Symposium SB06—Graphene and Related 2D Materials for Bioelectronics and Healthcare

Cortical maps, which are indicative of cognitive status, are shaped by experience. Previous mapping tools, such as penetrating electrodes and imaging techniques, are limited in assessing high-resolution brain maps largely owing to their invasiveness and poor spatiotemporal resolution, respectively. In this talk, we developed a flexible graphene-based multichannel electrode array for electrocorticography (ECoG) recording, which enables us to assess cortical maps in a time- and labor-efficient manner. The flexible electrode array, formed by chemical vapor deposition (CVD)-grown graphene, provides low impedance and electrical noise because of the creation of a good interface between the graphene and brain tissue, which improves the detectability of neural signals. In addition, we present the results of simultaneous recordings of multiple cortical sites and responsive neurostimulations for epilepsy treatment carried out in free-moving rats. Flexible graphene-based electrode array which stably wraps onto the cortex surface of a living rat’s brain, exhibiting a superior signal-to-noise ratio. The graphene multichannel electrode successfully detected brain signals with high-throughput spatiotemporal resolution and substantially suppressed pilocarpine-induced epileptic discharges and behavior. The simultaneous recording and neurostimulation in awake animals can lead to a fundamental change in the approaches used for the treatment of medically intractable epilepsy.

Near-infrared (NIR) emissive nanomaterials are desired for bioimaging and drug delivery applications due to the high tissue penetration depth of NIR light, enabling in vitro/ex vivo/in vivo fluorescence tracking. Considering the scarcity of NIR-fluorescing biocompatible nanostructures, we have for the first-time synthesized nanometer-sized reduced graphene oxide-derived graphene quantum dots (RGQDs) with NIR (950 nm) emission highly biocompatible in vitro with no preliminary toxic response in vivo. RGQDs are obtained in a high-yield (~90%) top-down sodium hypochlorite/UV-driven synthetic process from non-emissive micron-sized reduced graphene oxide (RGO) flakes. This oxidation of RGO yields quantum dots with an average size of 3.54 ± 0.05 nm and a highly crystalline graphitic lattice structure with distinguishable lattice fringes. RGQDs exhibit excitation-independent emission in the visible and NIR-I region with a maximum NIR quantum yield of ~7%, where in situ fluorescence measurements of the synthesis also showed an interdependence of evolution for the visible and NIR-I emissions. Unlike their parent material, RGQDs show substantial biocompatibility with ~75-80% cell viability up to high (1 mg/mL) concentrations verified via both MTT and luminescence-based cytotoxicity assays. Tracked in vitro via their NIR fluorescence, RGQDs exhibit efficient internalization in HeLa cells maximized at 12 h with further anticipated excretion. In vivo, RGQDs introduced intravenously to NCr nude mice allow for fluorescence imaging in live sedated animals without the need in sacrificing those at imaging time points. Their distribution in spleen, kidneys, liver, and intestine assessed from NIR fluorescence in live mice, is further confirmed by excised organ analysis and microscopy of organ tissue slices. This outlines the potential of novel RGQDs as NIR imaging probes suitable for tracking therapeutic delivery in live animal models. A combination of smaller size, water-solubility, bright NIR emission, simple/scalable synthesis, and high biocompatibility gives RGQDs a critical advantage over a number of existing nanomaterials-based imaging platforms.

As carbon nanotubes (CNT) emerging in the healthcare and bioengineering field, it is essential to produce toxic-free, biofriendly, biocompatible, water-soluble, fewer defects, highly concentrated, and stable biological CNT solutions. We report stable and high-quality multi-walled carbon nanotube (MWCNT) dispersions using proteins as a dispersing agent by a simple stirring on the benchtop. Bovine serum albumin (BSA), anionic or cationic BSA, ovalbumin, lysozyme, and hemoglobin are used to disperse MWCNT, and the dispersions and exfoliation efficiency depended on the charge, size, and nature of the protein. We achieved a minimum dispersion limit ~5 mg/ml and a maximum up to ~12 mg/ml and the undispersed CNT is easily removed by centrifugation and washing or precipitation. The BSA-coated CNT showed controllable surface charge, stable dispersions at pH 7 to 14 and stability over a wide temperature (2–50 °C) up to 6 months. Furthermore, the CNT dispersions loaded on the cellulose filter paper to fabricate the metal-free and conductive bio-CNT films. The bio-CNT films showed a resistance of <30 Ω/sq and conductivity >10000 s/m, greater than the electrical conductivity reported for CNT-polymer composites. This general, powerful approach is used to produce environmentally benign, biocompatible CNT dispersions by a simple method that can be adapted under resource-limited conditions.
Keywords: Carbon nanotubes, protein, bio-conductivity films, biocatalysts

Two-dimensional (2D) materials have the potential to become the functional elements of future bioelectronic interfaces. So far, studies directed towards understanding their biocompatibility have mostly utilized exfoliated flakes and suspensions resulting in large uncertainty and discrepancies in their cytotoxicity measures. In this work, as a first step before incorporating them in bioelectronic interfaces, we have performed a comprehensive experimental study of in vitro cell-viability of large-scale sheets of electronics grade 2D materials that include platinum diselenide (PtSe₂), platinum ditelluride (PtTe₂), molybdenum disulfide (MoS₂), and graphene. These materials were selected because of their superior electronic and mechanical properties, and their atomically thin layered structure which facilitates efficient surface chemical functionalization. We cultured embryonic stem cells (ESCs) and ESC-derived motor neurons (MNs) on the surface of these large-area 2D sheets and quantified cell-viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the Lactate Dehydrogenase (LDH) assay. Live-dead fluorescence imaging was performed to qualitatively understand the trends in cellular growth and proliferation. The results suggest that PtSe₂ displays cell-viability values on par with those of the controls, graphene, and MoS₂. Contrarily, PtTe₂ displays the lowest cell-viability value amongst all the 2D materials when observed through the lens of the MTT assay but displays cell-viability similar to that of the controls when observed through the lens of the LDH assay. We provide experimental validations to explain for this discrepancy with PtTe₂’s cell-viability and present an overall view on how our study can be further developed to incorporate other 2D materials and cell-viability measurement assays. We believe these results from the in vitro biocompatibility experiments can help large-area 2D materials become an alternative for both future cell-culture scaffolds and bioelectronic implants.

Graphene has emerged as a novel material with enhanced electrical and structural properties that can be used for a multitude of applications from super-capacitors to biosensors.
The use of laser irradiation to induce networks of graphene-based structures towards cost effective, flexible device fabrication has been a highly pursued area, with application of laser engraving in various polymeric substrates.
In this work, we report the application of this approach towards commonly available, eco-friendly and low-cost substrates, namely office paper and cork to be used as a standard glucose biosensor and supercapacitor.
As proof-of-concept amperometric, enzymatic biosensors were developed, exhibiting a good analytical performance in physiologically relevant glucose levels in blood, with linear sensitivity range between 0.5 and 15 mM, with a limit of detection of 130 µM and a sensitivity as high as 27.23 µA/mM.
Furthermore, flexible microcapacitor has been also developed on cork exhibiting an outstanding performance with an areal capacitance of 1.39 mF cm-2 (107.26 mF cm-3) at 0.005 mA cm-2.
It was proved that is possible to join sustainable materials and low-cost techniques for laser induced graphene electrodes production, representing a mandatory step for a clean and green future in wearable and self-sustainable electronics.

Printed graphene (PG) has recently shown promise in the fabrication of low-cost, flexible electrical circuits. However, biosensing applications involving PG have been constrained due in part to low resolution printing, destructive post-print annealing steps, low electrochemical reactivity, and/or relatively smooth, planar non-electroactive surfaces.

