High-Throughput Immunomagnetic Cell Detection Using a Microaperture Chip System

We report a microchip system based on a combination of immunomagnetic separation, microfluidics, and size-based filtration for high-throughput detection of rare cells. In this system, target cells bind to magnetic beads in vitro and flow parallel to a microchip with flow rates of milliliters/minute. A magnetic field draws the bead-bound cells toward the microchip, which contains apertures that allow passage of unbound beads while trapping the target cells. The cells captured on the chip can be investigated clearly under a microscope and released from the chip for further analysis. We first characterize the system by detecting cancer cell lines (MCF-7 and A549) in culture media. We then demonstrate detection of 100 MCF-7 cells spiked in 7.5 mL of human blood to simulate detection of circulating tumor cells present in cancer patient blood samples. On average, 85% of the spiked cells were detected. We expect this system to be highly useful in a wide variety of clinical as well as other applications that seek rare cells.

[1]  Mehmet Toner,et al.  Inertial Focusing for Tumor Antigen–Dependent and –Independent Sorting of Rare Circulating Tumor Cells , 2013, Science Translational Medicine.

[2]  Peng Li,et al.  Probing circulating tumor cells in microfluidics. , 2013, Lab on a chip.

[3]  Mo Chao Huang,et al.  Microsieve lab-chip device for rapid enumeration and fluorescence in situ hybridization of circulating tumor cells. , 2012, Lab on a chip.

[4]  D. Matei,et al.  Micro-aperture chip system for high-throughput immunomagnetic cell detection , 2012, 2012 IEEE Sensors.

[5]  J. Uhr,et al.  Challenges in the Enumeration and Phenotyping of CTC , 2012, Clinical Cancer Research.

[6]  Donald E Ingber,et al.  A combined micromagnetic-microfluidic device for rapid capture and culture of rare circulating tumor cells. , 2012, Lab on a chip.

[7]  Yu Sun,et al.  Microfluidic approaches for cancer cell detection, characterization, and separation. , 2012, Lab on a chip.

[8]  Maciej Zborowski,et al.  Rare cell separation and analysis by magnetic sorting. , 2011, Analytical chemistry.

[9]  M. Takao,et al.  Enumeration, characterization, and collection of intact circulating tumor cells by cross contamination‐free flow cytometry , 2011, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[10]  Bo Lu,et al.  3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood , 2011, Biomedical microdevices.

[11]  Yu-Hwa Lo,et al.  Review Article: Recent advancements in optofluidic flow cytometer. , 2010, Biomicrofluidics.

[12]  K. Isselbacher,et al.  Isolation of circulating tumor cells using a microvortex-generating herringbone-chip , 2010, Proceedings of the National Academy of Sciences.

[13]  Tomoko Yoshino,et al.  Size-selective microcavity array for rapid and efficient detection of circulating tumor cells. , 2010, Analytical chemistry.

[14]  M. Alunni-Fabbroni,et al.  Circulating tumour cells in clinical practice: Methods of detection and possible characterization. , 2010, Methods.

[15]  Unyoung Kim,et al.  Simultaneous sorting of multiple bacterial targets using integrated dielectrophoretic-magnetic activated cell sorter. , 2009, Lab on a chip.

[16]  Unyoung Kim,et al.  Multitarget magnetic activated cell sorter , 2008, Proceedings of the National Academy of Sciences.

[17]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[18]  Siyang Zheng,et al.  Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells. , 2007, Journal of chromatography. A.

[19]  Paul H. Bessette,et al.  Marker-specific sorting of rare cells using dielectrophoresis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.