Wide bandgap semiconductor nanomembranes as a long-term biointerface for flexible, implanted neuromodulator.

Electrical neuron stimulation holds promise for treating chronic neurological disorders, including spinal cord injury, epilepsy, and Parkinson's disease. The implementation of ultrathin, flexible electrodes that can offer noninvasive attachment to soft neural tissues is a breakthrough for timely, continuous, programable, and spatial stimulations. With strict flexibility requirements in neural implanted stimulations, the use of conventional thick and bulky packages is no longer applicable, posing major technical issues such as short device lifetime and long-term stability. We introduce herein a concept of long-lived flexible neural electrodes using silicon carbide (SiC) nanomembranes as a faradic interface and thermal oxide thin films as an electrical barrier layer. The SiC nanomembranes were developed using a chemical vapor deposition (CVD) process at the wafer level, and thermal oxide was grown using a high-quality wet oxidation technique. The proposed material developments are highly scalable and compatible with MEMS technologies, facilitating the mass production of long-lived implanted bioelectrodes. Our experimental results showed excellent stability of the SiC/silicon dioxide (SiO2) bioelectronic system that can potentially last for several decades with well-maintained electronic properties in biofluid environments. We demonstrated the capability of the proposed material system for peripheral nerve stimulation in an animal model, showing muscle contraction responses comparable to those of a standard non-implanted nerve stimulation device. The design concept, scalable fabrication approach, and multimodal functionalities of SiC/SiO2 flexible electronics offer an exciting possibility for fundamental neuroscience studies, as well as for neural stimulation-based therapies.

Integrated Sensors for Soft Medical Robotics.

Minimally invasive procedures assisted by soft robots for surgery, diagnostics, and drug delivery have unprecedented benefits over traditional solutions from both patient and surgeon perspectives. However, the translation of such technology into commercialization remains challenging. The lack of perception abilities is one of the obstructive factors paramount for a safe, accurate and efficient robot-assisted intervention. Integrating different types of miniature sensors onto robotic end-effectors is a promising trend to compensate for the perceptual deficiencies in soft robots. For example, haptic feedback with force sensors helps surgeons to control the interaction force at the tool-tissue interface, impedance sensing of tissue electrical properties can be used for tumor detection. The last decade has witnessed significant progress in the development of multimodal sensors built on the advancement in engineering, material science and scalable micromachining technologies. This review article provides a snapshot on common types of integrated sensors for soft medical robots. It covers various sensing mechanisms, examples for practical and clinical applications, standard manufacturing processes, as well as insights on emerging engineering routes for the fabrication of novel and high-performing sensing devices.

Mesoporous Metastable CuTe2 Semiconductor.

Binary metastable semiconductor materials offer exciting possibilities in the field of optoelectronics, such as photovoltaics, tunable photosensors, and detectors. However, understanding their properties and translating them into practical applications can sometimes be challenging, owing to their thermodynamic instability. Herein, we report a temperature-controlled crystallization technique involving electrochemical deposition to produce metastable CuTe2 thin films that can reliably function under ambient conditions. A series of in situ heating/cooling cycle tests from room temperature to 200 °C followed by spectral, morphological, and compound analyses (such as ultraviolet-visible light spectroscopy, X-ray diffraction (XRD) analysis, and X-ray photoelectron spectroscopy (XPS)) suggest that the seeding electrodes play a key role in the realization of the metastable phase in CuTe2 films. In particular, CuTe2 films deposited on Al electrodes exhibit superior crystallinity and long-term stability compared with those grown on a Au substrate. The XRD data of thermally annealed CuTe2 thin films deposited on Al show a markedly sharp peak, indicating significantly increased crystal-domain sizes. Our method can be used to achieve the metastable phase of CuTe2 with a bandgap of 1.67 eV and offers outstanding photoresponsivity under different illumination conditions.

Flexible Nanoarchitectonics for Biosensing and Physiological Monitoring Applications.

