MoS₂-enabled dual-mode optoelectronic biosensor using a water soluble variant of µ-opioid receptor for opioid peptide detection

Abstract

Owing to their unique electrical and optical properties, two-dimensional transition metal dichalcogenides have been extensively studied for their potential applications in biosensing. However, simultaneous utilization of both optical and electrical properties has been overlooked, yet it can offer enhanced accuracy and detection versitility. Here, we demonstrate a dual-mode optoelectronic biosensor based on monolayer molybdenum disulfide (MoS2) capable of producing simultaneous electrical and optical readouts of biomolecular signals. On a single platform, the biosensor exhibits a tunable photonic Fano-type optical resonance while also functioning as a field-effect transistor (FET) based on a optically transparent gate electrode. Furthermore, chemical vapor deposition grown MoS2 provides a clean surface for direct immobilization of a water-soluble variant of the μ-opioid receptor (wsMOR), via a nickel ion-mediated linker chemistry. We utilize a synthetic opioid peptide to show the operation of the electronic and optical sensing modes. The responses of both modes exhibit a similar trend with dynamic ranges of four orders of magnitude and detection limits of <1 nM. Our work explores the potential of a versatile multimodal sensing platform enabled by monolayer MoS2, since the integration of electrical and optical sensors on the same chip can offer flexibility in read-out and improve the accuracy in detection of low concentration targets.

Novel variants of engineered water soluble mu opioid receptors with extensive mutations and removal of cysteines

“…The results clearly indicate that all four of the new wsMOR‐FLs have comparable ligand binding affinity (nM range) as the variants engineered previously (which all have similar ligand binding affinities around 70 nM) 7 . Using the various biosensors developed by our group which include graphene based biosensors and surface plasmon resonance based biosensors, the determined affinities for these designed variants of wsMORs are close to the affinities for the native MOR in the lipid environment 10,16,17 . The different results in the affinity determinations are caused by differences in sensitivity, since the biosensors have high sensitivity and a high signal to noise ratio.…”

“…We wanted to know if the increase of mutated position could maintain the receptor's overall structure and ligand binding capability. In addition to the usefulness of the variants of water soluble protein that has been discussed by us and others, 9,10,16‐18 the availability of minimal cysteine variants offers several opportunities for the study of the receptor's structural and functional relationships. Recent studies have used similar approaches to study the conformational dynamics of the β 2 AR using NMR and single‐molecule fluorescence spectroscopy 19‐22 .…”

“…7 Using the various biosensors developed by our group which include graphene based biosensors and surface plasmon resonance based biosensors, the determined affinities for these designed variants of wsMORs are close to the affinities for the native MOR in the lipid environment. 10,16,17 The different results in the affinity determinations are caused by differences in sensitivity, since the biosensors have high sensitivity and a high signal to noise ratio. The key point here is that the opioid binding capacity is well-preserved, despite a massive mutation strategy for the residues on the surface of the protein, as long as the opioid binding pocket remains intact.…”

“…As compared to our recently published work on the full-length version of the wsMOR, 8 there are multiple scientific implication and applications for this new effort in addition to these we have discussed or demonstrated in the past. 6,7,9,16,17 First of all, in this is proof-of-concept, additional mutations on the surface of lipid-facing hydrophobic positions to resemble more the sequence identity of globular protein of the same size, were introduced. We wanted to know if the increase of mutated position could maintain the receptor's overall structure and ligand binding capability.…”

Harnessing selectivity in chemical sensing via supramolecular interactions: from functionalization of nanomaterials to device applications

“…Likewise graphene, most applications based on TMDs, BP, and MXenes for sensing where the recognition of analytes is achieved by (supra)molecular interactions refer to biosensors. 65,131 Noteworthy examples include TMD transistors, 132,133 electrochemical and optoelectronic devices, 134,135 and fluorescence/colorimetric indicators, BP transistors, 136,137 MXene-modified electrodes 138,139 and SPR chips 139 decorated with bioreceptors (e.g. antibodies, aptamers, etc.)…”