In this presentation, we demonstrate how low-cost printed and flexible PG circuits can be fabricated and functionalized fluid transport and electrochemical sensing. First, we demonstrate how the utility of PG is expanded through high-resolution patterning, post-print laser annealing, and biorecognition agent functionalization techniques. A new graphene patterning technique [i.e., inkjet maskless lithography (IML)] is used to form high resolution, flexible graphene films (line widths down to 20 µm) that significantly exceeds current graphene inkjet printing resolution (line widths ~ 60 µm). We build upon this technique and add salt porogens into the graphene inks [i.e., salt impregnated inkjet maskless lithography (SIIML)] to increase the micro/nano surface area of the printed graphene to further improve biosensor performance. Next, a rapid pulse laser annealing technique with a continuous CO₂ laser is used to tune the electrical conductivity, surface wettability, surface roughness, and electrochemical reactivity of the IML PG. Finally, we demonstrate how a newer variant of nano/microstructured PG called laser induced graphene (LIG) can be fabricated. This graphene fabrication technique utilizes a scalable direct-write laser fabrication process that converts polyimide into LIG which eliminates the need for chemical synthesis of graphene, ink formulation, masks, stencils, pattern rolls, and post-print annealing commonly associated with other PG sensors.

Finally, we demonstrate how these graphene-based circuits can be biofunctionalized with enzymes [phosphotriesterase (PTE) and acetylcholinesterase (AChE)] for organophosphate sensing or ion selective membranes for ammonium, nitrate, and potassium sensing in river water soil slurry, or urine samples. The PTE and AChE enzymes offer distinct sensing paradigms where PTE is activated by organophosphates and AChE is inhibited. The detection limits of the biosensors so far have achieved approximately 0.6 nM for organophosphate pesticides which well below the concentration limits we would expect for drinking water or soil samples. We also demonstrate how LIG electrodes were capable of monitoring four major neonicotinoids (CLO, IMD, TMX, and DNT) with low detection limits (CLO - 823 nM; IMD - 384 nM; TMX - 338 nM; and DNT - 682 nM) and a rapid response time (~10s) using square wave voltammetry without chemical/biological functionalization. Finally, we demonstrate how the surface wettability of the LIG can be tuned in order to create narrowing, wedge-shaped hydrophilic tracks surrounded by superhydrophobic walls that permit movement of fluid along the tracks by net Laplace pressure (i.e., open microfluidics). Such definitive control over material properties enables the creation of LIG-based integrated open microfluidics and electrochemical sensors that are capable of splitting a single water sample along four multifurcating paths to three ion selective electrodes (ISEs) for potassium (K⁺), nitrate (NO₃^-), and ammonium (NH₄⁺) monitoring and to an enzymatic pesticide sensor for organophosphate pesticide (parathion) monitoring. The ISEs displayed near-Nernstian sensitivities and low limits of detection (LODs) (10^-5.01 M, 10^-5.07 M, and 10^-4.89 M for the K⁺, NO₃^-, and NH₄⁺ ISEs, respectively) while the pesticide sensor exhibited the lowest LOD (15.4 pM) for an electrochemical parathion sensor to date. Hence, this unique and tunable fabrication approach to PG is expected to enable a wide range of real-time, point-of-use health and environmental sensors.

Continuously emerging antimicrobial resistance (AMR) in bacteria is a global challenge. Herein, we propose the strategy to utilize bactericidal multimetallic ternary (Fe/Ni/Cu) nanoparticles (NPs) to address the rising AMR challenge. The ternary NPs were synthesized by using aerosol mediated nebulized spray pyrolysis method. The pure metallic FCC crystal structure of NPs was confirmed by using atomic resolution high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) analysis. Further energy dispersive X-ray spectroscopy (STEM-EDS) technique was used to confirm the elemental composition of synthesized NPs. In-situ graphene liquid cell (GLC) STEM novel approach was utilized to investigate the antibacterial mechanisms of action of these ternary NPs against Escherichia Coli (E. Coli) bacteria. Cryo-electron microscopy and conventional transmission electron microscopy (TEM) coupled with ultramicrotomy are well-studied and widely utilized approaches to investigate the antibacterial mechanisms of actions of bactericidal nanomaterials. Although these approaches have shown potential to evaluate the nanoscale antibacterial mechanisms, there exists challenges with lower spatial resolution and the tedious steps involved for the sample preparation. In-situ GLC STEM approach allows faster sample preparation with minimal efforts and can provide insights of dynamic nanoscale events of antibacterial mechanisms of action. Moreover, GLC has unique advantages with higher spatial resolution and capability to reduce the electron beam damage, especially for the soft matter. In the present study, graphene coated TEM gold grids were prepared by transferring chemical vapor deposition (CVD) grown graphene upon etching of the copper substrate. To prepare GLC pockets, 0.3 µL of reaction solution was encapsulated between two graphene coated TEM grids. E. Coli bacteria were cultured prior to the experiments in the LB broth culture media for 4 hours under 37^oC incubation. For in-situ GLC experiments, the final concentration of cultured E. Coli bacteria was as low as 20 CFU/ml. To acquire better contrast during STEM study and to reduce the organic content in the cell media, cultured bacteria were transferred into the ultrapure water for GLC studies. For investigating the antibacterial mechanisms of ternary NPs, NPs with 25 µg/ml concentration were mixed with cultured E. Coli bacteria in water medium. Upon 10 minutes of interaction, the NPs treated bacteria were immediately encapsulated between TEM grids for GLC studies. STEM-imaging and STEM-EDS mapping acquired in GLC clearly indicate the presence of nitrogen (N), oxygen (O), carbon (C), chlorine (Cl) and phosphorus (P) diagnostic ions, mapping the bacterium morphology and cellular integrity. Cl is responsible for the osmotic balance in the bacterium, while N is associated with amino acids. P is present in the phosphorylated proteins and deoxyribonucleic acid, while O and C are present in almost all cellular components. The cellular integrity of control bacterium was disrupted upon treating with ternary NPs for 10 minutes. Fe, Ni, and Cu metal ions were observed inside the bacterium cytoplasm and along the cell wall, confirming the synergistic release of metal ions. Results also confirm that the ions release rate from the ternary NPs follows a trend, as Cu ions > Ni ions > Fe ions. Further organic corona formed around the NPs was investigated to be the bacterium cytoplasmic and cell membrane components. Synergistic and varying rate of (Fe/Ni/Cu) ions release from the ternary NPs can inactivate the bacteria without allowing to develop AMR and can provide prolonged bactericidal efficiency. The present work investigates the real time nanoscale mechanisms of antibacterial activity of multimetallic NPs, encouraging the developments of novel drug delivery strategies.

