Biointerface Applications Research Articles

Silk‐based conductive materials for smart biointerfaces (2/2023)

Silk-based conductive materials are widely used in bio interface applications, such as artificial epidermal sensors, soft and implantable bioelectronics, and tissue/cell scaffolds. In this article, Fu and coworkers reviewed the advanced paradigms of these conductive silk materials, with perspectives on the application challenges.

Silk-based conductive materials for smart biointerfaces.

Silk-based conductive materials are widely used in biointerface applications, such as artificial epidermal sensors, soft and implantable bioelectronics, and tissue/cell scaffolds. Such biointerface materials require coordinated physicochemical, biological, and mechanical properties to meet current practical needs and future sophisticated demands. However, it remains a challenge to formulate silk-based advanced materials with high electrical conductivity, good biocompatibility, mechanical robustness, and in some cases, tissue adhesion ability without compromising other physicochemical properties. In this review, we highlight recent progress in the development of functional conductive silk-based advanced materials with different morphologies. Then, we reviewed the advanced paradigms of these silk materials applied as wearable flexible sensors, implantable electronics, and tissue/cell engineering with perspectives on the application challenges. Silk-based conductive materials can serve as promising building blocks for biomedical devices in personalized healthcare and other fields of bioengineering.

High‐Conductivity Stoichiometric Titanium Nitride for Bioelectronics

AbstractBioelectronic devices such as neural stimulation and recording devices require stable low‐impedance electrode interfaces. Various forms of nitridated titanium are used in biointerface applications due to robustness and biological inertness. In this work, stoichiometric TiN thin films are fabricated using a dual Kaufman ion‐beam source setup, without the necessity of substrate heating. These layers are remarkable compared to established forms of TiN due to high degree of crystallinity and excellent electrical conductivity. How this fabrication method can be extended to produce structured AlN, to yield robust AlN/TiN bilayer micropyramids, is described. These electrodes compare favorably to commercial TiN microelectrodes in the performance metrics important for bioelectronics interfaces: higher conductivity (by an order of magnitude), lower electrochemical impedance, and higher capacitive charge injection with lower faradaicity. These results demonstrate that the Kaufman ion‐beam sputtering method can produce competitive nitride ceramics for bioelectronics applications at low deposition temperatures.

Correlation of Cell Proliferation with Surface Properties of Polymer-like Carbon Films of Different Thicknesses Prepared by a Radio-Frequency Plasma CVD Process.

In this study, correlation of cell proliferation with surface properties of the polymer-like carbon (PLC) films of different thicknesses prepared by radio-frequency plasma CVD are investigated. Four PLC samples were prepared via radio frequency plasma chemical vapor deposition on Si substrates. Each PLC film was analyzed using spectroscopic ellipsometry to determine its thickness, refractive index (n), and extinction coefficient (k); the thickness ranged from 29.0 to 356.5 nm. Based on their n–k plots, all the samples were classified as PLC-type films. The biological response of the PLC films was evaluated in vitro using a cell culture. The samples with relatively thick PLC films (>300 nm) exhibited stronger cell proliferation properties than those with thinner films. Moreover, the results of the surface analysis showed no significant differences in the surface composition of those PLC samples, as analyzed using X-ray photoelectron spectroscopy, but that as the PLC films became thicker, their surfaces became rougher on the nanoscale and their wettability improved. Overall, this study showed that careful control of the film growth of PLC films, which affects their surface properties, is essential for their use in bio-interface applications.

Atomic Layers of Graphene for Microbial Corrosion Prevention.

Graphene is a promising material for many biointerface applications in engineering, medical, and life-science domains. Here, we explore the protection ability of graphene atomic layers to metals exposed to aggressive sulfate-reducing bacteria implicated in corrosion. Although the graphene layers on copper (Cu) surfaces did not prevent the bacterial attachment and biofilm growth, they effectively restricted the biogenic sulfide attack. Interestingly, single-layered graphene (SLG) worsened the biogenic sulfide attack by 5-fold compared to bare Cu. In contrast, multilayered graphene (MLG) on Cu restricted the attack by 10-fold and 1.4-fold compared to SLG-Cu and bare Cu, respectively. We combined experimental and computational studies to discern the anomalous behavior of SLG-Cu compared to MLG-Cu. We also report that MLG on Ni offers superior protection ability compared to SLG. Finally, we demonstrate the effect of defects, including double vacancy defects and grain boundaries on the protection ability of atomic graphene layers.

Laser writing of nitrogen-doped silicon carbide for biological modulation.

Conducting or semiconducting materials embedded in insulating polymeric substrates can be useful in biointerface applications; however, attainment of this composite configuration by direct chemical processes is challenging. Laser-assisted synthesis has evolved as a fast and inexpensive technique to prepare various materials, but its utility in the construction of biophysical tools or biomedical devices is less explored. Here, we use laser writing to convert portions of polydimethylsiloxane (PDMS) into nitrogen-doped cubic silicon carbide (3C-SiC). The dense 3C-SiC surface layer is connected to the PDMS matrix via a spongy graphite layer, facilitating electrochemical and photoelectrochemical activity. We demonstrate the fabrication of arbitrary two-dimensional (2D) SiC-based patterns in PDMS and freestanding 3D constructs. To establish the functionality of the laser-produced composite, we apply it as flexible electrodes for pacing isolated hearts and as photoelectrodes for local peroxide delivery to smooth muscle sheets.

One-step and large-scale fabrication of flexible and wearable humidity sensor based on laser-induced graphene for real-time tracking of plant transpiration at bio-interface

The rapidly growing demand for humidity sensing in various applications such as noninvasive epidermal sensing, water status tracking of plants, and environmental monitoring has triggered the development of high-performance humidity sensors. In particular, timely communication with plants to understand their physiological status may facilitate preventing negative influence of environmental stress and enhancing agricultural output. In addition, precise humidity sensing at bio-interface requires the sensor to be both flexible and stable. However, challenges still exist for the realization of efficient and large-scale production of flexible humidity sensors for bio-interface applications. Here, a convenient, effective, and robust method for massive production of flexible and wearable humidity sensor is proposed, using laser direct writing technology to produce laser-induced graphene interdigital electrode (LIG-IDE). Compared to previous methods, this strategy abandons the complicated and costly procedures for traditional IDE preparation. Using graphene oxide (GO) as the humidity-sensitive material, a flexible capacitive-type GO-based humidity sensor with low hysteresis, high sensitivity (3215.25 pF/% RH), and long-term stability (variation less than ± 1%) is obtained. These superior properties enable the sensor with multifunctional applications such as noncontact humidity sensing and human breath monitoring. In addition, this flexible humidity sensor can be directly attached onto the plant leaves for real-time and long-term tracking transpiration from the stomata, without causing any damage to plants, making it a promising candidate for next-generation electronics for intelligent agriculture.

Bio‐interface behaviour of graphene and semiconducting SWCNT:C60blend based nano photodiode for subretinal implant

Hybrid interfaces between living cells and organic conjugated polymers play a pivotal role in bioelectronics medicine. Currently, conjugated polymers are widely utilised for optical stimulation of living cells and other bio-interface applications such as neural probes, cellular scaffolds and biosensors for drug release. In such a work, the authors fabricated and characterised the Nano Photodiode array device for the subretinal implant. However, the authors did not discuss in their report about the biocompatibility of this new device. In this work, the authors manifest that the quintessential graphene electrode and polymer blend of semiconducting single-wall carbon nanotube and C60 fullerene (S-SWCNT:C60) sustains its optoelectronic properties all through the various strides for neural preparation. Further, the studies show that these materials can provide a favourable environment for cell proliferation and a high degree of biocompatibility. PC-12 cells used as a valuable model to validate the biocompatibility were grown successfully onto the S-SWCNT:C60 active layer still preserving its optical and electrical properties. The improved electrical performance of nano photodiode made of graphene, S-SWCNT:C60 established in the previous studies and the excellent bio-interface performance of this nano photodiode shows that the nano photodiode array proposed by the authors is a strong candidate for subretinal implants.

Decoration of Material Surfaces with Complex Physicochemical Signals for Biointerface Applications.

The surface properties of biomaterials are crucial at controlling biological interactions. Cells or tissues sense different stimuli from surfaces and respond accordingly. A number of studies have reported that fabricating complex stimuli-presenting surfaces is beneficial for mimicking and understanding the in vivo scenario where multi-physicochemical cues are present. Biological responses toward these surfaces could be either negative, such as immune responses, or positive, such as tissue regeneration. An ideal material surface should, therefore, be multifunctional, triggering the desired biological process and suppressing the unwanted side effects. The methods for material surface decoration can be very sophisticated, depending on the applications such as biosensors, medical devices, and/or implants. To date, decorating material surfaces with complex chemistries and topographies is still challenging, and methods are not straightforward. The majority of the methods require multiple steps and combinational approaches that include mask-based techniques, lithography, wet or dry etching, wet chemistry, or vapor-based coatings, among others. Although these methods have been established in the laboratory, easy-to-access and straightforward approaches need to be explored. This Review summarizes the state-of-the-art techniques for generating patterned multichemical and multitopographic signals on material surfaces, and the potential of having these surfaces in biointerface applications.

