Multiplexed neurochemical sensing with sub-nM sensitivity across 2.25 mm2 area.

Multichannel arrays capable of real-time sensing of neuromodulators in the brain are crucial for gaining insights into new aspects of neural communication. However, measuring neurochemicals, such as dopamine, at low concentrations over large areas has proven challenging. In this research, we demonstrate a novel approach that leverages the scalability and processing power offered by microelectrode array devices integrated with a functionalized, high-density microwire bundle, enabling electrochemical sensing at an unprecedented scale and spatial resolution. The sensors demonstrate outstanding selective molecular recognition by incorporating a selective polymeric membrane. By combining cutting-edge commercial multiplexing, digitization, and data acquisition hardware with a bio-compatible and highly sensitive neurochemical interface array, we establish a powerful platform for neurochemical analysis. This multichannel array has been successfully utilized in vitro and ex vivo systems. Notably, our results show a sensing area of 2.25 mm2 with an impressive detection limit of 820 pM for dopamine. This new approach paves the way for investigating complex neurochemical processes and holds promise for advancing our understanding of brain function and neurological disorders.

Direct electron beam patterning of electro-optically active PEDOT:PSS.

The optical and electronic tunability of the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has enabled emerging applications as diverse as bioelectronics, flexible electronics, and micro- and nano-photonics. High-resolution spatial patterning of PEDOT:PSS opens up opportunities for novel active devices in a range of fields. However, typical lithographic processes require tedious indirect patterning and dry etch processes, while solution-processing methods such as ink-jet printing have limited spatial resolution. Here, we report a method for direct write nano-patterning of commercially available PEDOT:PSS through electron-beam induced solubility modulation. The written structures are water stable and maintain the conductivity as well as electrochemical and optical properties of PEDOT:PSS, highlighting the broad utility of our method. We demonstrate the potential of our strategy by preparing prototypical nano-wire structures with feature sizes down to 250 nm, an order of magnitude finer than previously reported direct write methods, opening the possibility of writing chip-scale microelectronic and optical devices. We finally use the high-resolution writing capabilities to fabricate electrically-switchable optical diffraction gratings. We show active switching in this archetypal system with >95 % contrast at CMOS-compatible voltages of +2 V and -3 V, offering a route towards highly-miniaturized dynamic optoelectronic devices.

A CMOS-based highly scalable flexible neural electrode interface.

Perception, thoughts, and actions are encoded by the coordinated activity of large neuronal populations spread over large areas. However, existing electrophysiological devices are limited by their scalability in capturing this cortex-wide activity. Here, we developed an electrode connector based on an ultra-conformable thin-film electrode array that self-assembles onto silicon microelectrode arrays enabling multithousand channel counts at a millimeter scale. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed Flex2Chip. Capillary-assisted assembly drives the pads to deform toward the chip surface, and van der Waals forces maintain this deformation, establishing Ohmic contact. Flex2Chip arrays successfully measured extracellular action potentials ex vivo and resolved micrometer scale seizure propagation trajectories in epileptic mice. We find that seizure dynamics in absence epilepsy in the Scn8a+/- model do not have constant propagation trajectories.

On-Demand, Reversible, Ultrasensitive Polymer Membrane Based on Molecular Imprinting Polymer.

The development of in vivo, longitudinal, real-time monitoring devices is an essential step toward continuous, precision health monitoring. Molecularly imprinted polymers (MIPs) are popular sensor capture agents that are more robust than antibodies and have been used for sensors, drug delivery, affinity separations, assays, and solid-phase extraction. However, MIP sensors are typically limited to one-time use due to their high binding affinity (>107 M-1) and slow-release kinetics (<10-4 µM/sec). To overcome this challenge, current research has focused on stimuli-responsive MIPs (SR-MIPs), which undergo a conformational change induced by external stimuli to reverse molecular binding, requiring additional chemicals or outside stimuli. Here, we demonstrate fully reversible MIP sensors based on electrostatic repulsion. Once the target analyte is bound within a thin film MIP on an electrode, a small electrical potential successfully releases the bound molecules, enabling repeated, accurate measurements. We demonstrate an electrostatically refreshed dopamine sensor with a 760 pM limit of detection, linear response profile, and accuracy even after 30 sensing-release cycles. These sensors could repeatedly detect <1 nM dopamine released from PC-12 cells in vitro, demonstrating they can longitudinally measure low concentrations in complex biological environments without clogging. Our work provides a simple and effective strategy for enhancing the use of MIPs-based biosensors for all charged molecules in continuous, real-time health monitoring and other sensing applications.

An integrated perspective for the diagnosis and therapy of neurodevelopmental disorders - From an engineering point of view.

Neurodevelopmental disorders (NDDs) are complex conditions with largely unknown pathophysiology. While many NDD symptoms are familiar, the cause of these disorders remains unclear and may involve a combination of genetic, biological, psychosocial, and environmental risk factors. Current diagnosis relies heavily on behaviorally defined criteria, which may be biased by the clinical team's professional and cultural expectations, thus a push for new biological-based biomarkers for NDDs diagnosis is underway. Emerging new research technologies offer an unprecedented view into the electrical, chemical, and physiological activity in the brain and with further development in humans may provide clinically relevant diagnoses. These could also be extended to new treatment options, which can start to address the underlying physiological issues. When combined with current speech, language, occupational therapy, and pharmacological treatment these could greatly improve patient outcomes. The current review will discuss the latest technologies that are being used or may be used for NDDs diagnosis and treatment. The aim is to provide an inspiring and forward-looking view for future research in the field.