Sequencing the human genome has helped to improve our understanding of disease, inheritance and individuality. Solid-state nanopores could potentially meet the demand for even cheaper and faster genome sequencing, owing to their superior mechanical, chemical and thermal robustness and durability, and potential for integration into high-density electronic arrays.¹ Despite the promise, solid state nanopores have yet to demonstrate DNA sequencing. Two key challenges remain, i.e., achieving few-base spatial resolution and slowing the translocation of the DNA molecule. 2D materials such as graphene² and MoS₂³ have emerged as attractive possibilities, since the thickness of these films is in the range of a few nucleotides. However, atomic membranes alone are not robust in fluid under an electric field.⁴ 2D materials sandwiched within dielectrics could provide a stable platform,⁵ but the resulting stack thickness limits the spatial resolution. Resolving these challenges requires new sensing mechanisms beyond ionic currents and translocation control.
This work reports a novel solid state nanopore sensor that has the desired spatial resolution of sub nanometer, integrated electrical sensing, and can potentially control the translocation of the DNA molecule. In this architecture, the nanopore is drilled through a vertical 2D heterostructure consisting of n-type MoS₂ and p-type WSe₂. The heterostructure forms an atomically thin out-of-plane p-n diode. The diode is passivated by atomic layer deposition (ALD) of HfO₂ for electrical insulation. We validated the robustness of the 2D heterostructure nanopore architecture with ionic sensing, by acquiring thousands of DNA translocation events under three different ionic biases. Then we demonstrated modulation of ionic current by 2D diode interlayer potential. Ionic current modulation is more effective with smaller pores and lower salt concentrations, and thus is not caused by leakage or edge electrochemistry. Modulation of ionic transport is also more effective under forward bias than under reverse bias, as a larger fraction of in-plane bias drops across the vertical p-n junction under forward bias.⁶ Finally, we obtained signatures of DNA translocation in ionic and diode channels simultaneously. DNA translocation in 10 mM KCl resulted in current increase in ionic channel, as well as current increase in diode channel. The diode channel had better signal-to-noise ratio than the ionic channel. To our knowledge, these proof-of-principle experiments are first-of-its-kind demonstration of 1) simultaneous detection of DNA translocation in a 2D diode nanopore device in both ionic and electrical channels, and 2) modulation of ionic current by the interlayer potential of 2D diode.

References:
(1) Lindsay, S. The Promises and Challenges of Solid-State Sequencing. Nat. Nanotechnol. 2016, 11 (2), 109–111.
(2) Garaj, S.; Hubbard, W.; Reina, A.; Kong, J.; Branton, D.; Golovchenko, J. A. Graphene as a Subnanometre Trans-Electrode Membrane. Nature 2010, 467 (7312), 190–193.
(3) Feng, J.; Liu, K.; Bulushev, R. D.; Khlybov, S.; Dumcenco, D.; Kis, A.; Radenovic, A. Identification of Single Nucleotides in MoS₂ Nanopores. Nat. Nanotechnol. 2015, 10 (12), 1070–1076.
(4) Graf, M.; Lihter, M.; Thakur, M.; Georgiou, V.; Topolancik, J.; Ilic, B. R.; Liu, K.; Feng, J.; Astier, Y.; Radenovic, A. Fabrication and Practical Applications of Molybdenum Disulfide Nanopores. Nat. Protoc. 2019, 14 (4), 1130–1168.
(5) Venkatesan, B. M.; Estrada, D.; Banerjee, S.; Jin, X.; Dorgan, V. E.; Bae, M. H.; Aluru, N. R.; Pop, E.; Bashir, R. Stacked Graphene-Al₂O₃ Nanopore Sensors for Sensitive Detection of DNA and DNA-Protein Complexes. ACS Nano 2012, 6 (1), 441–450.
(6) Lee, C. H.; Lee, G. H.; Van Der Zande, A. M.; Chen, W.; Li, Y.; Han, M.; Cui, X.; Arefe, G.; Nuckolls, C.; Heinz, T. F.; et al. Atomically Thin P-n Junctions with van Der Waals Heterointerfaces. Nat. Nanotechnol. 2014, 9 (9), 676–681.

This paper describes the use of graphene-based sensors for the real-time detection of physiologically-relevant ions and volatile organic compounds (VOCs). Specifically, we have developed a robust sensing platform with more than 200 sensing units on a transparent glass substrate connected to a custom hand-held readout circuit. This system is then combined with a novel calibration algorithm and machine learning software to provide excellent reproducibility and accuracy over a wide range of physiologically-relevant analytes. For example, using this system, potassium, sodium and calcium ions have been detected and their relative concentrations have been identified in complex multi-ion electrolytes. An analytical study of the impact of sensor redundancy on the sensitivity and reproducibility of the sensing platform will be presented. The impact of device calibration and machine learning data analysis on system performance will also be discussed. Finally, the use of the graphene sensing platform for the detection of VOC’s in both breath and skin will be described, as well as the potential of this technology for diagnosis of different disease.

Stemming the exponential growth of emergent infectious disease (e.g., COVID-19) requires prompt detection of infection followed by isolation and treatment of the afflicted. If unchecked, infectious evolutionary events can upend the fundamental institutions constituting Homo sapiens' society and economy. Here, a biosensing platform is realized via surface functionalization of a two-dimensional channel comprised of graphene/hexagonal boron nitride (hBN) heterostructure field-effect transistor with monoclonal immunoglobulin G specific for SARS-CoV-2 antigen protein. Several surface functionalization schemes with real-time monitoring of surface modification and sensation on both G- and hBN/G-FETs have been performed. These low-cost devices have been observed to be ultra-sensitive to ≥200 ag/mL SARS-CoV-2 spike protein S1 subunit in 1X phosphate buffered saline. This is ~1-3 orders of magnitude lower than contemporary molecular diagnostics (i.e., RT-PCR and ELISA, respectively). Graphene and hBN/graphene materials and fabrication process are characterized with Raman spectroscopy, X-ray reflectometry, atomic force microscopy, and biosensor performance evaluated with two- and three-terminal electrical measurements. The G- and hBN/G-FET devices used in this study contribute to the growing body of knowledge regarding graphene applications in biosensing by including a passivating hexagonal boron nitride layer and help pave the path toward lab-on-chip platforms for point-of-care applications.

Graphene-related materials (GRM) such as graphene oxide (GO) and graphene quantum dots (GQDs) display advantageous characteristics with interest for building innovative biosensing platforms and even smart devices such as nano/micromotors for a myriad of uses including sensing. Quenching of the fluorescence induced by GO or photoluminescence of GQDs can easily operate in synergy with various other nanomaterials and platforms opening the way to several unprecedented biosensing strategies and unique nanomotor technologies. Taking advantage of GRMs we are developing simple, sensitive, selective and rapid biosensing platforms that include: a) GO – based microarray & laterals flow technologies taking advantages of high quenching efficiency of GO. A “turn ON by a pathogen” device will be shown as a highly sensitive detection system using plastics or paper/nanopaper substrates; b) GQDs–based sensors for contaminants detection based on the use of multifunctional composite materials that enable rapid, simple and sensitive platforms in connection to smartphone; c) electroluminescent-based approaches d) A water activated GO transfer technology using wax printed membranes for fast patterning of a touch sensitive device with interest for electronic devices including sensing as well as for a cost-efficient nanomotor building technology for several applications. This work is supported by EU (Graphene Flagship), CERCA Programme / Generalitat de Catalunya.

Mental stress negatively impacts more than 77% population in our modern societies. Electrodermal activity (EDA), a.k.a. galvanic skin response (GSR), is an emotion-induced skin conductance change due to sweat gland activity, which has been widely used as a quantitative index of mental stress levels for decades. Palm has the highest density of eccrine sweat glands which are filled up under psychological stimuli, such as mental stress, primarily. However, state-of-the-art EDA monitors suffer from limitations such as obstructiveness, short-term wearability, motion artifacts, etc. My group has previously engineered mechanically and optically imperceptible wearable sensors named graphene e-tattoos (GET).[1-3] Herein, we introduce a wireless, long-term wearable (e.g. 24 hours), high-fidelity palm EDA sensor based on 150-nm-thick GET. The ultrathin GET can fully conform to the finest texture of human skin, resulting in an interface impedance even lower than that of the wet Ag/AgCl gel electrodes. GET is laminated on the palm and needs to extend to the wrist to connect to a wristwatch which provides data acquisition, storage, and wireless transmission. The orders-of-magnitude mismatch of stiffness and thickness between the GET and the wristwatch poses a significant challenge for the electrical connection in between. We propose a simple yet effective solution named “heterogenous serpentine ribbon (HSR).” Compared with contacts between straight GET and metal ribbons, HSR offers a ten-fold strain reduction. We have successfully applied such GET-watch-based wearable EDA sensor for long-term, continuous, and ambulatory EDA sensing during our daily activities as well as during sleep. The HSR could be a generic solution to robustly connect any ultrathin and ultrasoft e-tattoos to smartwatches or rigid PCBs, which could significantly expand the sensing modalities of future smartwatches and other wearable devices.

