This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The fabrication process combines traditional silicon thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. Direct laser-writing of 3D-printed electrodes has been described before, but this report is the first to provide a method for producing high-aspect-ratio structures. One prototype, a 16-channel array with 300 µm pitch, demonstrates successful electrophysiological signal capture from bird and mouse brains. Additional devices include 90 µm pitch arrays, biomimetic mosquito needles that penetrate through the dura of birds, and porous electrodes with enhanced surface area. The rapid 3D printing and wafer-scale methods described here will enable efficient device fabrication and new studies examining the relationship between electrode geometry and electrode performance. Applications include small animal models, nerve interfaces, retinal implants, and other devices requiring compact, high-density 3D electrodes.
As additional physiological functions of hydrogen sulfide (H2S) are discovered, developing practical methods for exogenous H2S delivery is important. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) functionalized with H2S-releasing anethole dithiolethione (ADT-OH) through ester bonds are being investigated for their combined anti-inflammatory and antioxidant potential. The chemical robustness of the connection between drug and H2S-delivery components, however, is a key and controllable linkage in these compounds. Because esters are susceptible to hydrolysis, particularly under acidic conditions such as stomach acid in oral drug delivery applications, we report here a simple synthesis of amino-ADT (ADT-NH2) and provide conditions for successful ADT-NH2 derivatization with the drugs naproxen and valproic acid. Using UV-vis spectroscopy and HPLC analysis, we demonstrate that amide-functionalized ADT derivatives are significantly more resistant to hydrolysis than ester-functionalized ADT derivatives.
This report describes a 3D microelectrode array integrated on a thin-film flexible cable for neural recording in small animals. The micro electrode array fabrication process integrates traditional silicon thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography. While direct laser writing of 3D printed electrodes has been described before, this report is the first to provide a method for high-aspect-ratio laser-written structures integrated with microfabricated electrical traces. One prototype is a 16-channel array composed of 350 micrometer long shanks spaced on a grid with 90 micrometer pitch. Other devices shown here include biomimetic mosquito-needles that penetrate through the dura of birds and porous electrodes designed to promote tissue ingrowth or enhance charge injection capacity for neural stimulation. These devices are just a few examples of a new design space that will enable high-channel-count 3D electrode arrays with features definable at single micrometer resolution. Using a custom laser writer, the 3D printing process is rapid (1 mm3/min). This high-speed printing combined with standard wafer-scale processes will enable efficient device fabrication and new studies examining the relationship between electrode geometry and electrode performance. We anticipate highest impact in small animal models, nerve interfaces, retinal implants, and other applications requiring small, high density 3D electrodes.
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