MEMS (Micro-Electro-Mechanical-Systems) based microfluidic platforms for magnetic cell separation

Microfluidic platforms for magnetic cell separation were developed and investigated for isolation of magnetic particles and magnetically tagged cells from a fluidic sample. Two types of magnetic separation platforms were considered: an Isodynamic Open Gradient Magnetic Sorter (OGMS) and a multistage bio-ferrograph. Miniaturized magnets were designed using magnetostatic simulation software, microfluidic channels were fabricated using microfabrication technology and magnetic separation was investigated using video microscopy and digital image processing.;The isodynamic OGMS consisted of an external magnetic circuit and a microfabricated channel (biochip). The biochip is placed inside the magnetic field of the external circuit to obtain nearly constant energy density gradient &parl0;DB2 2m0 &parr0; in the portion of the channel used for separation. A value of DB2 = 0.51+/-0.01 T2/mm was obtained over a desired location (850 microm x 250 microm) of the channel cross-section. The biochip consisted of an enclosed microfluidic channel (250 microm thick) with a set of discrete magnetic elements (120 microm thick) embedded in both sidewalls. The key challenge was to integrate enclosed microchannels on transparent substrates with electroplating molds on the both walls of the channel. The microfabrication process involved improving adhesion of SU-8 to Pyrex, forming enclosed channels using a low temperature SU-8 adhesive bonding, and fabricating patterned plating molds on both sides of the bonded wafers. Adhesion of SU-8 to Pyrex was improved by using a highly crosslinked thin SU-8 adhesion layer, and enclosed microchannels were fabricated using selectively exposed SU-8 bond formation layers. Electroplating molds were fabricated using KMPR photoresists and were integrated on both sides of the bonded wafers.;The multistage bio-ferrograph consisted of a microfabricated enclosed channel placed on the surface of a multi-unit magnet (4 trapezoidal magnets placed in series) assembly such that magnetic cells from a flowing stream would be deposited on designated locations.;The OGMS system and the multistage bio-ferrograph were tested using different concentrations (104 - 106/microL) of magnetic particles (6.4+/-0.5microm) and magnetically labeled Jurkat cells. The OGMS was able to deflect magnetic particles by 500-1000 microm and the capture efficiencies of magnetic particles and cells with the multistage bioferrograph were 80-85% and 99.5%, respectively.