Reem M. Almasri

Brain/computer interfaces (BCIs) rely on the concurrent recording of many channels of electrical activity from excitable tissue. Traditionally such neural interfacing has been performed using cumbersome, channel-limited multielectrode arrays. We believe that BCIs can greatly benefit from using an optical approach based on simple yet powerful liquid-crystal based transducer technology. This approach potentially offers a technology platform that can sustain the necessary bandwidth, density of channels, responsivity, and conformability that are required for the long-term viability of such interfaces. In this paper we review the overall architecture of this approach, the challenges it faces, and the solutions that are being developed at UNSW Sydney.

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.

The design of a bi-directional optical-electrode or ‘optrode’ for peripheral nerve and brain-machine interfacing is proposed and its principle of operation detailed, which is able to provide biphasic stimulus and charge balancing functionalities. The prototype chip is fabricated, characterised on the bench, and assessed in vivo and ex vivo . Results show that it can simultaneously stimulate and record from the rabbit sciatic nerve, and entrainment of the sino-atrial node is achieved and observed by the prototype. Then, a discrete component circuit is tested for validation of this charge-balancing effect. Experimental results from in vivo testing on rabbit sciatic nerves demonstrate that the voltage generated by photodiodes at around 0.5 to 0.6V is able to evoke compound action potentials, and the activated light-dependent resistor removed more than 80% of the post-stimulus charge stored at the interface.

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.

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 µ m 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.

Neural interfaces are the part of the neural prosthesis that is 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 tis-sue 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) polycaprolac-tone (PCL), a bioresorbable polyester with outstanding mechanical properties. Electrodes for neural recording were built at 30, 50, 75, 100 µm diameter using AgNPs/(3,4- ethylenedioxytiophene)-poly(styrenesulfonate) (AgNPs/PEDOT:PSS), which through our process achieved the lowest impedance reported in literature reaching ∼200 Ω at 1 kHz for a 50 µm elec-trode 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 rec-ord single-unit activity were confirmed by in-vitro tests on both rat PC12 cells and isolated neural rat retina, respectively.