A low-power stretchable neuromorphic nerve with proprioceptive feedback.

By relaying neural signals from the motor cortex to muscles, devices for neurorehabilitation can enhance the movement of limbs in which nerves have been damaged as a consequence of injuries affecting the spinal cord or the lower motor neurons. However, conventional neuroprosthetic devices are rigid and power-hungry. Here we report a stretchable neuromorphic implant that restores coordinated and smooth motions in the legs of mice with neurological motor disorders, enabling the animals to kick a ball, walk or run. The neuromorphic implant acts as an artificial efferent nerve by generating electrophysiological signals from excitatory post-synaptic signals and by providing proprioceptive feedback. The device operates at low power (~1/150 that of a typical microprocessor system), and consists of hydrogel electrodes connected to a stretchable transistor incorporating an organic semiconducting nanowire (acting as an artificial synapse), connected via an ion gel to an artificial proprioceptor incorporating a carbon nanotube strain sensor (acting as an artificial muscle spindle). Stretchable electronics with proprioceptive feedback may inspire the further development of advanced neuromorphic devices for neurorehabilitation.

Low-Cost Graphene-Based Digital Microfluidic System.

In this work, the laser-scribing technique was used as a low-cost, rapid and facile method for fabricating digital microfluidic (DMF) systems. Laser-scribed graphene (LSG) electrodes are directly synthesized on flexible substrates to pattern the DMF electrode arrays. This facilitates the DMF electrodes' fabrication process by eliminating many microfabrication steps. An electrowetting test was performed to investigate the effectiveness of the LSG DMF electrodes in changing the contact angles of droplets. Different DMF operations were successfully performed using the proposed LSG DMF chips in both open and closed DMF systems. The quality and output resolution were examined to assess the performance of such patterned electrodes in the DMF systems. To verify the efficacy of the LSG DMF chips, a one-step direct assay for the detection of Legionellapneumophila deoxyribonucleic acid (DNA) was performed on the chip without the need for any washing step. The high specificity in distinguishing a single-nucleotide mismatch was achieved by detecting target DNA concentrations as low as 1 nM. Our findings suggest that the proposed rapid and easy fabrication method for LSG DMF electrodes offers a great platform for low-cost and easily accessible point-of-care diagnostic devices.

Effects of Water and Different Solutes on Carbon-Nanotube Low-Voltage Field-Effect Transistors.

Semiconducting single-walled carbon nanotubes (swCNTs) are a promising class of materials for emerging applications. In particular, they are demonstrated to possess excellent biosensing capabilities, and are poised to address existing challenges in sensor reliability, sensitivity, and selectivity. This work focuses on swCNT field-effect transistors (FETs) employing rubbery double-layer capacitive dielectric poly(vinylidene fluoride-co-hexafluoropropylene). These devices exhibit small device-to-device variation as well as high current output at low voltages (<0.5 V), making them compatible with most physiological liquids. Using this platform, the swCNT devices are directly exposed to aqueous solutions containing different solutes to characterize their effects on FET current-voltage (FET I-V) characteristics. Clear deviation from ideal characteristics is observed when swCNTs are directly contacted by water. Such changes are attributed to strong interactions between water molecules and sp2 -hybridized carbon structures. Selective response to Hg2+ is discussed along with reversible pH effect using two distinct device geometries. Additionally, the influence of aqueous ammonium/ammonia in direct contact with the swCNTs is investigated. Understanding the FET I-V characteristics of low-voltage swCNT FETs may provide insights for future development of stable, reliable, and selective biosensor systems.

Soft and elastic hydrogel-based microelectronics for localized low-voltage neuromodulation.

Narrowing the mechanical mismatch between tissue and implantable microelectronics is essential for reducing immune responses and for accommodating body movement. However, the design of implantable soft electronics (on the order of 10 kPa in modulus) remains a challenge because of the limited availability of suitable electronic materials. Here, we report electrically conductive hydrogel-based elastic microelectronics with Young's modulus values in the kilopascal range. The system consists of a highly conductive soft hydrogel as a conductor and an elastic fluorinated photoresist as the passivation insulation layer. Owing to the high volumetric capacitance and the passivation layer of the hydrogel, electrode arrays of the thin-film hydrogel 'elastronics', 20 µm in feature size, show a significantly reduced interfacial impedance with tissue, a current-injection density that is ~30 times higher than that of platinum electrodes, and stable electrical performance under strain. We demonstrate the use of the soft elastronic arrays for localized low-voltage electrical stimulation of the sciatic nerve in live mice.

A Dual-Crosslinking Design for Resilient Lithium-Ion Conductors.

