On-chip actuation transmitter for enhancing the dynamic response of cell manipulation using a macro-scale pump.

An on-chip actuation transmitter for achieving fast and accurate cell manipulation is proposed. Instead of manipulating cell position by a directly connected macro-scale pump, polydimethylsiloxane deformation is used as a medium to transmit the actuation generated from the pump to control the cell position. This actuation transmitter has three main advantages. First, the dynamic response of cell manipulation is faster than the conventional method with direct flow control based on both the theoretical modeling and experimental results. The cell can be manipulated in a simple harmonic motion up to 130 Hz by the proposed actuation transmitter as opposed to 90 Hz by direct flow control. Second, there is no need to fill the syringe pump with the sample solution because the actuation transmitter physically separates the fluids between the pump and the cell flow, and consequently, only a very small quantity of the sample is required (<1 μl). In addition, such fluid separation makes it easy to keep the experiment platform sterilized because there is no direct fluid exchange between the sample and fluid inside the pump. Third, the fabrication process is simple because of the single-layer design, making it convenient to implement the actuation transmitter in different microfluidic applications. The proposed actuation transmitter is implemented in a lab-on-a-chip system for red blood cell (RBC) evaluation, where the extensibility of red blood cells is evaluated by manipulating the cells through a constriction channel at a constant velocity. The application shows a successful example of implementing the proposed transmitter.

[1]  Young-Ho Cho,et al.  A continuous cell separation chip using hydrodynamic dielectrophoresis (DEP) process , 2005 .

[2]  Katsuo Kurabayashi,et al.  Recent advancements in optofluidics-based single-cell analysis: optical on-chip cellular manipulation, treatment, and property detection. , 2014, Lab on a chip.

[3]  Fumihito Arai,et al.  High Resolution Cell Positioning Based on a Flow Reduction Mechanism for Enhancing Deformability Mapping , 2014, Micromachines.

[4]  Jie Xu,et al.  The effects of 3D channel geometry on CTC passing pressure--towards deformability-based cancer cell separation. , 2014, Lab on a chip.

[5]  Valentina Preziosi,et al.  Microfluidics analysis of red blood cell membrane viscoelasticity. , 2011, Lab on a chip.

[6]  Fumihito Arai,et al.  A New Dimensionless Index for Evaluating Cell Stiffness-Based Deformability in Microchannel , 2014, IEEE Transactions on Biomedical Engineering.

[7]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[8]  Chang Liu,et al.  Re-configurable fluid circuits by PDMS elastomer micromachining , 1999, Technical Digest. IEEE International MEMS 99 Conference. Twelfth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.99CH36291).

[9]  H. Madarame,et al.  Velocity measurement of both red blood cells and plasma of in vitro blood flow using high-speed micro PIV technique , 2005 .

[10]  Justin C. Williams,et al.  Microfluidics-based devices: New tools for studying cancer and cancer stem cell migration. , 2011, Biomicrofluidics.

[11]  Luke P. Lee,et al.  Toward Integrated Molecular Diagnostic System ($i$ MDx): Principles and Applications , 2014, IEEE Transactions on Biomedical Engineering.

[12]  I D Johnston,et al.  Whole blood pumping with a microthrottle pump. , 2010, Biomicrofluidics.

[13]  Fumihito Arai,et al.  Red blood cell fatigue evaluation based on the close-encountering point between extensibility and recoverability. , 2014, Lab on a chip.

[14]  Nicole K Henderson-Maclennan,et al.  Deformability-based cell classification and enrichment using inertial microfluidics. , 2011, Lab on a chip.

[15]  Wei-Hua Huang,et al.  A micropillar‐integrated smart microfluidic device for specific capture and sorting of cells , 2007, Electrophoresis.

[16]  Fumihito Arai,et al.  Geometrical alignment for improving cell evaluation in a microchannel with application on multiple myeloma red blood cells , 2014 .

[17]  Nathan Cermak,et al.  Characterizing deformability and surface friction of cancer cells , 2013, Proceedings of the National Academy of Sciences.

[18]  Won Gu Lee,et al.  Cell manipulation in microfluidics , 2013, Biofabrication.

[19]  David Sinton,et al.  Hand-powered microfluidics: A membrane pump with a patient-to-chip syringe interface. , 2012, Biomicrofluidics.

[20]  Yen-Heng Lin,et al.  A negative-pressure-driven microfluidic chip for the rapid detection of a bladder cancer biomarker in urine using bead-based enzyme-linked immunosorbent assay. , 2013, Biomicrofluidics.