Flexible and implantable electronics hold tremendous promises for advanced healthcare applications, especially for physiological neural recording and modulations. Key requirements in neural interfaces include miniature dimensions for spatial physiological mapping and low impedance for recognizing small biopotential signals. Herein, a bottom-up mesoporous formation technique and a top-down microlithography process are integrated to create flexible and low-impedance mesoporous gold (Au) electrodes for biosensing and bioimplant applications. The mesoporous architectures developed on a thin and soft polymeric substrate provide excellent mechanical flexibility and stable electrical characteristics capable of sustaining multiple bending cycles. The large surface areas formed within the mesoporous network allow for high current density transfer in standard electrolytes, highly suitable for biological sensing applications as demonstrated in glucose sensors with an excellent detection limit of 1.95 µm and high sensitivity of 6.1 mA cm-2  µM-1 , which is approximately six times higher than that of benchmarking flat/non-porous films. The low impedance of less than 1 kΩ at 1 kHz in the as-synthesized mesoporous electrodes, along with their mechanical flexibility and durability, offer peripheral nerve recording functionalities that are successfully demonstrated in vivo. These features highlight the new possibilities of our novel flexible nanoarchitectonics for neuronal recording and modulation applications.

Transparent Pneumatic Tactile Sensors for Soft Biomedical Robotics.

Palpation is a simple but effective method to distinguish tumors from healthy tissues. The development of miniaturized tactile sensors embedded on endoscopic or robotic devices is key to achieving precise palpation diagnosis and subsequent timely treatment. This paper reports on the fabrication and characterization of a novel tactile sensor with mechanical flexibility and optical transparency that can be easily mounted on soft surgical endoscopes and robotics. By utilizing the pneumatic sensing mechanism, the sensor offers a high sensitivity of 1.25 mbar and negligible hysteresis, enabling the detection of phantom tissues with different stiffnesses ranging from 0 to 2.5 MPa. Our configuration, combining pneumatic sensing and hydraulic actuating, also eliminates electrical wiring from the functional elements located at the robot end-effector, thereby enhancing the system safety. The optical transparency path in the sensors together with its mechanical sensing capability open interesting possibilities in the early detection of solid tumor as well as in the development of all-in-one soft surgical robots that can perform visual/mechanical feedback and optical therapy.

A Smart, Textile-Driven, Soft Exosuit for Spinal Assistance.

Work-related musculoskeletal disorders (WMSDs) are often caused by repetitive lifting, making them a significant concern in occupational health. Although wearable assist devices have become the norm for mitigating the risk of back pain, most spinal assist devices still possess a partially rigid structure that impacts the user's comfort and flexibility. This paper addresses this issue by presenting a smart textile-actuated spine assistance robotic exosuit (SARE), which can conform to the back seamlessly without impeding the user's movement and is incredibly lightweight. To detect strain on the spine and to control the smart textile automatically, a soft knitting sensor that utilizes fluid pressure as a sensing element is used. Based on the soft knitting hydraulic sensor, the robotic exosuit can also feature the ability of monitoring and rectifying human posture. The SARE is validated experimentally with human subjects (N = 4). Through wearing the SARE in stoop lifting, the peak electromyography (EMG) signals of the lumbar erector spinae are reduced by 22.8% ± 12 for lifting 5 kg weights and 27.1% ± 14 in empty-handed conditions. Moreover, the integrated EMG decreased by 34.7% ± 11.8 for lifting 5 kg weights and 36% ± 13.3 in empty-handed conditions. In summary, the artificial muscle wearable device represents an anatomical solution to reduce the risk of muscle strain, metabolic energy cost and back pain associated with repetitive lifting tasks.

Engineering Stress in Thin Films: An Innovative Pathway Toward 3D Micro and Nanosystems.