Solid-state electrolyte materials are attractive options for meeting the safety and performance needs of advanced lithium-based rechargeable battery technologies because of their improved mechanical and thermal stability compared to liquid electrolytes. However, there is typically a tradeoff between mechanical and electrochemical performance. Here an elastic Li-ion conductor with dual covalent and dynamic hydrogen bonding crosslinks is described to provide high mechanical resilience without sacrificing the room-temperature ionic conductivity. A solid-state lithium-metal/LiFePO4 cell with this resilient electrolyte can operate at room temperature with a high cathode capacity of 152 mAh g-1 for 300 cycles and can maintain operation even after being subjected to intense mechanical impact testing. This new dual crosslinking design provides robust mechanical properties while maintaining ionic conductivity similar to state-of-the-art polymer-based electrolytes. This approach opens a route toward stable, high-performance operation of solid-state batteries even under extreme abuse.

A bioinspired flexible organic artificial afferent nerve.

The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.

Skin electronics from scalable fabrication of an intrinsically stretchable transistor array.

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.

Rapid and specific SPRi detection of L. pneumophila in complex environmental water samples.

Legionellosis is a very devastating disease worldwide mainly due to unpredictable outbreaks in man-made water systems. Developing a highly specific and sensitive rapid detection system that detects only metabolically active bacteria is a main priority for water quality assessment. We previously developed a versatile technique for sensitive and specific detection of synthetic RNA. In the present work, we further investigated the performance of the developed biosensor for detection of Legionella pneumophila in complex environmental samples, particularly those containing protozoa. The specificity and sensitivity of the detection system were verified using total RNA extracted from L. pneumophila in spiked water co-cultured with amoebae. We demonstrated that the expression level of ribosomal RNA (rRNA) is extremely dependent on the environmental conditions. The presence of amoebae with L. pneumophila, especially in nutrition-deprived samples, increased the amount of L. pneumophila 15-fold after 1 week as measured through the expression of 16s rRNA. Using the developed surface plasmon resonance imaging (SPRi) detection method, we were also able to successfully detect L. pneumophila within 3 h, both in the presence and absence of amoebae in the complex environmental samples obtained from a cooling water tower. These findings suggest that the developed biosensing system is a viable method for rapid, real-time and effective detection not only for L. pneumophila in environmental samples but also to assess the risk associated with the use of water contaminated with other pathogens.

Rapid and multiplex detection of Legionella's RNA using digital microfluidics.

Despite recent advances in the miniaturization and automation of biosensors, technologies for on-site monitoring of environmental water are still at an early stage of development. Prevention of outbreaks caused by pathogens such as Legionella pneumophila would be facilitated by the development of sensitive and specific bioanalytical assays that can be easily integrated in miniaturized fluidic handling systems. In this work, we report on the integration of an amplification-free assay in digital microfluidics (DMF) for the detection of Legionella bacteria based on targeting 16s rRNA. We first review the design of the developed DMF devices, which provide the capability to store up to one hundred nL-size droplets simultaneously, and discuss the challenges involved with on-chip integration of the RNA-based assay. By optimizing the various steps of the assay, including magnetic capture, hybridization duration, washing steps, and assay temperature, a limit of detection as low as 1.8 attomoles of synthetic 16s rRNA was obtained, which compares advantageously to other amplification-free detection systems. Finally, we demonstrate the specificity of the developed assay by performing multiplex detection of 16s rRNAs from a pathogenic and a non-pathogenic species of Legionella. We believe the developed DMF devices combined with the proposed detection system offers new prospects for the deployment of rapid and cost-effective technologies for on-site monitoring of pathogenic bacteria.

Design and analysis of a spectro-angular surface plasmon resonance biosensor operating in the visible spectrum.

Surface plasmon resonance (SPR) sensing is one of the most widely used methods to implement biosensing due to its sensitivity and capacity for label-free detection. Whilst most commercial SPR sensors operate in the angular regime, it has recently been shown that an increase in sensitivity and a greater robustness against noise can be achieved by measuring the reflectivity when varying both the angle and wavelength simultaneously, in a so-called spectro-angular SPR biosensor. A single value decomposition method is used to project the two-dimensional spectro-angular reflection signal onto a basis set and allow the image obtained from an unknown refractive index sample to be compared very accurately with a pre-calculated reference set. Herein we demonstrate that a previously reported system operated in the near infra-red has a lower detection limit when operating in the visible spectrum due to the improved spatial resolution and numerical precision of the image sensor. The SPR biosensor presented here has an experimental detection limit of 9.8 × 10(-7) refractive index unit. To validate the system as a biosensor, we also performed the detection of synthetic RNA from pathogenic Legionella pneumophila with the developed biosensing platform.

Sub-femtomole detection of 16s rRNA from Legionella pneumophila using surface plasmon resonance imaging.

Legionellosis has been and continues to be a life-threatening disease worldwide, even in developed countries. Given the severity and unpredictability of Legionellosis outbreaks, developing a rapid, highly specific, and sensitive detection method is thus of great pertinence. In this paper, we demonstrate that sub-femtomole levels of 16s rRNA from pathogenic Legionella pneumophila can be timely and effectively detected using an appropriate designed capture, detector probes, and a QD SPRi signal amplification strategy. To achieve specific and sensitive detection, optimal hybridization conditions and parameters were implemented. Among these parameters, fragmentation of the 16s rRNA and further signal amplification by QDs were found to be the main parameters contributing to signal enhancement. The appropriate design of the detector probes also increased the sensitivity of the detection system, mainly due to secondary structure of 16s rRNA. The use of 16s rRNA from L. pneumophila allowed for the detection of metabolically active pathogens with high sensitivity. Detection of 16s rRNA in solutions as diluted as 1 pM at 450 µL (0.45 femtomole) was achieved in less than 3h, making our approach suitable for the direct, timely, and effective detection of L. pneumophila within man-made water systems.

Microfluidic designs and techniques using lab-on-a-chip devices for pathogen detection for point-of-care diagnostics.

Effective pathogen detection is an essential prerequisite for the prevention and treatment of infectious diseases. Despite recent advances in biosensors, infectious diseases remain a major cause of illnesses and mortality throughout the world. For instance in developing countries, infectious diseases account for over half of the mortality rate. Pathogen detection platforms provide a fundamental tool in different fields including clinical diagnostics, pathology, drug discovery, clinical research, disease outbreaks, and food safety. Microfluidic lab-on-a-chip (LOC) devices offer many advantages for pathogen detection such as miniaturization, small sample volume, portability, rapid detection time and point-of-care diagnosis. This review paper outlines recent microfluidic based devices and LOC design strategies for pathogen detection with the main focus on the integration of different techniques that led to the development of sample-to-result devices. Several examples of recently developed devices are presented along with respective advantages and limitations of each design. Progresses made in biomarkers, sample preparation, amplification and fluid handling techniques using microfluidic platforms are also covered and strategies for multiplexing and high-throughput analysis, as well as point-of-care diagnosis, are discussed.

Patterning multiplex protein microarrays in a single microfluidic channel.

The development of versatile biofunctional surfaces is a fundamental prerequisite in designing Lab on a Chip (LOC) devices for applications in biosensing interfaces and microbioreactors. The current paper presents a rapid combinatorial approach to create multiplex protein patterns in a single microfluidic channel. This approach consists of coupling microcontact printing with microfluidic patterning, where microcontact printing is employed for silanization using (3-Aminopropyl) triethoxysilane (APTES), followed by microfluidic patterning of multiple antibodies. As a result, the biomolecules of choice could be covalently attached to the microchannel surface, thus creating a durable and highly resistant functional interface. Moreover, the experimental procedure was designed to create a microfluidic platform that maintains functionality at high flow rates. The functionalized surfaces were characterized using X-ray photoelectron spectroscopy (XPS) and monitored with fluorescence microscopy at each step of functionalization. To illustrate the possibility of patterning multiple biomolecules along the cross section of a single microfluidic channel, microarrays of five different primary antibodies were patterned onto a single channel and their functionality was evaluated accordingly through a multiplex immunoassay using secondary antibodies specific to each patterned primary antibody. The resulting patterns remained stable at shear stresses of up to 50 dyn/cm(2). The overall findings suggest that the developed multiplex functional interface on a single channel can successfully lead to highly resistant multiplex functional surfaces for high throughput biological assays.

Benchtop fabrication of PDMS microstructures by an unconventional photolithographic method.

Poly(dimethylsiloxane) (PDMS) microstructures have been widely used in bio-microelectromechanical systems (bio-MEMS) for various types of analytical, diagnostic and therapeutic applications. However, PDMS-based soft lithographic techniques still use conventional microfabrication processes to generate a master mold, which requires access to clean room facilities and costly equipment. With the increasing use of these systems in various fields, the development of benchtop systems for fabricating microdevices is emerging as an important challenge in their widespread use. Here we demonstrate a simple, low-cost and rapid method to fabricate PDMS microstructures by using micropatterned poly(ethylene glycol) diacrylate (PEGDA) master molds. In this method, PEGDA microstructures were patterned on a glass substrate by photolithography under ambient conditions and by using simple tools. The resulting PEGDA structures were subsequently used to generate PDMS microstructures by standard molding in a reproducible and repeatable manner. The thickness of the PEGDA microstructures was controllable from 15 to 300 µm by using commonly available spacer materials. We also demonstrate the use of this method to fabricate microfluidic channels capable of generating concentration gradients. In addition, we fabricated PEGDA microstructures by photolithography from the light generated from commonly available laminar cell culture hood. These data suggest that this approach could be beneficial for fabricating low-cost PDMS-based microdevices in resource limited settings.