1 Ameri, S.K., Ho, R., Jang, H.W., Tao, L., Wang, Y.H., Wang, L., Schnyer, D.M., Akinwande, D., and Lu, N.: ‘Graphene Electronic Tattoo Sensors’, Acs Nano, 2017, 11, (8), pp. 7634-7641
2 Ameri, S.K., Kim, M., Kuang, I.A., Perera, W.K., Alshiekh, M., Jeong, H., Topcu, U., Akinwande, D., and Lu, N.: ‘Imperceptible Electrooculography Graphene Sensor System for Human-Robot Interface ’, npj 2D Materials and Applications, 2018, 2, pp. 19
3 Kireev, D., Ameri, S.K., Nederveld, A., Kampfe, J., Jang, H., Lu, N., and Akinwande, D.: ‘Fabrication, characterization and applications of graphene electronic tattoos’, Nature Protocols, 2021, 16, (5), pp. 2395-2417

The miniaturized image sensor has received great attention recently, due to their significances in micro-robotics. Current research mainly focuses on developing curved image sensors to correct the field curvature induced by the small lens. However, the innovations in color image sensors are so far very rare, because of the two major challenges. First, conventional image sensors typically adopt a Bayer filter to endow the laterally arranged pixel with the function of color sensing, rendering a large device profile. Second, aggravated optical chromatic aberrations due to lens system simplification is another difficulty. In this study, we developed a novel vertical color recognition structure (CRS) by stacking multiple layers of van der Waals semiconductors (vdW-S) including CuIn₇Se₁₁, InSe, and GaS as the sensing layers which are sensitive to red, green, and blue light from bottom to top, and the neighboring sensing layers are separated with flexible and transparent insulating materials, such as mica or hexagonal boron nitride to prevent short circuits. Meanwhile, adjusting the thickness of these insulating layers makes it feasible to align each of the sensing layers to their respective focal plan to compensate the chromatic aberration. Experimentally, upon the successful fabrication of the CRS, by carefully selecting the vdW-S and control their thicknesses, each sensing layer obtained the desired spectral responses, as well as excellent photoresponsivity linearly depending on incident light power. In addition, depending on the structural superiority of the vertical stacking design, the simulation of chromatic aberration correction based on this CRS is also achieved. The as-developed CRS can serve as individual pixels and implement miniaturized full color image sensor through a scalable fabrication and integration of them, with incomparable advantages in a compact size, aberration correction function for the utilization in medical care, environmental surveillance, and many other areas.

Colloidal particles with 2-dimensional geometry exhibit high adhesion energy at the interface so there have been studied to synthesized new types of particles with a tailored platelet structure. Compared to typical spherical particles, high aspect ratio of 2D nanoparticles not only stabilize interface more effective but also enhance the interaction between particles due to their large lateral surface area. A platform is introduced for bilayered coacervation of oppositely charged nanoplatelets (NPLs) at the oil-water interface. To this end, we synthesized two types of zirconium hydrogen phosphate (ZrHP) NPLs, cationically charged NPLs (CNPLs), and anionically charged NPLs (ANPLs) by conducting surface-initiated atom transfer radical polymerization. Taking advantages of the platelet geometry and controlled wettability, we demonstrated that ANPLs and CNPLs coacervate themselves to form a bilayered NPL membrane at the interface, which was directly confirmed by confocal laser scanning microscopy. Via theoretical consideration using the hit-and miss Monte Carlo method, we determined that electrostatic attraction-driven coacervation of ANPLs and CNPLs at the interface shows a minimum attachment energy of ~-10⁶ k_bT, which is comparable to the cases where NPLs charged with the same type of ions are attached. This unique and novel interfacial coacervation behavior allowed use to develop a pH-responsive smart Pickering emulsion system. All of these results highlight that platelet-type colloids are indeed effective in inducing controllable interfacial adsorption and desorption at interfaces, as well as interactions between them, and also pave ways to develop various interfacial engineering technologies.

A synergistic, nanoscale electrical interface with the membranes of exoelectrogenic microbes will have a transformative impact on biological cell-based electronic devices. Here, we report that a conformal graphenic interface on biocatalytic Geobacter sulfurreducens membrane results in quantum-capacitance induced n-doping in reduced graphene oxide (rGO) that further enhances electron shuttling from the membrane to improve electron harvesting from the electrogenic organism. The quantum coupling of rGO with the connected protein-membrane channels leads to an additional electron density of 3.91 x 10¹²cm^-2 and an increase in the in-plane phonon vibration energies (G) of rGO by ~5 cm^-1. This n-doping enhances the electron transfer rate from the cell membrane into the rGO via a net driving potential of 158 meV with a 3-fold increase in the power density. The synergistic electron-harvesting and conformal membrane-interfacing of flexible 2D nanomaterials can lead to an evolution in the design of microbe-circuitry to power stand-alone nanodevices.

To leverage recent advances in the production of printed graphene electrodes, there exists a need to develop a graphene ink suitable for high-throughput fabrication processes. Herein, we fine-tune previously developed graphene ink, formulated with exfoliated graphene and an ethyl cellulose stabilizing polymer, to be suitable for flexographic printing. Further, the impact of process parameters and ink formulation are investigated by analyzing print quality and electrical properties. Characterization reveals anisotropic electrical properties due to striations caused by viscous fingering. Ambient environmental responses are characterized, which inform the scope of graphene electrode applications and need for functionalization of graphene in complex environments. Overall, this work informs the viability of graphene as an environmental and biological sensor and outlines fabrication constraints of production scale printed graphene electrodes.

The advent of pandemic caused by SARS-CoV-2 (COVID-19) has highlighted the requirement of devices capable of carrying out rapid differential diagnosis of various viruses that may manifest similar physiological symptoms but demand tailored treatment plan. Annually, the world undergoes multiple cycles of seasonal Flu infection which now poses a bigger challenge, exacerbated by the pandemic. In this work, we demonstrate liquid-gated graphene field effect transistor (GFET) based rapid biosensing device capable of making differential diagnosis between Influenza (H3N2) and COVID-19 viruses. The device consists of four onboard GFETs arranged in a quadruple architecture, where each quarter is functionalized with specific antibody to utilize the antibody-antigen reaction on graphene’s surface to indicate the presence of either Influenza (H3N2) or COVID-19. The antigen-antibody interaction is dependent on uniform diffusion of virus delivered in low ionic strength phosphate buffered saline, entailing a facile operating procedure, where the user is only required to pipette in a drop of the viral solution onto the device.
Our devices were sucessfully tested against a range of concentrations of both the viruses (COVID-19 and Influenza), indicating extremely high sensitivity. Unlike the standard polymerase chain reaction-based testing kits which have a turn-around time of at least three hours, our device has a lower response time of a few milliseconds; hence enabling rapid diagnosis. Furthermore, the device is highly specific as confirmed by cross-reactivity tests: the COVID-19 functionalized channels are not reactive to the Influenza virus, and the Influenza-functionalized channels are not reactive to the COVID-19 spike protein. In addition, both the channels are not reactive to the introduction of bovine serum albumin, confirming excellent specificity of the multi-targeted biosensor.

