Few-Layer MoS₂ Photodetector Arrays for Ultrasensitive On-Chip Enzymatic Colorimetric Analysis

Enzymatic colorimetric analysis of metabolites provides signatures of energy conversion and biosynthesis associated with disease onsets and progressions. Miniaturized photodetectors based on emerging two-dimensional transition metal dichalcogenides (TMDCs) promise to advance point-of-care diagnosis employing highly sensitive enzymatic colorimetric detection. Reducing diagnosis costs requires a batched multisample assay. The construction of few-layer TMDC photodetector arrays with consistent performance is imperative to realize optical signal detection for a miniature batched multisample enzymatic colorimetric assay. However, few studies have promoted an optical reader with TMDC photodetector arrays for on-chip operation. Here, we constructed 4 × 4 pixel arrays of miniaturized molybdenum disulfide (MoS₂) photodetectors and integrated them with microfluidic enzyme reaction chambers to create an optoelectronic biosensor chip device. The fabricated device allowed us to achieve arrayed on-chip enzymatic colorimetric detection of d-lactate, a blood biomarker signifying the bacterial translocation from the intestine, with a limit of detection that is 1000-fold smaller than the clinical baseline, a 10 min assay time, high selectivity, and reasonably small variability across the entire arrays. The enzyme (Ez)/MoS₂ optoelectronic biosensor unit consistently detected d-lactate in clinically important biofluids, such as saliva, urine, plasma, and serum of swine and humans with a wide detection range (10^-3-10³ μg/mL). Furthermore, the biosensor enabled us to show that high serum d-lactate levels are associated with the symptoms of systemic infection and inflammation. The lensless, optical waveguide-free device architecture should readily facilitate development of a monolithically integrated hand-held module for timely, cost-effective diagnosis of metabolic disorders in near-patient settings.