Devices and methods for magnetic isolation and analysis of rare cells

Abstract

An embodiment in accordance with the present invention provides two devices for the isolation of rare cell populations such as circulating tumor cells (CTCs). Both devices use magnetic fields to manipulate cells that are bounded to paramagnetic particles (PMP). One device uses surface tension and a sieve for cell filtration, whereas the other allows for the direct transfer of cells onto a standard microscope slide. Subsequent processing steps may be directly performed on the devices thereby minimizing cell losses. The first device is referred to as the ST (surface tension) device and the second device is referred to as the DT (direct transfer) device. The ST device can also be considered as a chip for the isolation of the rare cell populations.

1 . A device for isolation of a rare cell population comprising:
 a surface tension device configured for isolating the rare cell population having a well for receiving a solution containing the rare cell population;   a removable sieve configured to be disposed within the output well for collecting the rare cell population for transfer to a slide; and   a mechanism of extracting the solution from the output well downstream of the sieve.   
     
     
         2 . The device of  claim 1  further comprising a magnet for isolating the rare cell population. 
     
     
         3 . The device of  claim 1  further comprising a paramagnetic particle configured for binding cells within the rare cell population. 
     
     
         4 . A device for isolation of a rare cell population comprising:
 a direct transfer device configured for isolating the rare cell population having an input well for receiving a solution containing the rare cell population; and   a collecting surface configured for collecting cells from the rare cell population of the input well.   
     
     
         5 . The device of  claim 4  further comprising a mechanism for holding the collecting surface in a position relative to the input well. 
     
     
         6 . The device of  claim 4  further comprising a magnetic source for isolating the rare cell population. 
     
     
         7 . The device of  claim 4  further comprising a paramagnetic particle configured for binding cells within the rare cell population. 
     
     
         8 . The device of  claim 4  wherein a paramagnetic particle is mixed magnetically within the input well. 
     
     
         9 . The device of  claim 6  further comprising the magnetic source being configured to apply a magnetic force for collecting the rare cells from the input well directly onto the collecting surface. 
     
     
         10 . The device of  claim 4  further comprising a collecting device configured to attach to the collecting surface. 
     
     
         11 . The device of  claim 4  further comprising a collecting device and the input well configured such that both the collecting device and the input well can attach concurrently to the collecting surface and may be detached independent of one another. 
     
     
         12 . A method of collecting rare cells comprising:
 sequentially attaching a collecting surface to an input well;   mixing a solution of paramagnetic particles magnetically with a magnetic source;   attaching a collecting device;   transferring the magnetic source on a side of the collecting device; and   removing the input well, in order to transfer the rare cells onto the collecting surface under a magnetic force provided by the magnetic source.   
     
     
         13 . The method of  claim 12  further comprising magnetically fixing the rare cells on the collecting surface for further processing. 
     
     
         14 . The method of  claim 12  further comprising isolating the rare cell population with a magnet. 
     
     
         15 . The method of  claim 12  further comprising binding cells within the rare cell population with paramagnetic particles. 
     
     
         16 . The method of  claim 15  further comprising mixing the paramagnetic particle solution magnetically within the input well. 
     
     
         17 . The method of  claim 14  further comprising applying magnetic force for collecting the rare cells from the input well directly onto the collecting surface. 
     
     
         18 . The method of  claim 12  further comprising attaching a collecting device to the collecting surface. 
     
     
         19 . The method of  claim 12  further comprising concurrently attaching a collecting device and the input well to the collecting surface and may be detached independent of one another. 
     
     
         20 . The method of  claim 12  further comprising isolating the rare cell population using a surface tension device having a well for receiving a solution containing the rare cell population. 
     
     
         21 . The method of  claim 12  further comprising positioning a removable sieve configured to be disposed within the output well for collecting the rare cell population for transfer to a slide.