title: A microfluidic platform with digital readout and ultra-low detection limit for quantitative point-of-care diagnostics.
abstract: Quantitative assays are of great importance for point-of-care (POC) diagnostics because they can offer accurate information on the analytes. However, current POC devices often require an accessory instrument to give quantitative readouts for protein biomarkers, especially for those at very low concentration levels. Here, we report a microfluidic platform, the digital volumetric bar-chart chip (DV-chip), for quantitative POC diagnostics with ultra-low detection limits that are readable with the naked eye. Requiring no calibration, the DV-chip presents a digital ink bar chart (representing multiple bits composed of 0 and 1) for the target biomarker based on direct competition between O2 generated by the experimental and control samples. The bar chart clearly and accurately defines target concentration, allowing identification of disease status. For the standard PtNP solutions, the detection limit of the platform is approximately 0.1 pM and the dynamic range covers four orders of magnitude from 0.1 to 1000 pM. CEA samples with concentrations of 1 ng mL(-1) and 1.5 ng mL(-1) could be differentiated by the device. We also performed the ELISA assay for B-type natriuretic peptide (BNP) in 20 plasma samples from heart failure patients and the obtained on-chip data were in agreement with the clinical results. In addition, BNP was detectable at concentrations of less than 5 pM, which is three orders of magnitude lower than the detection limit of the previously reported readerless digital methods. By the integration of gas competition, volumetric bar chart, and digital readout, the DV-chip possesses merits of portability, visible readout, and ultra-low detection limit, which should offer a powerful platform for quantitative POC diagnostics in clinical settings and personalized detection.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA. lqin@houstonmethodist.org.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Xuan
authors.forename: Yujun
authors.initials: Y
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Lidong
authors.initials: L
authors.lastname: Qin
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D019095:Point-of-Care Systems
chemical_list: D015415:Biomarkers; D002272:Carcinoembryonic Antigen; D020097:Natriuretic Peptide, Brain