Cell Density Detector Based on Light Beam Focusing

Although the lab-on-a-chip system has been successfully applied in a wide variety of fields, the goal of achieving a cell counter with simple operation, low cost, and high accuracy still attracts continuous research efforts. In this paper, the authors explore a cell counter based on light beam focusing to measure the density of adherent cells. In this sensor, the light emitted from the optical fibers is collimated by the collimating lens formed in polydimethylsiloxane (PDMS). The uniformly attached adherent cells act as a convex lens, focusing the collimated light propagated through them. The intensity of the focused light indicates the density of the adherent cells. For Hela cells, a detection limit of 8.3 × 104 cells/mL with a detection range from 0.1 × 106 cells/mL to 1.0 × 106 cells/mL is achieved. This sensor is particularly useful for drug screening, cell pathology analysis, and cancer pre-diagnosis.

[1]  P. Gourley Biocavity laser for high-speed cell and tumour biology , 2003 .

[2]  Marlies Brinkmann,et al.  New technologies for automated cell counting based on optical image analysis `The Cellscreen' , 2004, Cytotechnology.

[3]  O. C. Blair,et al.  Practical Flow Cytometry , 1985, The Yale Journal of Biology and Medicine.

[4]  C. Reutelingsperger,et al.  Flow cytometry of apoptotic cell death. , 2000, Journal of immunological methods.

[5]  C. Heusser,et al.  Detection of intracellular cytokines by flow cytometry. , 1993, Journal of immunological methods.

[6]  C. Ying,et al.  Relationship of somatic cell count, physical, chemical and enzymatic properties to the bacterial standard plate count in dairy goat milk , 2002 .

[7]  Judith S Eisen,et al.  Characterization of enteric neurons in wild-type and mutant zebrafish using semi-automated cell counting and co-expression analysis. , 2013, Zebrafish.

[8]  G. Kretzmer Influence of stress on adherent cells. , 2000, Advances in biochemical engineering/biotechnology.

[9]  Giuseppe Nunnari,et al.  A cellular neural network based system for cell counting in culture of biological cells , 1998, Proceedings of the 1998 IEEE International Conference on Control Applications (Cat. No.98CH36104).

[10]  Peter Russer,et al.  The Transmission Line Matrix Method , 2000 .

[11]  G. Whitesides,et al.  Soft Lithography. , 1998, Angewandte Chemie.

[12]  Zhang Ji-long,et al.  Study on the Relational Expression of Solution Concentration and Its Refractive Index , 2009 .

[13]  Hirokazu Taniguchi,et al.  Reduction of speckle contrast in multimode fibers using piezoelectric vibrator , 2014, Photonics West - Lasers and Applications in Science and Engineering.

[14]  Xudong Fan,et al.  On the performance quantification of resonant refractive index sensors. , 2008, Optics express.

[15]  Min Cheol Park,et al.  Soft lithography for microfluidics: a review , 2008 .

[16]  B S Bull,et al.  Platelet counts with the Coulter counter. , 1965, American journal of clinical pathology.

[17]  S. Falkow,et al.  Bacterial genetics by flow cytometry: rapid isolation of Salmonella typhimurium acid‐inducible promoters by differential fluorescence induction , 1996, Molecular microbiology.

[18]  W. Yunus,et al.  Refractive index of solutions at high concentrations. , 1988, Applied optics.

[19]  M. Spanô,et al.  Flow cytometry applications in the evaluation of sperm quality: semen analysis, sperm function and DNA integrity. , 2005, Contraception.

[20]  D. Frank Culture of Animal Cells: A Manual of Basic Technique , 1984, The Yale Journal of Biology and Medicine.

[21]  M. Despont,et al.  SU-8: a low-cost negative resist for MEMS , 1997 .

[22]  V. Tuchin,et al.  The refractive index of human hemoglobin in the visible range , 2011, Physics in medicine and biology.

[23]  Carlo Edoardo Campanella,et al.  Label-free optical resonant sensors for biochemical applications , 2013 .

[24]  Timothy D. Smith,et al.  Accurate measurement of peripheral blood mononuclear cell concentration using image cytometry to eliminate RBC-induced counting error. , 2013, Journal of immunological methods.

[25]  Y. Jung,et al.  Speckle reduction in multimode fiber with a piezoelectric transducer in radial vibration for fiber laser marking and display applications , 2008, SPIE LASE.

[26]  G. Whitesides,et al.  Soft lithographic methods for nano-fabrication , 1997 .

[27]  B. S. Manjunath,et al.  Automated tool for the detection of cell nuclei in digital microscopic images: application to retinal images. , 2006, Molecular vision.

[28]  Kelly P. Smith,et al.  Basic pluripotent stem cell culture protocols , 2012 .

[29]  T. Denny,et al.  Evaluation of a method for counting absolute numbers of cells with a flow cytometer , 1997, Clinical and diagnostic laboratory immunology.

[30]  D. Di Carlo,et al.  Sheathless inertial cell ordering for extreme throughput flow cytometry. , 2010, Lab on a chip.

[31]  Joan Carletta,et al.  A micromachined high throughput Coulter counter for bioparticle detection and counting , 2007 .

[32]  S. Ingham,et al.  Correlation between standard plate count and somatic cell count milk quality results for Wisconsin dairy producers. , 2014, Journal of dairy science.

[33]  Alan G. R. Evans,et al.  Design and fabrication of a micromachined Coulter counter , 1999 .

[34]  J M Anderson,et al.  Influence of biomaterial surface chemistry on the apoptosis of adherent cells. , 2001, Journal of biomedical materials research.