Over the past two decades, graphene has attracted a great deal of attention due to its extraordinary properties. When these properties are translated into applications graphene could have a large impact in various industries and markets such as telecommunications, healthcare, automotive, etc. However, for this to occur there are many milestones that have to be achieved such as graphene manufacturing (growth and transfer) and device fabrication at relevant wafer scales, before moving to component fabrication and system integration into the final product.

Graphene’s electronic and mechanical properties make it an ideal candidate to be applied in various types of sensors. The sensors’ market is extremely large since we are dealing with the automotive, electronics and healthcare industries among others. Therefore, it is an excellent starting platform for graphene applications. For example, the current COVID-19 pandemic has demonstrated the urgent need for fast diagnostics in order to minimise and control its effects, here, biosensors based on graphene field effect transistors (GFETs) have shown great potential as a platform for future diagnostics.

During this talk, I will cover the fabrication of graphene at wafer scale and the use of graphene in various types of sensors including MEMS [1,2], ion sensors (ISFETs) [3-5], gas sensors [6] and biosensors. Depending on the type of sensor, the graphene requirements including the transfer and characterisation vary considerably.



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C. Mackin, V. Schroeder, A. Zurutuza, C. Su, J. Kong, T.M. Swager and T. Palacios, ACS Appl. Mater. Inter., 10 (2018) 16169.

Large effort is being dedicated to the integration of novel materials into neural interface devices capable of providing an efficient and consistent activity for the duration of their functional lifetime. Recording capabilities need to be such that they allow the detection of brain activity over large areas and with a high spatial resolution. For stimulation applications, a suitable charge injection capacity is required in order to elicit a response from the tissue being targeted without causing damage. Additionally, these devices must be biocompatible and mechanically compliant with neural tissue. Because its two-dimensional nature, graphene exhibits a rather unique combination of physicochemical properties which make it an attractive platform for neural technologies.
This contribution will focus on the recording capabilities of active sensor technology based on single-layer graphene, highlighting its potential for the development of the next-generation neural prostheses and brain-computer interfaces. Recently, solution-gated field-effect transistors (SGFET) based on graphene are being explored with increasing interest as novel transducers for neural signals. The electrochemical stability of graphene and its facile integration with flexible substrates were among the initial triggers that attracted the interest of the community to develop flexible neural probes for brain interfacing. In addition, other properties such as the high carrier mobility and the field effect associated to single-layer graphene allows for the implementation of an active sensor configuration that will be shown in this contribution to offer significant advantages with respect to the classical passive metallic electrodes. Further, this presentation will discuss how SGFET-type sensors allow us the implementation of multiplexing strategies, time-domain and frequency-domain multiplexing, that reduce the footprint of connectivity, permitting an aggressive scaling up in the number of recording sites. Very interestingly, we will demonstrate that SGFETs also have a distinctive capability to expand the temporal resolution of classical electrocorticography technologies, allowing the recording of the relatively unexplored infra-slow brain activity and, thus, potentially enabling the study of novel biomarkers for monitoring neurological disorders.
Acknowledgements. This work has been partially funded by the EU Horizon 2020 programme under Grant Agreement no. 881603 (GrapheneCore3) and no. 732032 (BrainCom)

The complexity of neural activities has challenged both neuroscience research and clinical practice for decades. Understanding neuronal dynamics and information processing performed by neural populations requires advanced technologies with high-resolution sensing and stimulation capability. Clinical neuromodulation therapies widely used for neurological disorders also depend on the ability to manipulate the dynamics of neural circuits. Conventional neural interfaces offering electrical, optical, or chemical signals have greatly advanced our understanding of neural functions, however, most of these technologies are based on a single functionality. Combining multiple functionalities in a single system has recently been pursued as an integrative approach in new neurotechnology development. Graphene has recently emerged as a neural interface material offering several outstanding properties, such as optical transparency, flexibility, high conductivity, functionalization and biocompatibility. The unique combination of these properties in a single material system makes graphene an attractive choice for multi-modal probing of neural activity. In this talk, I will present our recent work on graphene-based neural interfaces, highlight key applications, and finally discuss future directions and potential advances for graphene-based neurotechnologies in both basic neuroscience research and medical applications.

Due to the development of various advanced new materials and process technologies, electronic devices are being reduced in size to a microscale and are being integrated with high density in a limited area. Through this, energy is saved and performance and efficiency are greatly improved, but heat generated from components of device concentrated in a narrow area is a new problem that cannot be found in previous conventional devices. In particular, in the case of the micro light emitting diodes (LEDs), the heat problem more stands out as it is used as densely integrated injectable or wearable devices for photodynamic therapy, optogenetics, and various sensors. The heat generated by the LED causes problems such as deterioration of light emitting performance, change of emission wavelength property, and reduction of lifespan, which can be a fatal disadvantage to the device.
Although in order to solve this problem, recent research tried to control the LEDs temperature through various methods such as size reduction, pulsed operation, and high thermal conductivity substrate, these are acceptable in limited applications, and it is difficult to apply on the bio-injectable devices.
Here, we present an injectable neural opto-probe using the Boron Nitride (BN) as a heat dissipation layer. BN is a 2D inorganic material with excellent thermal stability, electrical inlsulation property, and high thermal conductivity. Recently, various research using it as a heat dissipation material have been published. We applied the BN to neural opto-probe device as a heat dissipation layer to effectively disperse the heat generated during operation. The temperature of the device is verified through finite element method simulation and actual IR temperature measurement to ensure heat dissipation performance of up to 40°C or higher. This heat dissipation performance increased the thermal stability of the device, thereby increase the emitting efficiency of the LEDs and preventing the red shift of the wavelength of the LEDs by spreading the heat from the heat source. The heat dissipation neural opto-probe has superior emitting performance than general devices, and the penetration depth of light in vivo, especially in the brain, has been greatly increased. Through this, it was possible to develop a device that can effectively deliver light to a wider range in applications such as PDT and optogenetics.

In decades, neural interfacing devices have attracted huge attention because they can provide not only diagnosis of neurodegenerative diseases but also treatment for a patient suffering from them. Recent researches on surface neural electrodes on the cortical surface have suggested that recording ECoG can diagnose neurodegenerative diseases and also treat them with electrical stimulation. In order to achieve the chemically stable, biocompatible, and electrochemically conductive neural interface, various materials have been investigated such as noble metals, conductive polymers, and nanomaterials. However, each of them has still several defects such as non-transparency, unstability in long-term implantation, their mechanically stiff nature, which impede the chronic biomedical use of implantable devices. Graphene is one of the nanoscale forms of carbon materials, which consists of a single-atomic hexagonal lattice of sp² hybridized carbon atoms. It is an attractive candidate for implantable biomedical devices due to its excellent electrochemical property, biocompatibility, chemically inert nature, and mechanically flexibility.
Herein, we suggest graphene-based neural electrode arrays for the treatment of epilepsy. We investigated various graphene-based electrodes for improving the neural interface. First is 4-layer doped graphene. The second one is graphene/Au/graphene sandwich structure. The sandwich structure was synthesized with the followed process; (1) conventional CVD growth process of graphene on copper foil (2) deposition of nanoscale thick gold layer on it (3) wet transfer of monolayer graphene coated with PMMA on it. The sandwich structure takes both advantages of electrical conductivity of gold and electrochemical property and a good interface with neural cells of graphene. We electrochemically characterized these graphene-based electrode arrays and long-term stability and biocompatibility after in-vivo implantation. Finally, we successfully demonstrated detection of epileptic form neural activity and treatment of epilepsy using electrical stimulation in-vivo rat experiments. These graphene-based electrodes showed very high signal-noise-ratio compared with other neural electrodes and the capability to treat brain diseases. We expect that our graphene-based electrode arrays can demonstrate a breakthrough toward the non-invasive medical application of neural devices.

