Few-Layer MoS₂Photodetector Arrays for Ultrasensitive On-Chip Enzymatic Colorimetric Analysis

Abstract

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.

Recent Progress on Two-Dimensional Materials

“…Since the intrinsic enzyme mimetic activity of magnetite (Fe3O4) was discovered by Yan and co-worker, "nanoenzyme" have been received more and more scientists' recognition 1428 . The intrinsic peroxidase-like activity of carboxyl-modified graphene oxide (GO-COOH) was firstly reported by Song et al 1429 , 2D materials with peroxidase-like, glucose oxidase-like catalytic activities have aroused the interest of researchers in the construction of colorimetric sensors, including MoS2, WS2, Rh and g-C3N4 [1430][1431][1432][1433] To improve the sensitivity of colorimetric sensing platforms, formation of 2D materials-based nanocomposites becomes a popular method. Generally, 2D materials-based nanocomposites bring better performances due to the synergistic effect of 2D materials and functionalized groups.…”

Nanomaterials‐assisted metabolic analysis toward in vitro diagnostics

“…[ 72 ] Notably, there were some exciting attempts that combined microfluidic systems with colorimetric assays to enable simultaneous metabolite detection. [ 73,74 ] Park et al. fabricated an optoelectronic biosensor chip by integrating the microarrayed MoS 2 with microfluidic chambers for enzymatic reaction, allowing the colorimetric detection of lactate with LOD of 0.51 ng mL –1 .…”

“…fabricated an optoelectronic biosensor chip by integrating the microarrayed MoS 2 with microfluidic chambers for enzymatic reaction, allowing the colorimetric detection of lactate with LOD of 0.51 ng mL –1 . [ 74 ] In addition, Phinheiro et al. developed a microfluidic paper‐based analytical device relying only on the plasmonic transduction of Au NPs and further improved the accessibility and cost‐efficiency of colorimetric assays.…”

“…[70] Colorimetry features visual detection of metabolites via color variations or UV absorption spectrum without complicated equipment. [72][73][74] The functionalized noble metals like Au offer the intrinsic peroxidase-like activity, which promotes superoxide anion formation and electron transfer and can be exploited for colorimetric assays. For example, the phosphatecontaining metabolites can be detected by blocking the superoxide anion production and related electron transfer process.…”

“…[72] Notably, there were some exciting attempts that combined microfluidic systems with colorimetric assays to enable simultaneous metabolite detection. [73,74] Park et al fabricated an optoelectronic biosensor chip by integrating the microarrayed MoS 2 with microfluidic chambers for enzymatic reaction, allowing the colorimetric detection of lactate with LOD of 0.51 ng mL -1 . [74] In addition, Phinheiro et al developed a microfluidic paper-based analytical device relying only on the plasmonic transduction of Au NPs and F I G U R E  (A) Schematic illustration of a fluorescence-based sensing system by using nitrogen-doped graphene quantum dot as the fluorescence probe.…”