Flexible, Miniaturized Sensing Probes Inspired by Biofuel Cells for Monitoring Synaptically Released Glutamate in the Mouse Brain.

Chemical biomarkers in the central nervous system can provide valuable quantitative measures to gain insight into the etiology and pathogenesis of neurological diseases. Glutamate, one of the most important excitatory neurotransmitters in the brain, has been found to be upregulated in various neurological disorders, such as traumatic brain injury, Alzheimer's disease, stroke, epilepsy, chronic pain, and migraines. However, quantitatively monitoring glutamate release in situ has been challenging. This work presents a novel class of flexible, miniaturized probes inspired by biofuel cells for monitoring synaptically released glutamate in the nervous system. The resulting sensors, with dimensions as low as 50 by 50 µm, can detect real-time changes in glutamate within the biologically relevant concentration range. Experiments exploiting the hippocampal circuit in mice models demonstrate the capability of the sensors in monitoring glutamate release via electrical stimulation using acute brain slices. These advances could aid in basic neuroscience studies and translational engineering, as the sensors provide a diagnostic tool for neurological disorders. Additionally, adapting the biofuel cell design to other neurotransmitters can potentially enable the detailed study of the effect of neurotransmitter dysregulation on neuronal cell signaling pathways and revolutionize neuroscience.

A "Two-Part" Resonance Circuit Based Detachable Sweat Patch for Noninvasive Biochemical and Biophysical Sensing.

Wearable electronics play important roles in noninvasive, continuous, and personalized monitoring of multiple biosignals generated by the body. To unleash their full potential for next-generation human centered bio-integrated electronics, the wireless sensing capability is a desirable feature. However, state-of-the-art wireless sensing technologies exploit rigid and bulky electronic modules for power supply, signal generation, and data transmission. This study reports a battery-free device technology based on a "two-part" resonance circuit model with modularized, physically separated, and detachable functional units for magnetic coupling and biosensing. The resulting platform combines advantages of electronics and microfluidics with low cost, minimized form factors, and improved performance stability. Demonstration of a detachable sweat patch capable of simultaneous recording of cortisol concentration, pH value, and temperature highlights the potential of the "two-part" circuit for advanced, transformative biosensing. The resulting wireless sensors provide a new engineering solution to monitoring biosignals through intimate and seamless integration with skin surfaces.

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

A Wireless, Regeneratable Cocaine Sensing Scheme Enabled by Allosteric Regulation of pH Sensitive Aptamers.

A key challenge for achieving continuous biosensing with existing technologies is the poor reusability of the biorecognition interface due to the difficulty in the dissociation of analytes from the bioreceptors upon surface saturation. In this work, we introduce a regeneratable biosensing scheme enabled by allosteric regulation of a re-engineered pH sensitive anti-cocaine aptamer. The aptamer can regain its affinity with target analytes due to proton-promoted duplex-to-triplex transition in DNA configuration followed by the release of adsorbed analytes. A Pd/PdHx electrode placed next to the sensor can enable the pH regulation of the local chemical environment via electrochemical reactions. Demonstration of a "flower-shaped", stretchable, and inductively coupled electronic system with sensing and energy harvesting capabilities provides a promising route to designing wireless devices in biointegrated forms. These advances have the potential for future development of electronic sensing platforms with on-chip regeneration capability for continuous, quantitative, and real-time monitoring of chemical and biological markers.

High-speed, scanned laser structuring of multi-layered eco/bioresorbable materials for advanced electronic systems.

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.

A dynamically reprogrammable surface with self-evolving shape morphing.