Sensors for ubiquitous sensing purposes should be low-cost, invisible and seamlessly integrable with many different surfaces such as bendable plastic, textiles and glass. Graphene based light sensors [1,2] are inherently flexible and transparent and can be integrated with low-cost CMOS technology [3], hence providing a disruptive platform for future wearables and vision devices.
We will show a prototype non-invasive wellness monitor based on hybrid nanoparticle-2D material systems. We leveraged graphene’s flexible and transparent properties to create a wearable device that is conformal to the human body so that it can reliably extract vital signs such as heart rate, breathing rate and oxygen saturation [4]. Furthermore, we present a graphene-based UV-sensing patch. It records harmful UV-exposure on the skin. The patch does not need a battery as a smartphone provides energy via wireless power transfer.

Moreover, we present the first transparent camera based on an array of graphene photodetectors. These transparent image sensors can have a far-reaching impact on human-computer interfaces, smart displays, and eye-tracking for augmented and virtual reality. The operation of these devices presents a fundamental shift in how we think about image sensor, as these devices can be hidden in plain sight.


References
[1] G. Konstantatos, et al., Nature Nanotechnol., 7 (2012)
[2] Nikitskiy et al., Nat. Commun., 7 (2016)
[3] Goossens et al., Nat. Phot. 11 (2017)
[4] Polat et al., Science Advances (2019)

Graphene materials are emerging systems for wearable electronics and smart textiles applications due to their exceptional properties such as electrical conductivity, optical transparency and mechanical flexibility. These properties offer opportunities for the seamless incorporation of electronic devices in textiles, unlocking a future where interacting with bio-electronic devices will be as simple as getting dressed. In this invited talk, I will give an overview of our developments in the integration of graphene materials with flexible substrates, including textile fibers and fabrics for various wearable applications.
In our earlier studies [Sci. Rep. 5, 9866 (2015) and Sci. Rep.7, 4250 (2017)] we demonstrated a versatile method to coat a wide range of common insulating textile fibres with monolayer and few layer graphene grown by Chemical Vapor Deposition. Fibre materials such as polypropylene, polylactic acid, polyethylene and nylon, of tape and cylindrical shapes, display sheet resistance values as low as 600 Ohm/ sq, demonstrating that the high conductivity of graphene is not lost when transferred to textile fibres. These graphene-based conductive fibres were used as a platform to build integrated electronic devices directly in textiles. For example, we demonstrated graphene electronic textile fibers that function as touch-sensors and light-emitting devices [npj Flexible Electronics 2, 25 (2018)]. We also demonstrated the weaving of such graphene electronic fibres in a fabric which enabled the realization of pixels for displays and position sensitive functions. Finally, we recently demonstrated the use of graphene-coated polypropylene (PP) textile fibers as temperature sensors within a low-operating voltage carbon–graphene e-textile system [ACS Appl. Mater. Interfaces 12, 26, 29861 (2020)].
For the development of fabric-based wearable devices, one of the critical challenges is the seamless incorporation of electronics in textiles that will preserve their softness and comfort. A key feature is the realisation of electrically conductive coatings on textile that conform to the irregular and coarse structures of the textile fabrics. Therefore, a different approach compared to fibers is needed for creating conductive textile fabrics without compromising the properties of the fabric. We recently demonstrated a simple, low-cost, efficient, and highly scalable method of ultrasonic spray coating for coating three types of textile fabrics, meta-aramid, polyester and nylon, with a water based graphene nanoplatelets suspension [J. Phys. Mater. 4 014004 (2021)]. These conductive textile fabric electrodes show a sheet resistance as low as 4.5 kOhm/sq without any intentional doping or required additives for improved adhesion. Such fabric electrodes have applications in sensors or energy-harvesting wearable technologies.
One of the main advantages of 2D materials for various applications is that they can be prepared in form of water-based solutions. The high yield and cost-effectiveness of this method make them of great interest for printed electronics, composites, and bio- and healthcare technologies. In the final part of my talk I will discuss our developments in this area. I will present the integration of high quality graphene films obtained from scalable water processing approaches in emerging energy harvesting devices [Adv. Mater. 30, 1802953 (2018)], opening new possibilities for self-powered electronic skin, flexible and wearable electronics. Building on this work, we developed a method for the fabrication of micrometer-sized well-defined patterns in water-based 2D materials [Adv. Sci. 6, 1802318 (2019)]. This method was used to create humidity sensors with performance comparable to that of commercial ones. These sensor devices are fabricated onto a 4 inch polyethylene terephthalate (PET) wafers to create all-graphene humidity sensors that are flexible, transparent, and compatible with current roll-to-roll workflow.

Laser-based modification of polymers has been emerging as a versatile method to simultaneously synthesize and pattern electrically conductive structures on polymer substrates for flexible device applications. By simply irradiating and scanning the polymer substrate with a laser beam, optical and thermal effects are induced near the focal spot, and electrically conductive graphitic carbon (ie., laser-induced graphene, LIG) can be directly patterned onto the substrate. Although laser modification is promising for the fabrication of flexible devices, polymer precursors used in previous studies are limited to inelastic materials, such as polyimide (PI) and biomasses (ie., cellulose). We have been studying the femtosecond laser-induced graphitization of a well-known elastomer, polydimethylsiloxane (PDMS). PDMS-based LIG generally shows comparably lower conductivity than those of structures fabricated from PI, possibly due to the aliphatic structure of PDMS, hindering graphitization. However, fabrication of highly conductive structures, composed of highly-crystalline graphene, was achieved by irradiating femtosecond laser pulses at a high repetition rate onto the surface of native PDMS. The structures fabricated by using our method exhibited an electrical conductivity as high as ~51.6 S m^-1, which is, to the best of our knowledge, the highest value achieved (ie., ~300% of highest value previously reported) using the laser modification of PDMS. Raman analyses of the fabricated structures indicated the formation of highly crystalline and few-layered graphene by laser irradiation, which is considered to contribute to the high conductivity of the fabricated structures. Furthermore, when the fabricated structures were excited using UV light (365 nm), photoluminescence was observed for the fabricated structures. The emission spectra obtained from the structures indicated two peaks centered at 400 nm and 720 nm, suggesting the formation of nano-sized carbonaceous (ie., carbon quantum dots, graphene quantum dots) and siliconaceous (ie., silicon carbide, porous silicon) structures, respectively. The structures fabricated with the proposed method exhibited piezoresistive behavior, and by exploiting the elasticity of PDMS, in combination with the high conductivity of the fabricated structures, a soft, small, and sensitive (ie., ~2.2 kPa^-1) piezoresistive sensor that could detect pressures as low as approximately 0.1 Pa was realized. When compression cycle tests were performed on the sensors, the relative changes in resistance to applied pressure at the end of compression cycles were comparable to those at the beginning, indicating high stability and repeatability. The high sensitivity indicated by the sensor, regardless of the small size, is attributable to the elasticity of the PDMS substrate. Furthermore, a PDMS-based ring-shaped heartrate (HR) monitor capable of obtaining the pulse wave-form, and resultantly the HR, of the human subject from just the index finger was demonstrated; indicating the potential of the structures fabricated with the proposed method for health monitoring applications.

