Parallel optofluidic detection of multiple cardiac biomarkers for point-of-care testing applications

Abstract

Point-of-care testing (POCT), which enables personalized, accurate, affordable, and accessible medical services, is indispensable in the diagnostics, screening, and treatment of disease, especially for emergency and severe cases. Considering the complexity of disease, multiplexed point-of-care (MPOC) testing is very important for the simultaneous detection of several biomarkers to improve accuracy and increase analysis throughput. In this work, a microfiber interferometer based multiplexed optofluidic (MIMO) chip sensor is proposed for multiplexed, quantitative detection of cardiac biomarkers. Four microfiber interferometers are suspended and fixed in four separate microscale sample channels of an imprinted polydimethylsiloxane (PDMS) chip. A drop of the sample is distributed into the four parallel channels automatically and reacts with the probe on the microfiber sensor surface specifically, which leads to the wavelength shift of the spectrum resulting from evanescent wave interactions with biomolecules. There microfiber interferometers are functionalized with myoglobin (Myo) antibody, cardiac troponin I (cTnI) antibody, and creatine kinase–myocardial band isoenzymes (CK–MB) antibody respectively and the rest microfiber interferometer is with no functionalization, which acts as the control channel to reduce noise. By using compact dedicated commercial optical modules, miniaturized and low cost experimental setup is organized and achieve four channel simultaneous measurement through time division multiplexing. Three cardiac biomarkers, Myo, cTnI, and CK–MB, are synchronously detected on the proposed MIMO chip sensor. In a standard buffer sample, the log-linear sensing range of CK–MB is 0.2 ∼ 200 ng/mL with detection limit of 3.7 pg/mL, the log-linear sensing range of Myo is 2 ∼ 2000 ng/mL with detection limit of 0.5 ng/mL, and the log-linear sensing range of cTnI 0.02 ∼ 20 ng/mL with detection limit of 2.6 pg/mL, which all perfectly cover the actual diagnostic limit of myocardial infarction. Furthermore, the MIMO chip sensor maintains excellent performance of both specificity and detection capabilities in more complex serum samples. In double-blind trials of multiple biomarker detection, the MIMO chip sensor exhibits comparable detection ability with a commercial kit and good resistance to environmental disturbance. The proposed MIMO chip sensor sensing system offers a low-cost, portable, self-driven, and miniaturized scheme for a multiplexed point-of-care testing device, promoting the feasibility and accessibility of personalized medical services and paving the way for clinical application and industrialization.