Dynamic shape-morphing soft materials systems are ubiquitous in living organisms; they are also of rapidly increasing relevance to emerging technologies in soft machines1-3, flexible electronics4,5 and smart medicines6. Soft matter equipped with responsive components can switch between designed shapes or structures, but cannot support the types of dynamic morphing capabilities needed to reproduce natural, continuous processes of interest for many applications7-24. Challenges lie in the development of schemes to reprogram target shapes after fabrication, especially when complexities associated with the operating physics and disturbances from the environment can stop the use of deterministic theoretical models to guide inverse design and control strategies25-30. Here we present a mechanical metasurface constructed from a matrix of filamentary metal traces, driven by reprogrammable, distributed Lorentz forces that follow from the passage of electrical currents in the presence of a static magnetic field. The resulting system demonstrates complex, dynamic morphing capabilities with response times within 0.1 second. Implementing an in situ stereo-imaging feedback strategy with a digitally controlled actuation scheme guided by an optimization algorithm yields surfaces that can follow a self-evolving inverse design to morph into a wide range of three-dimensional target shapes with high precision, including an ability to morph against extrinsic or intrinsic perturbations. These concepts support a data-driven approach to the design of dynamic soft matter, with many unique characteristics.

Battery-free, tuning circuit-inspired wireless sensor systems for detection of multiple biomarkers in bodily fluids.

Tracking the concentration of biomarkers in biofluids can provide crucial information about health status. However, the complexity and nonideal form factors of conventional digital wireless schemes impose challenges in realizing biointegrated, lightweight, and miniaturized sensors. Inspired by the working principle of tuning circuits in radio frequency electronics, this study reports a class of battery-free wireless biochemical sensors: In a resonance circuit, the coupling between a sensing interface and an inductor-capacitor oscillator through a pair of varactor diodes converts a change in electric potential into a modulation in capacitance, resulting in a quantifiable shift of the resonance circuit. Proper design of sensing interfaces with biorecognition elements enables the detection of various biomarkers, including ions, neurotransmitters, and metabolites. Demonstrations of "smart accessories" and miniaturized probes suggest the broad utility of this circuit model. The design concepts and sensing strategies provide a realistic pathway to building biointegrated electronics for wireless biochemical sensing.

Mechanically Guided Hierarchical Assembly of 3D Mesostructures.

3D, hierarchical micro/nanostructures formed with advanced functional materials are of growing interest due to their broad potential utility in electronics, robotics, battery technology, and biomedical engineering. Among various strategies in 3D micro/nanofabrication, a set of methods based on compressive buckling offers wide-ranging material compatibility, fabrication scalability, and precise process control. Previously reports on this type of approach rely on a single, planar prestretched elastomeric platform to transform thin-film precursors with 2D layouts into 3D architectures. The simple planar configuration of bonding sites between these precursors and their assembly substrates prevents the realization of certain types of complex 3D geometries. In this paper, a set of hierarchical assembly concepts is reported that leverage multiple layers of prestretched elastomeric substrates to induce not only compressive buckling of 2D precursors bonded to them but also of themselves, thereby creating 3D mesostructures mounted at multiple levels of 3D frameworks with complex, elaborate configurations. Control over strains used in these processes provides reversible access to multiple different 3D layouts in a given structure. Examples to demonstrate these ideas through both experimental and computational results span vertically aligned helices to closed 3D cages, selected for their relevance to 3D conformal bio-interfaces and multifunctional microsystems.

Materials and Interface Designs of Waterproof Field-Effect Transistor Arrays for Detection of Neurological Biomarkers.

The continuous, real-time, and concurrent detection of multiple biomarkers in bodily fluids is of high significance for advanced healthcare. While active, semiconductor-based biochemical sensing platforms provide levels of functionality exceeding those of their conventional passive counterparts, the stability of the active biosensors in the liquid environment for continuous operation remains a challenging topic. This work reports the development of a class of flexible and waterproof field-effect transistor arrays for multiplexed biochemical sensing. In this design, monolithic, ultrathin, dense, and low defect nanomembranes consisting of monocrystalline Si and thermally grown SiO2 simultaneously serve as high-performance backplane electronics for signal transduction and stable biofluid barriers with high structural integrity due to the high formation temperature. Coupling the waterproof transistors with various ion-selective membranes through the gate electrode allows for sensitive and selective detection of multiple ions as biomarkers for traumatic brain injury. The study also demonstrates a similar encapsulation structure which enables the design of waterproof amperometric sensors based on this materials strategy and integration scheme. Overall, key advantages in flexibility, stability, and multifunctionality highlight the potential of using such electronic sensing platforms for concurrent, continuous detection of various neurological biomarkers, proving a promising approach for early diagnosis and intervention of chronic diseases.