COVID-19 was one of the leading causes of death in the United States in 2020 and early 2021 and it continues to threaten public health. Thus, it is imperative to understand and identify SARS-CoV-2 including different mutant lineages. Surface-enhanced Raman spectroscopy (SERS) can provide characteristic fingerprints of biomolecules, and with the assistance of machine learning, can become a powerful tool to rapidly identify and understand complicated biosamples. In this work, we developed a platform combining SERS and machine learning to detect the receptor-binding domain (RBD) of SARS-CoV-2 spike protein, a key component related to the infection and transmission. The Raman modes of SARS-CoV-2 RBD were enhanced by gold nanoparticles under a 785 nm laser. To understand the origin of the Raman modes, we analyzed the correlation between the Raman spectra of SARS-CoV-2 RBD and compositing amino acids using our Frequency Matching algorithm and achieved high consistency with the genome sequence. In addition, we can classify RBDs of SARS-CoV-2 and MERS-CoV with accuracy, precision, and recall all over 97% using machine learning classifiers. Our SERS-machine learning integrated platform holds promise for rapid detection of SARS-CoV-2 mutants that hinder the immunity efficacy.

In recent years, graphene and its derivatives have been demonstrated as valuable materials for the development of several kind of biochemical sensors. In particular, its integration in Field-Effect Transistor (FET) structures as active layer has been thoroughly explored in literature. Nonetheless, graphene-based FETs are typically characterized by poor switching properties, which severely limit their actual exploitation in electronic circuits. Moreover, proposed devices typically need a reference electrode in the measurement environment, which is another important limitation for their actual exploitation in a real application scenario.
Here, we report an innovative approach, using graphene as conductive element in a peculiar device structure named Organic Charge-Modulated FET (OCMFET). The OCMFET is a floating gate Organic FET, where a part of the floating gate, namely the sensing area, is exposed to the measurement environment. Through a modification of the sensing area with a proper biochemical receptor, the floating gate can act as a probe for the investigated analytes, which is recognized by means charge variations/modulations induced in the measurement environment and then transduced in a variation of the threshold voltage of the transistor. By decoupling the sensing element by the active layer of the transistor, it is possible to exploit at their best the peculiar properties of graphene as sensing element, while the transistor structure can be optimized to reach electronic performances suitable for the future integration into electronic systems. Moreover, the OCMFET operates in a electrically-floating environment, i.e. the need for a reference electrode in solution is avoided.

It is noteworthy that, although the OCMFET working principle has been already successfully exploited in several kinds of biochemical sensors, conventional materials and fabrication processes have been always employed, as well as chemical functionalization processes of the sensing area. In this new version of the OCMFET, graphene is used for defining the floating gate and the sensing area of the OCMFET, while the other elements in the transistor structure are defined by means of large area, industrial-like techniques such as Chemical Vapor Deposition and inkjet printing. Moreover, we report a straightforward, non-convalent modification of graphene by means of molecules hosting a pyrene moiety, which ensures an highly stable functionalization without affecting the optical and electrical properties of graphene.

As a result, the fabrication process here proposed is suitable for future scale-up to an industrial scale. Taking advantage of the peculiar optical properties of graphene and of the organic materials employed for the fabrication of the transistor structure, highly transparent devices have been fabricated, showing a transmittance higher than 90%.

The actual functionality of this new OCMFET implementation as biochemical sensor has been demonstrated considering pH sensing as a benchmark. Graphene has been non-covalently functionalized with pyrenate peptides hosting chemical groups that can change their charge state with pH. A complete characterization in a wide pH range (3-12) has been carried out using peptides with different net charge profiles. This study paves the way to the development of novel, high-performing sensors integrating graphene and organic semiconductor-based devices.

Graphene biosensors are a rapidly growing area of research, due to graphene’s desirable properties, such as the ease of chemical functionalisation, high electrical conductivity, and high surface area. To achieve the required selectivity for this application area, graphene must be functionalised with an appropriate molecule, which can vary depending on the analyte under investigation. For some sensors, amine groups are required to bind to antibodies then used for the detection of biomarkers. However, there are a range of possible methods to functionalise graphene with amine, and the optimal method is still unclear.

Typically, covalent functionalisation is more durable, due to the greater bond strength, but this can disrupt the sp² carbon structure and thus degrade the electrical conductivity. Non-covalent functionalisation is expected to be less durable but maintains the sp² lattice and electrical conductivity. In our work we have investigated the differences between a covalent functionalisation, using 4-nitrobenzene diazonium tetrafluoroborate (4-NBD) to bind nitro-phenyl groups and subsequently phenyl amine groups to graphene, and a non-covalent functionalisation, using 1,5-Diaminonaphthalene (DAN) to form poly(1,5-diaminonaphthalene) (pDAN) layers on graphene.

The I_D/I_G ratio from the Raman spectra of graphene can be used as an indication of the level of disorder, and therefore can approximate the level of sp³ defects due to molecules bound to the graphene. Consequentially, it is typically used to confirm the success of a functionalisation process. However, Bissett, M. A et al. and Knirsch, K. C. et al. both previously reported unexpected changes in the I_D/I_G, where the I_D/I_G increased with functionalisation, but decreased again after an external force, due to strain and a chemical process respectively. Greenwood, J. et al. also reported changes in the Raman spectra after scanning tunnelling microscopy (STM) on functionalised highly oriented pyrolytic graphite (HOPG).

The work presented here on amine functionalised chemical vapor deposition (CVD) graphene shows that while covalent functionalisation is usually the method of choice, it is not necessarily preferable over non-covalent alternatives. Removal of functional groups from CVD graphene with contact-mode atomic force microscopy (AFM) explains unexpected changes in the Raman spectra, and suggests the durability of covalent functionalisation can be similar or worse than non-covalent functionalisation.

By using a combination of imaging techniques, we demonstrate some imaging challenges that can occur and the importance of using different analytical techniques to investigate the physicochemical properties of biosensors. Our characterisation combines the use of contact-mode AFM, tapping-mode AFM, Raman spectroscopy and time-of-flight secondary ion mass spectrometry (ToF-SIMS). We have also shown how different functionalisation processes affect the operation of a pH sensor, showing a higher sensitivity for the non-covalent process compared to the covalent process.

Electrical field effect sensors are an important class of devices that can enable point-of-care sensing by probing the intrinsic charge in the biological entity to be sensed. Use of graphene and especially curved or crumpled graphene for this application is especially promising. We have recently reported the lowest limit of detection (LoD) on electrical label-free field effect-based sensors using single or double stranded DNA molecules on the crumpled graphene FET platform. These devices with even millimeter scale channels show an ultra-high sensitivity detection in buffer and human serum sample down to 600 zM and 20 aM, respectively. Computational simulations reveal that the nanoscale deformations can form ‘electrical hot spots’ in the sensing channel which reduce the charge screening at the concave regions. We have also used the crumpled graphene field effect transistor-based biosensing of important biomarkers including small molecules and proteins. We show that dopamine can be captured by an aptamer and the conformation change of the probe molecule induced electrical signal changes in the sensor. Three different kinds of proteins were captured with specific antibodies including interleukin-6 (IL-6) and two viral proteins. All tested biomarkers were detectable with the highest sensitivity reported on a label-free electrical platform. Significantly, two COVID-19 related proteins, nucleocapsid (N-) and spike (S-) proteins antigens were successfully detected in PBS with extremely low LoDs. This label-free electrical tests can contribute to the challenge of rapid, point of care diagnostics for infectious disease and other important clinical conditions.

Nanoscale materials present excellent electrical and optical characteristics that can be harnessed for biosensing applications. Moreover, these materials are biocompatible and can be employed for cancer cell-specific detection, making them ideal candidates for bioelectrical sensing. Here, we developed an electrical-based biosensor based on one-dimensional (1D) materials with specific biosensing activity towards breast cancer cells. High sensitivity of the cancer cells were achieved within a hetrogenous population. Atomistic simulations and experimental studies indicate a 1D material-facilitated change in electrical conductivity. Our results provide a promising method of harnessing 1D materials for cell-specific bioelectrical sensing, and has the potential to recognize residual cancer cells within a clinical setting.

