method of claim 13, wherein the magnetic flux is removed prior to step b).

15. The method of claim 1, wherein the plurality of capture agents comprises polyclonal antibody.

16. The method of claim 1, wherein the plurality of capture agents comprises a combination of two or more monoclonal antibodies.

17. A method for assessing purity of a bioprocess fluid, comprising detecting a level of one or more biological markers in the bioprocess fluid comprising:

a) introducing the bioprocess fluid and a plurality of particles coated with a plurality of capture agents capable of binding the biological marker into a fluid chamber, wherein at least one surface of the fluid chamber comprises an acoustic device having a plurality of capture agent capable of binding the one or more biological markers bound thereto; and

b) monitoring signal output by said acoustic device, thereby detecting the level of one or more biological markers in the sample, thereby assessing purity of a bioprocess fluid.

18. A method for assessing purity of a bioprocess fluid, comprising detecting a level of one or more biological markers in the bioprocess fluid comprising:

a) combining the bioprocess fluid with a plurality of magnetic particles that comprise a plurality of capture agents having an affinity for one or more biological markers to produce at least some magnetic particles bound to at least some of the one or more biological markers;

b) directing the combined fluid into a fluid chamber, wherein at least one surface of the fluid chamber comprises an acoustic device having a plurality of capture agents capable of binding the one or more biological markers bound thereto;

c) creating a magnetic flux in proximity to the flexural plate wave device to magnetically attract at least some of the plurality of bound magnetic particles to the at least one surface of the flexural plate wave device, and

d) monitoring signal output by said acoustic device, thereby detecting the level of one or more biological markers in the sample, thereby assessing purity of a bioprocess fluid.

19. The method of claim 18, further comprising selectively altering at least one of the magnetic flux in proximity to the at least one surface of the flexural plate wave device or altering at least one property of fluid flow in proximity to the at least one surface of the flexural plate wave device to selectively locate at least some of the plurality of bound magnetic particles on at least a portion of the at least one surface of the flexural plate wave device.

20. The method of claim 19 wherein the at least one property of the fluid flow is selected from the group consisting of fluid pressure, flow rate, and fluid trajectory.

21. The method of claim 19 wherein altering the at least one property of fluid flow comprises altering a flow path of the fluid to control the movement of the magnetic particles in vicinity to the at least one surface of the flexural plate wave device.

22. The method of claim 18, further comprising exciting the flexural plate wave device to selectively dislodge materials adhering to the at least one surface of the flexural plate wave device.

23. An apparatus for assessing purity of a bioprocess fluid, comprising:

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

b) a flexural plate wave 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 capture agents capable of binding one or more biological markers;

c) a monitoring device to monitor at least one signal output by the flexural plate wave device;

d) a plurality of magnetic particles capable of being coated with a plurality of capture agents capable of binding one or more biological markers; and

e) a first source of magnetic flux to selectively attract magnetic particles to the flexural plate wave device.

24. The apparatus of claim 23, wherein the at least one interior surface of the fluid chamber further comprises a plurality of capture agents capable of binding the one or more biological markers bound thereto.

25. The apparatus of claim 23, wherein the plurality of magnetic particles further comprises a plurality of capture agents capable of binding one or more biological markers bound thereto.