Transformation of conventional 2D platforms into unusual 3D configurations provides exciting opportunities for sensors, electronics, optical devices, and biological systems. Engineering material properties or controlling and modulating stresses in thin films to pop-up 3D structures out of standard planar surfaces has been a highly active research topic over the last decade. Implementation of 3D micro and nanoarchitectures enables unprecedented functionalities including multiplexed, monolithic mechanical sensors, vertical integration of electronics components, and recording of neuron activities in 3D organoids. This paper provides an overview on stress engineering approaches to developing 3D functional microsystems. The paper systematically presents the origin of stresses generated in thin films and methods to transform a 2D design into an out-of-plane configuration. Different types of 3D micro and nanostructures, along with their applications in several areas are discussed. The paper concludes with current technical challenges and potential approaches and applications of this fast-growing research direction.

Hydrogel Nanoarchitectonics: An Evolving Paradigm for Ultrasensitive Biosensing.

The integration of nanoarchitectonics and hydrogel into conventional biosensing platforms offers the opportunities to design physically and chemically controlled and optimized soft structures with superior biocompatibility, better immobilization of biomolecules, and specific and sensitive biosensor design. The physical and chemical properties of 3D hydrogel structures can be modified by integrating with nanostructures. Such modifications can enhance their responsiveness to mechanical, optical, thermal, magnetic, and electric stimuli, which in turn can enhance the practicality of biosensors in clinical settings. This review describes the synthesis and kinetics of gel networks and exploitation of nanostructure-integrated hydrogels in biosensing. With an emphasis on different integration strategies of hydrogel with nanostructures, this review highlights the importance of hydrogel nanostructures as one of the most favorable candidates for developing ultrasensitive biosensors. Moreover, hydrogel nanoarchitectonics are also portrayed as a promising candidate for fabricating next-generation robust biosensors.

Plasma-Induced Nanocrystalline Domain Engineering and Surface Passivation in Mesoporous Chalcogenide Semiconductor Thin Films.

The synthesis of highly crystalline mesoporous materials is key to realizing high-performance chemical and biological sensors and optoelectronics. However, minimizing surface oxidation and enhancing the domain size without affecting the porous nanoarchitecture are daunting challenges. Herein, we report a hybrid technique that combines bottom-up electrochemical growth with top-down plasma treatment to produce mesoporous semiconductors with large crystalline domain sizes and excellent surface passivation. By passivating unsaturated bonds without incorporating any chemical or physical layers, these films show better stability and enhancement in the optoelectronic properties of mesoporous copper telluride (CuTe) with different pore diameters. These results provide exciting opportunities for the development of long-term, stable, and high-performance mesoporous semiconductor materials for future technologies.

Digital Imaging-based Colourimetry for Enzymatic Processes in Transparent Liquid Marbles.

Liquid marbles are a promising microreactor platform that recently attracts significant research interest owing to their ability to accommodate a wide range of micro reactions. However, the use of destructive and ex-situ methods to monitor reactions impairs the potential of liquid-marble-based microreactors. This paper proposes a non-destructive, in situ, and cost-effective digital-imaging-based colourimetric monitoring method for transparent liquid marbles, using the enzymatic hydrolysis of starch as an illustrative example. The colourimetric reaction between starch and iodine produces a complex that exhibits a dark blue colour. We found that the absorbance of red channel of digital images showed a linear relationship with starch concentration with high sensitivity and repeatability. This digital-imaging-based colourimetric method was used to study the hydrolysis of starch by α-amylase. The results show high accuracy and applicability of first-order kinetics for this reaction. The demonstration of digital-imaging-based colourimetry indicates the potential of liquid marble-based microreactors.

Universal Electrochemical Synthesis of Mesoporous Chalcogenide Semiconductors: Mesoporous CdSe and CdTe Thin Films for Optoelectronic Applications.

