title: Label-free impedance detection of low levels of circulating endothelial progenitor cells for point-of-care diagnosis.
abstract: 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 microl sample of 72,000 peripheral blood mononuclear cells (PBMC), i.e. equivalent to a concentration of EPCs of 0.1% of 100 microl blood. This demonstrated that clinically significant level of EPCs (<0.5% of PBMC) could be detected for the first time on a detection system at bedside set-up, showing great potential in applications for point-of-care diagnosis.
authors.affiliation: Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research) Singapore, Singapore Science Park II, Singapore.
authors.forename: Shi Yun
authors.initials: SY
authors.lastname: Ng
authors.forename: Julien
authors.initials: J
authors.lastname: Reboud
authors.forename: Karen Y P
authors.initials: KY
authors.lastname: Wang
authors.forename: Kum Cheong
authors.initials: KC
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Philip
authors.initials: P
authors.lastname: Wong
authors.forename: Kyaw Thu
authors.initials: KT
authors.lastname: Moe
authors.forename: Winston
authors.initials: W
authors.lastname: Shim
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D015374:Biosensing Techniques / Q000295:instrumentation; D002452:Cell Count / Q000295:instrumentation*; D002469:Cell Separation / Q000295:instrumentation*; D004586:Electrophoresis / Q000295:instrumentation; D042783:Endothelial Cells / Q000166:cytology*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D019095:Point-of-Care Systems; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology*