(Invited) Multiplexed Label-Free Biosensing Using 2D-Heterostructures: Materials Stability and Signal Uniformity
Authors: Rotkin Slava V. , Ignatova Tetyana 
Published: July 2022

Two-dimensional materials (2DM) has been already applied for bio- and chemical sensing[1],[2]. Even individual 2D materials often outperform bulk analogues, showing strong response and being compatible with flexible technologies, thus opening horizons for wearable and Point-of-Care applications[3]. Most recently, emergent need to achieve better, more precise and sensitive drug detection in medicine and health care has been addressed by developing new types of biosensors[4]. Extending properties of individual 2DMs by constructing their van der Waals heterostructures, either lateral or vertical, offers new response and/or transduction mechanisms and further improvement of device performance. Such heterostructures have potential for label-free biosensing and could be designed and/or integrated together to generate several signals in response to a single analyte. Such a capability enables a multimodal detection, which exceeds single-mode biosensing through its higher throughput, as well as by better ability to differentiate the analyte from background signals in a complex media, and potentially allows multiplexing (responding by several channels to a group of substances in parallel).
Despite significant efforts were invested into discovery of newer and better 2D materials with biosensing capabilities, there is only limited knowledge of factors that could limit its performance. Indeed, atomically thin 2D materials have an ultimate surface-to-volume ratio which helps sensing, but may result in surface non-uniformities at the nanometer scale such as: atomic impurities, adsorbates, single atom and lattice defects, wrinkles and ruptures – to name just a few. Such defects may modulate their sensing properties. Here, a new multidimensional optical imaging technique will be presented which is capable to detect lattice mismatch and work function difference in the heterostructure material. Those result in strain and charge transfer and vary optical response at the nanometer scale, hard to detect and study by normal characterization tools.
We present a vertical heterostructure comprised of monolayer graphene and single layer flakes of MoS2. An optical label-free detection of doxorubicin, a common cancer drug, is reported via three independent optical detection channels (photoluminescence shift, Raman shift and Graphene Enhanced Raman Scattering). Non-uniform broadening of components of multimodal signal correlates with the statistical distribution of local optical properties of the 2DM heterostructure. It will be shown how mapping of distribution for doping and strain (taken with sub-diffractional resolution) allows one to understand the role of those for modulation of electronic properties of 2D material.
Acknowledgement: partial support is acknowledged from NSF CHE-2032582, CHE-2032601, DMR-1539916 and DMR-2011839 grants.

[1] Oh, S.-H.; et.al, Nature Communications 2021, 12, 3824.

[2] Bolotsky, A.; et.al, ACS Nano 2019, 13, 9781.

[3] Pang, Y.; et.al, Small 2020, 16, 1901124.

[4] Moradi, R; Small (2021). doi: 10.1002/smll.202104847