Here we report the soft-template-assisted electrochemical deposition of mesoporous semiconductors (CdSe and CdTe). The resulting mesoporous films are stoichiometrically equivalent and contain mesopores homogeneously distributed over the entire surface. To demonstrate the versatility of the method, two block copolymers with different molecular weights are used, yielding films with pores of either 9 or 18 nm diameter. As a proof of concept, the mesoporous CdSe film-based photodetectors show a high sensitivity of 204 mW-1 cm2 at 680 nm wavelength, which is at least two orders of magnitude more sensitive than the bulk counterpart. This work presents a new synthesis route for nanostructured semiconductors with optical band gaps active in the visible spectrum.

Stretchable Inertial Microfluidic Device for Tunable Particle Separation.

Inertial microfluidics is a promising approach for particle separation because of the superior advantages of high throughput, simplicity, precise manipulation, and low cost. However, the current obstacle of inertial microfluidics in biological applications is the broad size distribution of biological microparticles. Most devices only work well for a narrow range of particle sizes. For focusing and separating a new set of particles, troublesome and time-consuming design, fabrication, testing, and optimization procedures are needed. As such, it is of particular interest to design a microfluidic device that can be tuned and adjusted to separate particles of various sizes. This paper reports on the proof of concept for a stretchable microfluidic device that can control the length via a stretching platform. By changing the channel dimensions, the device can be adapted to different particle sizes and flow rate ratios. We successfully demonstrate this approach with the separation of a mixture of 10 and 15 µm particles. Stretching the device significantly improves the focusing and separation efficiency of the specific particle sizes. We also show that there is an optimum stretching length, which results in the best separation performance. The proof of concept reported here is the first step toward designing stretchable inertial microfluidic devices that can be implemented for a wide range of biological and medical applications.

Advances in Rational Design and Materials of High-Performance Stretchable Electromechanical Sensors.

Stretchable and wearable sensor technology has attracted significant interests and created high technological impact on portable healthcare and smart human-machine interfaces. Wearable electromechanical systems are an important part of this technology that has recently witnessed tremendous progress toward high-performance devices for commercialization. Over the past few years, great attention has been paid to simultaneously enhance the sensitivity and stretchability of the electromechanical sensors toward high sensitivity, ultra-stretchability, low power consumption or self-power functionalities, miniaturisation as well as simplicity in design and fabrication. This work presents state-of-the-art advanced materials and rational designs of electromechanical sensors for wearable applications. Advances in various sensing concepts and structural designs for intrinsic stretchable conductive materials as well as advanced rational platforms are discussed. In addition, the practical applications and challenges in the development of stretchable electromechanical sensors are briefly mentioned and highlighted.

Functional Microarray Platform with Self-Assembled Monolayers on 3C-Silicon Carbide.

Currently available bioplatforms such as microarrays and surface plasmon resonators are unable to combine high-throughput multiplexing with label-free detection. As such, emerging microelectromechanical systems (MEMS) and microplasmonics platforms offer the potential for high-resolution, high-throughput label-free sensing of biological and chemical analytes. Therefore, the search for materials capable of combining multiplexing and label-free quantitation is of great significance. Recently, interest in silicon carbide (SiC) as a suitable material in numerous biomedical applications has increased due to its well-explored chemical inertness, mechanical strength, bio- and hemocompatibility, and the presence of carbon that enables the transfer-free growth of graphene. SiC is also multifunctional as both a wide-band-gap semiconductor and an efficient low-loss plasmonics material and thus is ideal for augmenting current biotransducers in biosensors. Additionally, the cubic variant, 3C-SiC, is an extremely promising material for MEMS, being a suitable platform for the easy micromachining of microcantilevers, and as such capable of realizing the potential of real time miniaturized multiplexed assays. The generation of an appropriately functionalized and versatile organic monolayer suitable for the immobilization of biomolecules is therefore critical to explore label-free, multiplexed quantitation of biological interactions on SiC. Herein, we address the use of various silane self-assembled monolayers (SAMs) for the covalent functionalization of monocrystalline 3C-SiC films as a novel platform for the generation of functionalized microarray surfaces using high-throughput glycan arrays as the model system. We also demonstrate the ability to robotically print high throughput arrays on free-standing SiC microstructures. The implementation of a SiC-based label-free glycan array will provide a proof of principle that could be extended to the immobilization of other biomolecules in a similar SiC-based array format, thus making potentially significant advances to the way biological interactions are studied.

