Method and Apparatus for Analyzing Bioprocess Fluids

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.

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.