Non-equilibrium hybrid organic plasma processing for superhydrophobic PTFE surface towards potential bio-interface applications

Superhydrophobic surfaces have gained increased attention due to the high water-repellency and self-cleaning capabilities of these surfaces. In the present study, we explored a novel hybrid method of fabricating superhydrophobic poly(tetrafluoroethylene) (PTFE) surfaces by combining the physical etching capability of oxygen plasma with the plasma-induced polymerization of a organic monomer methyl methacrylate (MMA). This novel hybrid combination of oxygen-MMA plasma has resulted in the generation of superhydrophobic PTFE surfaces with contact angle of 154°. We hypothesized that the generation of superhydrophobicity may be attributed to the generation of fluorinated poly(methyl methacrylate) (PMMA) moieties formed by the combined effects of physical etching causing de-fluorination of PTFE and the subsequent plasma polymerization of MMA. The plasma treated PTFE surfaces were then systematically characterized via XPS, FTIR, XRD, DSC and SEM analyses. The results have clearly shown a synergistic effect of the oxygen/MMA combination in comparison with either the oxygen plasma alone or MMA vapors alone. Furthermore, the reported new hybrid combination of Oxygen-MMA plasma has been demonstrated to achieve superhydrophobicity at lower power and short time scales than previously reported methods in the literature. Hence the reported novel hybrid strategy of fabricating superhydrophobic PTFE surfaces could have futuristic potential towards biointerface applications.

Fabrication of Iridium Oxide/Platinum Composite Film on Titanium Substrate for High-Performance Neurostimulation Electrodes

Electrode materials for neural stimulation have been widely investigated for implantable devices. Among them, iridium and iridium oxide are attractive materials for bio-interface applications due to their desirable stability, electrochemical performance, and biocompatibility. In this study, iridium oxide/platinum (IrOx/Pt) composite films were successfully fabricated on titanium substrates by chemical bath deposition and these films are expected to be used as biocompatible stimulation electrodes. We modified the film compositions to optimize the performances. In addition, these IrOx/Pt composite films were characterized before and after annealing by SEM and XRD. We also identified the hydrophilicity of these iridium oxide/platinum composite films by measuring contact angles. Finally, the charge storage capacities of these iridium oxide/platinum composite films were evaluated by an electrochemical workstation. As a result, the charge storage capacities of the iridium oxide/platinum composite films are largely increased, and this leads to a very efficient neurostimulation electrode. Additionally, we successfully demonstrated the chemical bath deposition of IrOx film on the surface of the bullet-shaped titanium microelectrode.

Fabrication of Nanoporous IrO₂/Ir Films for Bioelectrode and Neural Prosthesis Applications.

IrO₂ and Ir are attractive materials for bio-interface applications due to their desirable stability, electrochemical performance, and biocompatibility. Nanostructured IrO₂/Ir possesses several advantageous properties including large surface-to-volume ratio, light weight, super hydrophilic surface, desirable electrochemical capability, and cell adhesion. Herein, we employ a cost-effective process to fabricate uniform nanoporous IrO₂/Ir film by chemical bath deposition, high-vacuum annealing, and electrochemical activation. High-vacuum annealing can remove oxygen from an IrO₂ film to create a nanoporous structure, and we determine the optimized electrochemical activation to transform Ir to IrO₂/Ir. The surface morphology, roughness, hydrophilicity, crystallinity, oxidation state, and charge storage capacity (CSC) of the films were analyzed. The nanoporous IrO₂/Ir film showed a 25% increase of CSC compared to the dense IrO₂ film, and this excellent performance makes it a promising candidate for bio-interface applications. In addition, this fabrication route can be cost-effective process without wasting the expensive noble metal Ir material.

Physical and biophysical assessment of highly fluorescent, magnetic quantum dots of a wurtzite-phase manganese selenide system

Combining fluorescence and magnetic features in a non-iron based, select type of quantum dots (QDs) can have immense value in cellular imaging, tagging and other nano–bio interface applications, including targeted drug delivery. Herein, we report on the colloidal synthesis and physical and biophysical assessment of wurtzite-type manganese selenide (MnSe) QDs in cell culture media. Aiming to provide a suitable colloidal system of biological relevance, different concentrations of reactants and ligands (e.g., thioglycolic acid, TGA) have been considered. The average size of the QDs is ∼7 nm, which exhibited a quantum yield of ∼75% as compared to rhodamine 6 G dye®. As revealed from time-resolved photoluminescence (TR-PL) response, the near band edge emission followed a bi-exponential decay feature with characteristic times of ∼0.64 ns and 3.04 ns. At room temperature, the QDs were found to exhibit paramagnetic features with coercivity and remanence impelled by TGA concentrations. With BSA as a dispersing agent, the QDs showed an improved optical stability in Dulbecco’s Modified Eagle Media® (DMEM) and Minimum Essential Media® (MEM), as compared to the Roswell Park Memorial Institute® (RPMI-1640) media. Finally, the cell viability of lymphocytes was found to be strongly influenced by the concentration of MnSe QDs, and had a safe limit upto 0.5 μM. With BSA inclusion in cell media, the cellular uptake of MnSe QDs was observed to be more prominent, as revealed from fluorescence imaging. The fabrication of water soluble, nontoxic MnSe QDs would open up an alternative strategy in nanobiotechnology, while preserving their luminescent and magnetic properties intact.