Avoiding Pre-Isolation Step in Exosome Analysis: Direct Isolation and Sensitive Detection of Exosomes Using Gold-Loaded Nanoporous Ferric Oxide Nanozymes.

Most of the current exosome-analysis strategies are time-consuming and largely dependent on commercial extraction kit-based preisolation step, which requires extensive sample manipulations, costly isolation kits, reagents, tedious procedures, and sophisticated equipment and is prone to bias/artifacts. Herein we introduce a simple method for direct isolation and subsequent detection of a specific population of exosomes using an engineered superparamagnetic material with multifunctional properties, namely, gold-loaded ferric oxide nanocubes (Au-NPFe2O3NC). In this method, the Au-NPFe2O3NC were initially functionalized with a generic tetraspanin (exosomes-associated) antibody (i.e., CD63) and dispersed in sample fluids where they work as "dispersible nanocarriers" to capture the bulk population of exosomes. After magnetic collection and purification, Au-NPFe2O3NC-bound exosomes were transferred to the tissue-specific, antibody-modified, screen-printed electrode. As a proof of principle, we used a specific placental marker, placenta alkaline phosphatase (PLAP), to detect exosomes secreted from placental cells. The peroxidase-like activity of Au-NPFe2O3NC was then used to accomplish an enzyme-linked immunosorbent assay (ELISA)-based sensing protocol for naked-eye observation along with UV-visible and electrochemical detection of PLAP-specific exosomes present in placental cell-conditioned media. We demonstrated excellent agreement in analytical performance for the detection of placental cell-derived exosomes (i.e., linear dynamic range, 103-107 exosomes/mL; limit of detection, 103 exosomes/mL; relative standard deviation (%RSD) of <5.5% for n = 3) using with and without commercial "total exosome isolation kit"-based preisolation step. We envisage that this highly sensitive, rapid, and inexpensive assay could be useful in quantifying specific populations of exosomes for various clinical applications, focusing on pregnancy complications.

Naked-eye and electrochemical detection of isothermally amplified HOTAIR long non-coding RNA.

An inexpensive, simple and rapid sensor platform capable of detecting cancer-related long non-coding RNA (lncRNA) with high accuracy is of great interest in the field of molecular diagnostics. Herein, we report on the development of a new colorimetric and electrochemical assay platform for long non-coding HOX transcript antisense intergenic RNA (HOTAIR) detection. Isothermal reverse transcription-recombinase polymerase amplification (RT-RPA) was performed to amplify HOTAIR sequences from a RNA pool extracted from a designated number of ovarian cancer cells and a small cohort of plasma samples derived from patients with ovarian cancer. During RT-RPA, biotinylated dUTPs were randomly incorporated in the amplified product. Subsequently, HOTAIR amplicons were magnetically purified and isolated followed by a horseradish peroxidase (HRP)-catalyzed colorimetric reaction in the presence of the 3,3',5,5'-tetramethylbenzidine (TMB)/H2O2 system. We finally introduced three potential readout methods for HOTAIR detection - (i) naked-eye visualisation of the color change for a quick screening of the target, (ii) quantitative absorbance measurement by UV-vis, and (iii) amperometric quantification using the electrochemical properties of TMB. The assay has shown excellent reproducibility (% RSD = <5%, for n = 3) and sensitivity (10 cells/ per mL) while detecting HOTAIR in cancer cell lines and patient samples. The expression of HOTAIR in clinical samples was also verified with a standard RT-qPCR method. We believe that our proof of concept assay may find potential relevance for the routine clinical screening of cancer-associated lncRNAs.

