Label-free impedance detection of low levels of circulating endothelial progenitor cells for point-of-care diagnosis

• Published in: Biosensors & bioelectronics 2010-01, Vol.25 (5), p.1095-1101
• Main Authors: Ng, Shi Yun, Reboud, Julien, Wang, Karen Y.P., Tang, Kum Cheong, Zhang, Li, Wong, Philip, Moe, Kyaw Thu, Shim, Winston, Chen, Yu
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biosensing Techniques - instrumentation; Biotechnology; Cell Count - instrumentation; Cell Separation - instrumentation; Dielectrophoresis; Electrophoresis - instrumentation; Endothelial Cells - cytology; Endothelial progenitor cells; Equipment Design; Equipment Failure Analysis; Fundamental and applied biological sciences. Psychology; Humans; Immunoassay - instrumentation; Impedance spectroscopy; Integrated cell-based detection; Microfluidic Analytical Techniques - instrumentation; Point-of-care diagnosis; Point-of-Care Systems; Reproducibility of Results; Sensitivity and Specificity; Staining and Labeling; Stem Cells - cytology
• ISSN: 0956-5663; 1873-4235
• DOI: 10.1016/j.bios.2009.09.031

This paper presents a novel microfluidic system for rapid label-free detection of endothelial progenitor cells (EPCs) from small volumes of white blood cells samples, to obtain a bedside cardiovascular diagnostic solution. The system was built on a single 1 cm 2 microelectrode array silicon chip, integrated with negative dielectrophoresis for cell trapping, surface immunochemistry for selective cell capture, and fluidics for cell washing and impedance detection. The level of circulating EPC level in blood is a biomarker of clinical interest, linked to the assessment of risk factors in cardiovascular diseases which are a major global concern. Rare EPCs are usually detected through in vitro culture or flow cytometry, which are too time-consuming to bring timely reports in acute diseases. Although microfluidics approaches have enabled reduced processing time and enhanced portability, their sensitivity and processing volumes are still inadequate for rare cell detection at a bedside setting. Using small highly sensitive microelectrodes, our novel integrated system achieved the detection of 720 EPCs in a small 12 μl sample of 72,000 peripheral blood mononuclear cells (PBMC), i.e. equivalent to a concentration of EPCs of 0.1% of 100 μl blood. This demonstrated that clinically significant level of EPCs (