A wirelessly programmable, skin-integrated thermo-haptic stimulator system for virtual reality.

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.

A Blood Drying Process for DNA Amplification.

The presence of numerous inhibitors in blood makes their use in nucleic acid amplification techniques difficult. Current methods for extracting and purifying pathogenic DNA from blood involve removal of inhibitors, resulting in low and inconsistent DNA recovery rates. To address this issue, a biphasic method is developed that simultaneously achieves inhibitor inactivation and DNA amplification without the need for a purification step. Inhibitors are physically trapped in the solid-phase dried blood matrix by blood drying, while amplification reagents can move into the solid nano-porous dried blood and initiate the amplification. It is demonstrated that the biphasic method has significant improvement in detection limits for bacteria such as Escherichia coli, Methicillin-resistant Staphylococcus aureus, Methicillin-Sensitive Staphylococcus aureus using loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA). Several factors, such as drying time, sample volume, and material properties are characterized to increase sensitivity and expand the application of the biphasic assay to blood diagnostics. With further automation, this biphasic technique has the potential to be used as a diagnostic platform for the detection of pathogens eliminating lengthy culture steps.

Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Ultrasensitive Detection of SARS-CoV-2 in Saliva and Viral Transport Medium Clinical Samples.

The COVID-19 pandemic has underscored the shortcomings in the deployment of state-of-the-art diagnostics platforms. Although several polymerase chain reaction (PCR)-based techniques have been rapidly developed to meet the growing testing needs, such techniques often need samples collected through a swab, the use of RNA extraction kits, and expensive thermocyclers in order to successfully perform the test. Isothermal amplification-based approaches have also been recently demonstrated for rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by minimizing sample preparation while also reducing the instrumentation and reaction complexity. In addition, there are limited reports of saliva as the sample source, and some of these indicate inferior sensitivity when comparing reverse transcription loop-mediated isothermal amplification (RT-LAMP) with PCR-based techniques. In this paper, we demonstrate an improved sensitivity assay from saliva using a two-step RT-LAMP assay, where a short 10 min RT step is performed with only B3 and backward inner primers before the final reaction. We show that while the one-step RT-LAMP demonstrates satisfactory results, the optimized two-step approach allows detection of only few molecules per reaction and performs significantly better than the one-step RT-LAMP and conventional two-step RT-LAMP approaches with all primers included in the RT step. We show control measurements with RT-PCR, and importantly, we demonstrate RNA extraction-free RT-LAMP-based assays for detection of SARS-CoV-2 from viral transport media and saliva clinical samples.

Remote control of muscle-driven miniature robots with battery-free wireless optoelectronics.

Bioengineering approaches that combine living cellular components with three-dimensional scaffolds to generate motion can be used to develop a new generation of miniature robots. Integrating on-board electronics and remote control in these biological machines will enable various applications across engineering, biology, and medicine. Here, we present hybrid bioelectronic robots equipped with battery-free and microinorganic light-emitting diodes for wireless control and real-time communication. Centimeter-scale walking robots were computationally designed and optimized to host on-board optoelectronics with independent stimulation of multiple optogenetic skeletal muscles, achieving remote command of walking, turning, plowing, and transport functions both at individual and collective levels. This work paves the way toward a class of biohybrid machines able to combine biological actuation and sensing with on-board computing.

Microfluidic point-of-care device for detection of early strains and B.1.1.7 variant of SARS-CoV-2 virus.

Since the beginning of the COVID-19 pandemic, several mutations of the SARS-CoV-2 virus have emerged. Current gold standard detection methods for detecting the virus and its variants are based on PCR-based diagnostics using complex laboratory protocols and time-consuming steps, such as RNA isolation and purification, and thermal cycling. These steps limit the translation of technology to the point-of-care and limit accessibility to under-resourced regions. While PCR-based assays currently offer the possibility of multiplexed gene detection, and commercial products of single gene PCR and isothermal LAMP at point-of-care are also now available, reports of isothermal assays at the point-of-care with detection of multiple genes are lacking. Here, we present a microfluidic assay and device to detect and differentiate the Alpha variant (B.1.1.7) from the SARS-CoV-2 virus early strains in saliva samples. The detection assay, which is based on isothermal RT-LAMP amplification, takes advantage of the S-gene target failure (SGTF) to differentiate the Alpha variant from the SARS-CoV-2 virus early strains using a binary detection system based on spatial separation of the primers specific to the N- and S-genes. We use additively manufactured plastic cartridges in a low-cost optical reader system to successfully detect the SARS-CoV-2 virus from saliva samples (positive amplification is detected with concentration ≥10 copies per µL) within 30 min. We demonstrate that our platform can discriminate the B.1.1.7 variant (USA/CA_CDC_5574/2020 isolate) from SARS-CoV-2 negative samples, but also from the SARS-CoV-2 USA-WA1/2020 isolate. The reliability of the developed point-of-care device was confirmed by testing 38 clinical saliva samples, including 20 samples positive for Alpha variant (sensitivity > 90%, specificity = 100%). This study highlights the current relevance of binary-based testing, as the new Omicron variant also exhibits S-gene target failure and could be tested by adapting the approach presented here.

Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue.

Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young's modulus of skin and of other soft tissues at depths of approximately 1-8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders.

Battery-free, wireless soft sensors for continuous multi-site measurements of pressure and temperature from patients at risk for pressure injuries.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.

Catheter-integrated soft multilayer electronic arrays for multiplexed sensing and actuation during cardiac surgery.

The rigidity and relatively primitive modes of operation of catheters equipped with sensing or actuation elements impede their conformal contact with soft-tissue surfaces, limit the scope of their uses, lengthen surgical times and increase the need for advanced surgical skills. Here, we report materials, device designs and fabrication approaches for integrating advanced electronic functionality with catheters for minimally invasive forms of cardiac surgery. By using multiphysics modelling, plastic heart models and Langendorff animal and human hearts, we show that soft electronic arrays in multilayer configurations on endocardial balloon catheters can establish conformal contact with curved tissue surfaces, support high-density spatiotemporal mapping of temperature, pressure and electrophysiological parameters and allow for programmable electrical stimulation, radiofrequency ablation and irreversible electroporation. Integrating multimodal and multiplexing capabilities into minimally invasive surgical instruments may improve surgical performance and patient outcomes.

N-doped graphene nanoribbons as efficient metal-free counter electrodes for disulfide/thiolate redox mediated DSSCs.

Nitrogen-doped graphene nanoribbons (N-GNRs) were prepared by thermal treatment of the as-zipped graphene oxide nanoribbons in NH3 gas. X-ray photoelectron spectroscopy (XPS) measurements revealed a high nitrogen content up to 6.5 atom% for the as-prepared N-GNRs. This, together with the high Brunauer-Emmett-Teller (BET) surface area of about 751 cm(2) g(-1), prompted us to use the N-GNR as the first low-cost, metal-free counter electrode for disulfide/thiolate redox mediated dye-sensitized solar cells (DSSCs). Compared with the widely-used platinum electrode, the newly-developed N-GNR counter electrode showed a dramatically improved power conversion efficiency for DSSCs based on the thiolate/disulfide redox shuttle. The observed superior cell performance was attributed to the enhanced charge transfer capability and electrocatalytic activity induced by N-doping of the graphene nanoribbon.