Low-Cost Graphite on Paper Pressure Sensor for a Robot Gripper with a Trivial Fabrication Process.

A flexible pressure sensor with a rudimentary, ultra-low cost, and solvent-free fabrication process is presented in this paper. The sensor has a graphite-on-paper stacked paper structure, which deforms and restores its shape when pressure is applied and released, showing an exceptionally fast response and relaxation time of ≈0.4 ms with a sensitivity of -5%/Pa. Repeatability of the sensor over 1000 cycles indicates an excellent long-term stability. The sensor demonstrated fast and reliable human touch interface, and successfully integrated into a robot gripper to detect grasping forces, showing high promise for use in robotics, human interface, and touch devices.

Thermal Flow Sensors for Harsh Environments.

Flow sensing in hostile environments is of increasing interest for applications in the automotive, aerospace, and chemical and resource industries. There are thermal and non-thermal approaches for high-temperature flow measurement. Compared to their non-thermal counterparts, thermal flow sensors have recently attracted a great deal of interest due to the ease of fabrication, lack of moving parts and higher sensitivity. In recent years, various thermal flow sensors have been developed to operate at temperatures above 500 °C. Microelectronic technologies such as silicon-on-insulator (SOI), and complementary metal-oxide semiconductor (CMOS) have been used to make thermal flow sensors. Thermal sensors with various heating and sensing materials such as metals, semiconductors, polymers and ceramics can be selected according to the targeted working temperature. The performance of these thermal flow sensors is evaluated based on parameters such as thermal response time, flow sensitivity. The data from thermal flow sensors reviewed in this paper indicate that the sensing principle is suitable for the operation under harsh environments. Finally, the paper discusses the packaging of the sensor, which is the most important aspect of any high-temperature sensing application. Other than the conventional wire-bonding, various novel packaging techniques have been developed for high-temperature application.

Novel Low-Cost Sensor for Human Bite Force Measurement.

This paper presents the design and development of a low cost and reliable maximal voluntary bite force sensor which can be manufactured in-house by using an acrylic laser cutting machine. The sensor has been designed for ease of fabrication, assembly, calibration, and safe use. The sensor is capable of use within an hour of commencing production, allowing for rapid prototyping/modifications and practical implementation. The measured data shows a good linear relationship between the applied force and the electrical resistance of the sensor. The output signal has low drift, excellent repeatability, and a large measurable range of 0 to 700 N. A high signal-to-noise response to human bite forces was observed, indicating the high potential of the proposed sensor for human bite force measurement.

Enhanced Photovoltaic Effect in n-3C-SiC/p-Si Heterostructure Using a Temperature Gradient for Microsensors.

The development of fifth-generation (5G) communications and the Internet of Things (IoT) has created a need for high-performance sensing networks and sensors. Improving the sensitivity and reducing the energy consumption of these sensors can improve the performance of the sensing network and conserve energy. This paper reports a large enhancement of the photovoltaic effect in a 3C-SiC/Si heterostructure and the tunability of the photovoltage under the impact of a temperature gradient, which has the potential to increase the sensitivity and reduce the energy consumption of microsensors. To start with, cubic silicon carbide (3C-SiC) was grown on a silicon wafer, and a micro-3C-SiC/Si heterostructure device was then fabricated using standard photolithography. The result revealed that the sensor could either capture light energy, transform it into electrical energy for self-power purposes, or detect light with intensities of 1.6 and 4 mW/cm2. Under the impact of the temperature gradient induced by conduction heat transfer from a heater, the measured photovoltage was improved. This thermo-phototronic coupling enhanced the photovoltage up to 51% at a temperature gradient of 8.73 K and light intensity of 4 mW/cm2. Additionally, the enhancement can be tuned by controlling the direction of the temperature gradient and the temperature difference. These findings indicate the promise of the temperature gradient in SiC/Si heterostructures for developing high-performance temperature sensors and self-powered photodetectors.