Ultrasensitive dopamine detection with crumpled graphene field-effect-transistor (grFETs) on nano-corrugated silicon chip platform

Introduction: Field-effect-transistor biosensors (BioFETs) allow for label-free detection with low limit of detection (LoD) and the potential to be integrated into lab-on-a-chip systems for large-scale multiplexing, making them a strong candidate for point-of-care (PoC) applications. However, Debye screening is a fundamental problem for all BioFETs, as the Debye length under physiological conditions is less than 1 nm while the size of antibodies/aptamers for analytes binding is at tens of nm, limiting the detectable region to the sensing channel. A promising strategy to extend the Debye length is through three-dimensional nano-corrugation, with recent demonstration of crumpled graphene-based FET (grFET) with 10 zM LoD for DNA sensing. However, there are some limitations of these crumpled grFETs created by deforming polystyrene substrates. Firstly, polystyrene is incompatible with many organic solvents commonly used in patterning processes, limiting its potential for scalability and miniaturization for multichannel measurement applications. Secondly, the heating-induced crumpling process is less reliable for mass fabrication. These limitations call for crumpled FETs fabrication in a more reliable and scalable way with processable materials and methods.

Materials and

Methods: In this research, we laid out a reliable fabrication process for realizing crumpled grFET on SiOx/Si substrates, performed characterization of the surface roughness and strain, and demonstrated dopamine detection. Figure 1 shows the schematics of a flat grFET and a crumpled grFET based on SiOx/Si substrates. To fabricate crumpled grFETs, we developed an etching protocol to obtain rough oxide surfaces with desirable roughness (Rq~4nm) through CF4/O2 reactive ion etching. Then, we transferred large-area chemical vapor deposition-grown graphene onto rough SiOx/Si substrates and used silver paint as source and drain electrodes. To characterize crumpled graphene, we used Atomic Force Microscopy (AFM) to characterize the surface roughness and graphene conformation on SiOx/Si. We also used Raman spectroscopy to reveal the impact of morphology on the strain and doping of the graphene. For dopamine detection, Ids-Vg curve was measured using electrolyte-gating in 0.1x PBS. We measured the graphene Dirac point position shift versus dopamine concentration.

Results, Conclusions, and Discussions: Our study aimed to realize grFET on nano-corrugated silicon chip platform for ultrasensitive detection. AFM results with similar Rq before and after graphene transfer showed that the graphene maintained good conformation with substrates while tailoring the roughness from 0.2 nm (flat) to 4.7 nm. As shown in Figure 2, Raman spectroscopy results on 4 regions with difference roughness indicated that increasing roughness induces increasing redshifts of both G mode and 2D mode positions. By applying vector decomposition of the peak shifts, we quantified the local strain and doping in the graphene. As the roughness increased, the Raman modes shifted along the strain axis and didn’t significantly change along the doping axis. A substrate roughness of Rq = 4.7 nm increased the tensile strain in the graphene by 0.28 ± 0.11 %, and the p-doping by -0.21 ± 3.02 e12 cm-2 .
For dopamine detection, we recorded Dirac peak position shift versus dopamine concentration from 1 aM to 10 uM for crumpled grFETs (Rq~4nm) and flat grFETs (Rq ~ 0.2 nm) and analyzed the performance, focusing on two parameters: LoD and sensing range. As shown in Figure 3, the crumpled grFETs exhibited a LoD = 10 aM, and a dynamic range from 10 aM to 10 nM. The flat grFETs exhibited LoD =1 pM and a dynamic range from 1 pM to 10 nM. Thus, crumpled grFETs on rough SiOx/Si substrate improved the LoD by 5 orders of magnitude and expanded the dynamic range down to 10 aM with the same 10 nM upper limit. In comparison, crumpled grFET with deformed polymer substrates exhibited a LoD of 25 aM and a dynamic range from 25 aM to 2.5 nM for dopamine detection. Thus, we realized crumpled grFET biosensors on nano-corrugated hard substrates while exhibiting similar sensitivity to those on polymer substrates. Besides, this is a universal ultrasensitive sensing platform working for various analytes. Overall, this study provides a guide for integrating ultrasensitive grFET biosensor onto silicon biochips. We believe that the application of our sensing platform could be beneficial for real-world PoC testing, offering quick results, enhanced signal, and multichannel capabilities.

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