Apparatus and method for immunomagnetic cell separation

Abstract

An apparatus and methods are provided for the magnetic separation of target bioentities. The apparatus include a fluid chamber and a magnetic element for drawing target bioentities toward a collection surface of the fluid chamber. The apparatus may include a positioning assembly operable to variable change the position and orientation of the fluid chamber relative to the magnetic element.

1 . A system for magnetic separation of a target bioentity from a fluid suspension of target bioentities and bystander bioentities, comprising:
 a separation chamber having an opening through which the chamber can be filled with a cell suspension having magnetized or magnetizable target bioentities, wherein the separation chamber is a fluid chamber having a collection surface;   a magnetic element adjacent the separation chamber wherein the magnetic element applies a magnetic field to the separation chamber to attract the target bioentities to the collection surface;   a chamber control assembly connected with the separation chamber, wherein the chamber control assembly comprises a pivot axis for pivoting the separation chamber.   
     
     
         2 . The system of  claim 1  wherein the magnetic element is disposed at an angle relative to the horizon. 
     
     
         3 . The system of  claim 2  wherein the control assembly is operable to pivot the separation chamber into an orientation corresponding to the angle at which the magnetic element is disposed. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . The system of  claim 1  wherein chamber control assembly is operable to control the linear displacement of the separation chamber to move the separation chamber toward and away from the magnetic element. 
     
     
         7 . The system of  claim 6  wherein the chamber control assembly comprises an elongated linear guide for guide displacement of the separation chamber along a horizontal path. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The system of  claim 1  comprising a plurality of fluid reservoirs in fluid communication with the separation chamber. 
     
     
         11 . The system of  claim 10  comprising a fluid controller for controlling which of the plurality of reservoirs is in fluid communication so that only a single reservoir is in fluid communication with the separation chamber at any time. 
     
     
         12 . (canceled) 
     
     
         13 . The system of  claim 1  wherein the collection surface is configured similarly to a surface of the magnetic element. 
     
     
         14 - 17 . (canceled) 
     
     
         18 . The system of  claim 1  wherein the magnetic element applies a magnetic field through the thickness of the separation chamber. 
     
     
         19 . A method for performing magnetic separation of a bioentity, comprising the steps of:
 providing a fluid suspension in a fluid chamber wherein the fluid suspension comprises a fluid, magnetically labeled bioentities and bystander bioentities;   applying a magnetic field to the fluid chamber containing magnetically labeled bioentities in a medium such that the magnetically labeled bioentities are drawn to the collection surface.   
     
     
         20 . The method of  claim 19  including the step of positioning the fluid chamber at an angle relative to the horizon. 
     
     
         21 . The method of  claim 19  wherein the step of applying a magnetic field comprises drawing the magnetically labeled bioentities to the collection surface against gravity. 
     
     
         22 . The method of  claim 19  including step of performing a secondary separation process, comprising the steps of:
 draining the fluid and bystander bioentities from the fluid chamber while the magnetic element retains target bioentities on the collection surface; 
 introducing fluid medium into the container after the step of draining and while the magnetic element retains the target bioentities on the collection surface. 
 
     
     
         23 . The method of  claim 22  comprising the steps of:
 discontinuing the step of applying a magnetic field to the fluid chamber so that the target bioentities are no longer retained on the collection surface by the magnetic field, wherein the step of discontinuing the step of applying a magnetic field occurs after the step of introducing fluid medium into the container. 
 
     
     
         24 . The method of  claim 23  comprising the step of draining the fluid from the separation chamber after the step of discontinuing the step of applying a magnetic field. 
     
     
         25 . The method of  claim 19  comprising the step of pivoting the fluid chamber so that a meniscus of the fluid passes over an area of the collection surface to agitate bystander bioentities held adjacent the collection surface. 
     
     
         26 . The method of  claim 25  wherein the step of pivoting the chamber comprises operating a rotary actuator to pivot the fluid chamber about an axis. 
     
     
         27 . The method of  claim 23  wherein the step of discontinuing the step of applying a magnetic field comprises displacing the fluid chamber relative to a magnetic element. 
     
     
         28 . The method of  claim 27  wherein the step of displacing the fluid chamber operates to separate the collection surface from the magnetic field of the magnetic element. 
     
     
         29 . The method of  claim 19  wherein the step of providing a fluid suspension in a fluid chamber comprises the steps of:
 providing a fluid, target bioentities and bystander bioentities and magnetizable particles; and 
 labeling the target bioentities with the magnetizable particles. 
 
     
     
         30 . (canceled)