Microfluidic cell concentrator with a reduced-deviation-flow herringbone structure.

In this study, a microfluidic cell concentrator with a reduced-deviation-flow herringbone structure is proposed. The reduced-deviation-flow herringbone structure reduces the magnitude of deviation flow by a factor of 3.3 compared to the original herringbone structure. This structure shows higher recovery efficiency compared to the original herringbone structure for various particle sizes at high flow rate conditions. Using the reduced-deviation-flow herringbone structure, the experimental results show a recovery efficiency of 98.5% and a concentration factor of 3.4× at a flow rate of 100 ml/h for all particle sizes. An iterative concentration process is performed to achieve a higher concentration factor for 10.2-µm particles and Jurkat cells. With two stages of the concentration process, we were able to achieve over 98% recovery efficiency and a concentration factor of 10-11×. Cell viability was found to be above 96% after iterative concentration. We believe that this device could be used to concentrate cells as a preparatory step for studying low-abundance cells.

On-chip Extraction of Intracellular Molecules in White Blood Cells from Whole Blood.

The extraction of virological markers in white blood cells (WBCs) from whole blood--without reagents, electricity, or instruments--is the most important first step for diagnostic testing of infectious diseases in resource-limited settings. Here we develop an integrated microfluidic chip that continuously separates WBCs from whole blood and mechanically ruptures them to extract intracellular proteins and nucleic acids for diagnostic purposes. The integrated chip is assembled with a device that separates WBCs by using differences in blood cell size and a mechanical cell lysis chip with ultra-sharp nanoblade arrays. We demonstrate the performance of the integrated device by quantitatively analyzing the levels of extracted intracellular proteins and genomic DNAs. Our results show that compared with a conventional method, the device yields 120% higher level of total protein amount and similar levels of gDNA (90.3%). To demonstrate its clinical application to human immunodeficiency virus (HIV) diagnostics, the developed chip was used to process blood samples containing HIV-infected cells. Based on PCR results, we demonstrate that the chip can extract HIV proviral DNAs from infected cells with a population as low as 10(2)/µl. These findings suggest that the developed device has potential application in point-of-care testing for infectious diseases in developing countries.