Waterproof, flexible field-effect transistors with submicron monocrystalline Si nanomembrane derived encapsulation for continuous pH sensing.

To understand the physio-pathological state of patients suffering from chronic diseases, scientists and clinicians need sensors to track chemical signals in real-time. However, the lack of stable, safe, and scalable biochemical sensing platforms capable of continuous operation in liquid environments imposes significant challenges in the timely diagnosis, intervention, and treatment of chronic conditions. This work reports a novel strategy for fabricating waterproof and flexible biochemical sensors with active electronic components, which feature a submicron encapsulation layer derived from monocrystalline Si nanomembranes with a high structural integrity due to the high formation temperature (>1000 °C). The ultrathin, yet dense and low-defect encapsulation enables continuous operation of field-effect transistors in biofluids for chemical sensing. The excellent stability in liquid environment and pH sensing performance of such transistors suggest their great potential as the foundation of waterproof and scalable biochemical sensors with active functionalities in the future. The understandings, knowledge base, and demonstrations for pH sensing reported here set the stage for the next generation long-term biosensing with a broad applicability in biomedical research, food science, and advanced healthcare.

Complex 3D microfluidic architectures formed by mechanically guided compressive buckling.

Microfluidic technologies have wide-ranging applications in chemical analysis systems, drug delivery platforms, and artificial vascular networks. This latter area is particularly relevant to 3D cell cultures, engineered tissues, and artificial organs, where volumetric capabilities in fluid distribution are essential. Existing schemes for fabricating 3D microfluidic structures are constrained in realizing desired layout designs, producing physiologically relevant microvascular structures, and/or integrating active electronic/optoelectronic/microelectromechanical components for sensing and actuation. This paper presents a guided assembly approach that bypasses these limitations to yield complex 3D microvascular structures from 2D precursors that exploit the full sophistication of 2D fabrication methods. The capabilities extend to feature sizes <5 µm, in extended arrays and with various embedded sensors and actuators, across wide ranges of overall dimensions, in a parallel, high-throughput process. Examples include 3D microvascular networks with sophisticated layouts, deterministically designed and constructed to expand the geometries and operating features of artificial vascular networks.

Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

Transient Light-Emitting Diodes Constructed from Semiconductors and Transparent Conductors that Biodegrade Under Physiological Conditions.

Transient forms of electronics, systems that disintegrate, dissolve, resorb, or sublime in a controlled manner after a well-defined operating lifetime, are of interest for applications in hardware secure technologies, temporary biomedical implants, "green" consumer devices and other areas that cannot be addressed with conventional approaches. Broad sets of materials now exist for a range of transient electronic components, including transistors, diodes, antennas, sensors, and even batteries. This work reports the first examples of transient light-emitting diodes (LEDs) that can completely dissolve in aqueous solutions to biologically and environmentally benign end products. Thin films of highly textured ZnO and polycrystalline Mo serve as semiconductors for light generation and conductors for transparent electrodes, respectively. The emitted light spans a range of visible wavelengths, where nanomembranes of monocrystalline silicon can serve as transient filters to yield red, green, and blue LEDs. Detailed characterization of the material chemistries and morphologies of the constituent layers, assessments of their performance properties, and studies of their dissolution processes define the underlying aspects. These results establish an electroluminescent light source technology for unique classes of optoelectronic systems that vanish into benign forms when exposed to aqueous conditions in the environment or in living organisms.