Cyclic olefin copolymer based microfluidic devices for biochip applications: Ultraviolet surface grafting using 2-methacryloyloxyethyl phosphorylcholine

This report studies the surface modification of cyclic olefin copolymer (COC) by 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer using photografting technique for the purpose of biointerface applications, which demonstrate resistance to both protein adsorption and cell adhesion in COC-based microfluidic devices. This is essential because the hydrophobic nature of COC can lead to adsorption of specific compounds from biological fluids in the microchannel, which can affect the results during fluidic analysis and cause clogging inside the microchannel. A correlation was found between the irradiation time and hydrophobicity of the modified substrate. Static water contact angle results show that the hydrophilicity property of the MPC-grafted substrate improves with increasing irradiation time. The contact angle of the modified surface decreased to 20 ± 5° from 88 ± 3° for the untreated substrate. The surface characterization of the modified surface was evaluated using x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR spectroscopy). Attenuated total reflection-FTIR and XPS results show the presence of the phosphate group (P-O) on modified COC substrates, indicating that the hydrophilic MPC monomer has successfully grafted on COC. Finally, it was demonstrated that cell adhesion and protein adsorption on the MPC modified COC specimen has reduced significantly.

Reversible Shape Memory of Nanoscale Deformations in Inherently Conducting Polymers without Reprogramming

By using inherently conducting polymers, we introduce new shape memory functionality for stimuli-responsive polymers. The shape memory process is unique in that it utilizes electrochemical control of the polymer redox state to conceal, and temporarily store, preformed nanoscale surface patterns, which can later be recalled. Unlike classical thermoset and thermoplastic shape memory polymers, the electrochemical control does not completely perturb the low entropy state of the deformed polymer chains, thus enabling the concept of reversible transition between the permanent and temporary shapes. This is demonstrated using electrochemical-atomic force microscopy/quartz crystal microbalance to characterize the modulation of nanoscale deformations in electroactive polybithiophene films. Experimental results reveal that cation/solvent exchange with the electrolyte and its effect on reconfiguration of the film structure is the mechanism behind the process. In addition to incorporating conductive properties into shape-memory polymers, the ability to reversibly modulate surface nanopatterns in a liquid environment is also of significant interest in tribology and biointerface applications.

High Affinity Anti-inorganic Material Antibody Generation by Integrating Graft and Evolution Technologies: POTENTIAL OF ANTIBODIES AS BIOINTERFACE MOLECULES

Recent advances in molecular evolution technology enabled us to identify peptides and antibodies with affinity for inorganic materials. In the field of nanotechnology, the use of the functional peptides and antibodies should aid the construction of interface molecules designed to spontaneously link different nanomaterials; however, few material-binding antibodies, which have much higher affinity than short peptides, have been identified. Here, we generated high affinity antibodies from material-binding peptides by integrating peptide-grafting and phage-display techniques. A material-binding peptide sequence was first grafted into an appropriate loop of the complementarity determining region (CDR) of a camel-type single variable antibody fragment to create a low affinity material-binding antibody. Application of a combinatorial library approach to another CDR loop in the low affinity antibody then clearly and steadily promoted affinity for a specific material surface. Thermodynamic analysis demonstrated that the enthalpy synergistic effect from grafted and selected CDR loops drastically increased the affinity for material surface, indicating the potential of antibody scaffold for creating high affinity small interface units. We show the availability of the construction of antibodies by integrating graft and evolution technology for various inorganic materials and the potential of high affinity material-binding antibodies in biointerface applications.

Atomic precision lithography on Si

Lithographic precision is as or more important than resolution. For decades, the semiconductor industry has been able to work with ±5% precision. However, for other applications such as micronanoelectromechanical systems, optical elements, and biointerface applications, higher precision is desirable. Lyding et al. [Appl. Phys. Lett. 64, 11 (1999)] have demonstrated that a scanning tunneling microscope can be used to remove hydrogen (H) atoms from a silicon (100) 2 × 1 H-passivated surface through an electron stimulated desorption process. This can be considered e-beam lithography with a thin, self-developing resist. Patterned hydrogen layers do not make a robust etch mask, but the depassivated areas are highly reactive since they are unsatisfied covalent bonds and have been used for selective deposition of metals, oxides, semiconductors, and dopants. The depassivation lithography has shown the ability to remove single H atoms, suggesting the possibility of precise atomic patterning. This patterning process is being developed as part of a project to develop atomically precise patterned atomic layer epitaxy of silicon. However, significant challenges in sample preparation, tip technology, subnanometer pattern placement, and patterning throughput must be overcome before an automated atomic precision lithographic technology evolves.