03145nas a2200397   4500000000100000000000100001008004100002260001500043653002800058653002300086653002600109653002800135653002100163653002000184653001800204653003800222653001100260653003000271653000900301653003900310653003400349653002500383653003100408100001600439700002700455700001300482700001800495700002100513700001300534700001600547245012200563300001000685490000700695520203100702022001402733       2014                            d  c2014-01-0710aAntibodies, Immobilized10aAntigens, Neoplasm10aAntineoplastic Agents10aCell Adhesion Molecules10aCell Line, Tumor10aCell Separation10aCell Survival10aEpithelial Cell Adhesion Molecule10aHumans10aLeukocyte Common Antigens10aMale10aMicrofluidic Analytical Techniques10aNeoplastic Cells, Circulating10aPancreatic Neoplasms10aTomography, X-Ray Computed1 aWeian Sheng1 aOlorunseun O. Ogunwobi1 aTao Chen1 aJinling Zhang1 aThomas J. George1 aChen Liu1 aZ. Hugh Fan00aCapture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip  a89-980 v143 aCirculating tumor cells (CTCs) from peripheral blood hold important information for cancer diagnosis and disease monitoring. Analysis of this "liquid biopsy" holds the promise to usher in a new era of personalized therapeutic treatments and real-time monitoring for cancer patients. But the extreme rarity of CTCs in blood makes their isolation and characterization technologically challenging. This paper reports the development of a geometrically enhanced mixing (GEM) chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody-coated surfaces. With the optimized channel geometry and flow rate, the capture efficiency reached >90% with a purity of >84% when capturing spiked tumor cells in buffer. The system was further validated by isolating a wide range of spiked tumor cells (50-50,000) in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process. Furthermore, we applied the device for detecting CTCs from metastatic pancreatic cancer patients' blood; and CTCs were found from 17 out of 18 samples (>94%). We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC numbers correlated with the clinical computed tomograms (CT scans) of tumors. The presented technology shows great promise for accurate CTC enumeration, biological studies of CTCs and cancer metastasis, as well as for cancer diagnosis and treatment monitoring.  a1473-0189