Liquid-phase exfoliation (LPE) [1] allows mass-scalable, cost-effective and versatile production of graphene and other 2-dimensional (2D) material formulations suitable for a wide range of applications. This approach can be also applied to biomedical applications, as LPE can be easily performed in water via non-covalent functionalisation with stabilisers. In particular, pyrene derivatives have shown to be more effective exfoliating agents than traditional surfactants and polymers [2], while providing defect-free 2D materials in water [3-4].

In this talk I will show that non-covalent functionalizion with pyrene derivatives is a simple one-pot approach that allows to make 2D material formulations with strong potential for biomedical applications. In particular, anionic, cationic and amphoteric graphene inks can be easily made by tuning the pyrene derivative used as stabilizer [5-7]. Cationic graphene dispersions show exceptional biocompatibility, intracellular uptake profile and stability in the biological medium, even with protein serum, making them a very attractive material for nanomedicine applications [7].
Finally, I will show that our graphene formulations can be used in combination with other materials to make a viscoelastic surface microelectrode array, which plastically deforms to allow conformation to the complex geometry of soft tissues such as brain [8].

[1] Hernandez, Y. et al. Nat. Nanotechnol. 3, 563 (2008)
[2] Parviz, D. et al. ACS Nano 6, 8857 (2012)
[3] Yang, H. et al. Carbon. 53, 357 (2013)
[4] Yang, H. et al, 2D Materials 1, 011012 (2014)
[5] Shin et al, Mol. Syst. Des. Eng., 2019, DOI:10.1039/C9ME00024K
[6] Shin et al, Faraday Discussion, https://doi.org/10.1039/C9FD00114J
[7] Shin et al, Nanoscale, 2020, DOI: 10.1039/D0NR02689A
[8] Tringides et al, just accepted

Molybdenum Disulfide (MoS2) has shown potential for applications in the field of electronic devices that can be used in the fields of bioelectronics to healthcare. In almost every application MoS2 is exposed to water or humidity, making it important to study the interactions between MoS2 and water. Here to explore the structure of water at the MoS2 surface, we have developed the non-bonded force-field (FF) parameters between the MoS2 surface and three different water models. A single-layered MoS2 surface was represented with Stillinger-Weber (SW) potential and SPC, SPC/E and SPC/Fw water models were used. In order to develop the non-bonded FF parameters, we have employed all-atom (AA) molecular dynamics (MD) simulations integrated with particle swarm optimization (PSO). The new parameters were optimized to reproduce the experimental contact angle of the water droplet on the MoS2 surface as well as the binding energy of a water molecule in four different orientations placed above the MoS2 surface. Using the newly developed parameters, we showed that the binding energies between water molecules and the MoS2 surface is equal to ~ -6.5 kJ/mol, which is in good agreement with the previously reported values in the literature. We have also analyzed the structural properties of water molecules in a droplet on a MoS2 sheet to validate the precision of the developed parameters. The analysis includes z-density profile of oxygen atoms, average hydrogen bond distribution per water molecule, and the angle made by the O-H vector with the normal to the MoS2 sheet.

Reduced graphene oxide has caused a flurry of excitement between researchers for its numerous applications including flexible electronics, biosensing, batteries, supercapacitors, photovoltaics, and optical devices. We report a simple and cost-effective method for the direct writing of reduced graphene oxide (rGO) from polytetrafluoroethylene (PTFE). The ArF excimer laser with a wavelength of 193 nm was utilized for the fast and non-equilibrium transition of PTFE into rGO in ambient conditions with no additional steps for the reduction of graphite. We show that this method has the capability of writing rGO from PTFE on different substrates. The Raman, SEM, and TEM studies indicated that an energy density window of 0.8-1.1 J.cm^-2 was necessary for providing the appropriate undercooling to form rGO structure. The studies suggested the mechanism of the transformation from PTFE into rGO is the photothermal process in which the chains of PTFE experience unzipping, melting, degassing of volatile components, and restructuring under the ablation threshold.

During epidemics or pandemics of emerging infections, personal protective equipment (PPE) is a critical non-pharmaceutical intervention that significantly reduces the spread of pathogens, especially when drugs and vaccines are unavailable. Due to many shortcomings of conventional PPE, there is a need for sustainable, re-usable high-performance PPE with antimicrobial properties. Herein, we report antimicrobial, biocompatible, and multifunctional cotton/silk fabrics coated with reduced graphene oxide (RGO) and silver (Ag)/copper (Cu) nanoparticles (NPs) by using a silane coupling agent followed by chemical reduction and vacuum heat treatment. Results reveal that due to the synergistic impact of NPs and RGO, incorporating a tiny amount of Cu and Ag NPs on top of the RGO boosts the bactericidal activity. All RGO-Ag/Cu NPs coated cotton/silk fabrics showed ~99% inhibition of Escherichia coli and Pseudomonas aeruginosa (Gram-negative bacterium). RGO−Ag NPs coated cotton/silk fabrics showed inhibition of 78−99% Staphylococcus aureus (Gram-positive bacterium). All the developed samples sustained their remarkable antimicrobial activity even after ten times washing. The RGO-Cu NPs cotton/silk demonstrated better inhibition of Candida albicans (Fungi), than all other samples. Additionally, developed fabrics exhibited lower cytotoxicity (<30%) than the pure, untreated fabrics, suggest good biocompatibility. These findings indicate that RGO− Cu/Ag NPs coated cotton/silk fabrics have excellent potential to be used in PPE development, such as protective clothing and face masks.

Introduction: Polycaprolactone (PCL)/Graphene nanocomposites emerge as promising scaffolds in biomedical applications owing to their unique properties. Understanding molecular level interactions of PCL/Graphene is inevitable to explore its potentials. Here we attempt a computational approach to study the interaction of PCL scaffold and Graphene nanoparticles using the software package, Compucell3D (CC3D). CC3D is a flexible, scriptable modeling environment, which allows the rapid construction of sharable virtual tissue in-silico simulations of a wide variety of multi-scale, multicellular problems.
Materials and Methods: The computational package, CC3D, used in this work is based on the Cellular Potts Model (CPM). CPM is a spatial lattice-based formalism that is extensively applied to understand complex multicellular behaviors in tissue morphogenesis. The technique is based on the free energy minimization using a dynamic Monte Carlo simulation algorithm where the cell behavior depends on a balance of forces described by the Hamiltonian function.
Results and Discussion: The biocompatibility of the PCL scaffold can be improved in the presence of graphene quantum dots due to their high electron mobility and conductivity. Attractive interaction between graphene and PCL is observed in the simulated results, which is primarily due to the natural hydrophobicity of graphene and PCL nanofibers. Van der Waal's interaction also contributes to the same. As the concentration of GQDs increases, the hydrophilicity of the scaffold increases, changing the trend in their interaction. Basic properties of the solvent like viscosity and chain length play an essential role in the scaffold's stability.
Conclusions: Simulation studies for PCL/Graphene interaction using CC3D were conducted. The results obtained indicate improved interaction of PCL and graphene. Reduced cytotoxicity of graphene GQDs is expected as PCL molecules surround it. Moreover, improvement in the diffusional properties of the system is anticipated. The simulation results are to be validated with experimental studies. Further simulation studies are to be conducted using CC3D to find out and optimize the parameters that influence the system and the system's permeability to check the efficiency of the same as a permeable membrane.