Emerging trends in the development of flexible optrode arrays for electrophysiology.

Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue-device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems.

Liquid crystal electro-optical transducers for electrophysiology sensing applications.

Objective.Biomedical instrumentation and clinical systems for electrophysiology rely on electrodes and wires for sensing and transmission of bioelectric signals. However, this electronic approach constrains bandwidth, signal conditioning circuit designs, and the number of channels in invasive or miniature devices. This paper demonstrates an alternative approach using light to sense and transmit the electrophysiological signals.Approach.We develop a sensing, passive, fluorophore-free optrode based on the birefringence property of liquid crystals (LCs) operating at the microscale.Main results.We show that these optrodes can have the appropriate linearity (µ± s.d.: 99.4 ± 0.5%,n = 11 devices), relative responsivity (µ± s.d.: 57 ± 12%V-1,n = 5 devices), and bandwidth (µ± s.d.: 11.1 ± 0.7 kHz,n = 7 devices) for transducing electrophysiology signals into the optical domain. We report capture of rabbit cardiac sinoatrial electrograms and stimulus-evoked compound action potentials from the rabbit sciatic nerve. We also demonstrate miniaturisation potential by fabricating multi-optrode arrays, by developing a process that automatically matches each transducer element area with that of its corresponding biological interface.Significance.Our method of employing LCs to convert bioelectric signals into the optical domain will pave the way for the deployment of high-bandwidth optical telecommunications techniques in ultra-miniature clinical diagnostic and research laboratory neural and cardiac interfaces.

Electromechanical Stability and Transmission Behavior of Transparent Conductive Films for Biomedical Optoelectronic Devices.

The application of transparent conductive films to flexible biomedical optoelectronics is limited by stringent requirements on the candidate materials' electromechanical and optical properties as well as their biological performance. Thin films of graphene and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) are sought as mechanically flexible alternatives to traditional indium tin oxide (ITO). However, they require more understanding of their suitability for biomedical optoelectronic devices in terms of transmission behavior and electromechanical stability. This study shows that the relative increase in sheet resistance under cyclic loading for ITO, graphene, and PEDOT:PSS was 3546±3908%,12±2.7%, and 62±68%, respectively. Moreover, graphene and PEDOT:PSS showed a transmission uniformity of 9.3% and 36.3% (380-2000 nm), respectively, compared with ITO film (61%). Understanding the optical, electrical, and mechanical limits of the transparent conductive films facilitates the optimization of flexible optoelectronic designs to fit multiple biomedical research and clinical applications.

Impedance Properties of Multi-Optrode Biopotential Sensing Arrays.

Recording and monitoring electrically-excitable cells is critical to understanding the complex cellular networking within organs as well as the processes underlying many electro-physiological pathologies. Biopotential recording using an optical-electrode (optrode) is a novel approach which has potential to significantly improve interface-instrumentation impedance mismatching as recording contact-sizes become smaller and smaller. Optrodes incorporate a conductive interface that can sense extracellular potential and an underlying layer of liquid crystals that passively transduces electrical signals into measurable optical signals. This study investigates the impedance properties of this optical technology by varying the diameter of recording sites and observing the corresponding changes in the impedance values. The results show that the liquid crystals in this optrode platform exhibit input impedance values (1 MΩ - 100 GΩ) that are three orders of magnitude higher than the corresponding interface impedance, which is appropriate for voltage sensing. The automatic scaling of the input impedance enabled within the optrode system maintains a relatively constant ratio between input and total system impedance of about one for sensing areas with diameters ranging from 40 µm to 1 mm, at which the calculated signal loss is predicted to be <1%. This feature preserves the interface-transducer impedance ratio, regardless of the size of the recording site, allowing development of passive optrode arrays capable of very high spatial-resolution recordings.

Highly Flexible Single-Unit Resolution All Printed Neural Interface on a Bioresorbable Backbone.

Neural interfaces are the parts of the neural prosthesis that are in contact with the target tissue. The mechanical, chemical, and electrical properties of these interfaces can be a major determinant of the life of the implant and the neural tissue for chronic and even acute integrations. In this work, we developed a fully inkjet-printed, flexible neural interface on a bioresorbable backbone capable of recording high-fidelity neural activity. We utilized room temperature fabrication processes that overcome the limitations of semiconductor fabrication techniques for processing low-melting point polymers while maintaining high spatial and single-cell recording resolution. The ∼8 µm-thick devices in this study were fabricated onto two flexible polymers: (a) polyimide (PI), a biocompatible polymer commonly used for neural interfaces, and (b) polycaprolactone (PCL), a bioresorbable polyester with outstanding mechanical properties. Electrodes for neural recording were built at 30, 50, 75, and 100 µm diameter using silver nanoparticles/(3,4-ethylenedioxytiophene)-poly(styrenesulfonate) (AgNPs/PEDOT:PSS), which through our process achieved the lowest impedance reported in the literature reaching ∼200 Ω at 1 kHz for a 50 µm electrode diameter. We further enhanced the electrochemical performance of AgNPs/PEDOT:PSS by an order of magnitude by incorporating exfoliated graphene into the electrodes. The biocompatibility of the fabricated devices and their ability to record single-unit activity were confirmed by in vitro tests on both rat PC12 cells and isolated neural rat retina, respectively.