Search bioRxiv⌕ Search

Biology subjects

Ulusan, H.

Publications and source records attributed to Ulusan, H..

3 recordsLinked to original sources

CardioMEA: Comprehensive Data Analysis Platform for Studying Cardiac Diseases and Drug Responses

In recent years, high-density microelectrode arrays (HD-MEAs) have emerged as a valuable tool in preclinical research for characterizing the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). HD-MEAs enable the capturing of both extracellular and intracellular signals on a large scale, while minimizing potential damage to the cell. However, a gap exists between technological advancements of HD-MEAs and the availability of effective data-analysis platforms. To address this need, we introduce CardioMEA, a comprehensive data-analysis platform designed specifically for HD-MEA data that have been obtained from iPSC-CMs. CardioMEA features scalable data processing pipelines and an interactive web-based dashboard for advanced visualization and analysis. In addition to its core functionalities, CardioMEA incorporates modules designed to discern crucial electrophysiological features between diseased and healthy iPSC-CMs. Notably, CardioMEA has the unique capability to analyze both extracellular and intracellular signals, thereby facilitating customized analyses for specific research tasks. We demonstrate the practical application of CardioMEA by analyzing electrophysiological signals from iPSC-CM cultures exposed to seven antiarrhythmic drugs. CardioMEA holds great potential as an intuitive, user-friendly platform for studying cardiac diseases and assessing drug effects.

bioengineering↗

Direct-print three-dimensional electrodes for large-scale, high-density, and customizable neural interfaces

Silicon-based planar microelectronics is a powerful tool for scalably recording and modulating neural activity at high spatiotemporal resolution, but it remains challenging to target neural structures in three dimensions (3D). We present a method for directly fabricating 3D arrays of tissue-penetrating microelectrodes onto silicon microelectronics. Leveraging a high-resolution 3D printing technology based on 2-photon polymerization and scalable microfabrication processes, we fabricated arrays of 6,600 microelectrodes 10-130 {micro}m tall and at 35-m pitch onto a planar silicon-based microelectrode array. The process enables customizable electrode shape, height and positioning for precise targeting of neuron populations distributed in 3D. As a proof of concept, we addressed the challenge of specifically targeting retinal ganglion cell (RGC) somas when interfacing with the retina. The array was customized for insertion into the retina and recording from somas while avoiding the axon layer. We verified locations of the microelectrodes with confocal microscopy and recorded high-resolution spontaneous RGC activity at cellular resolution. This revealed strong somatic and dendritic components with little axon contribution, unlike recordings with planar microelectrode arrays. The technology could be a versatile solution for interfacing silicon microelectronics with neural structures and modulating neural activity at large scale with single-cell resolution.

neuroscience↗

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. Using thin film electrocorticography (ECoG) arrays, this cortical activity has been used to decode speech and individual finger movements, enabling neuroprosthetics, and to localize epileptic foci. However, the connectorization of these multi-thousand channel thin-film arrays to external circuitry is challenging; current state-of-the-art methods are complex, bulky, and unscalable. We address this shortcoming by developing an electrode connector based on an ultra-conformable thin film electrode array that self-assembles onto hard silicon chip sensors, such as microelectrode arrays (MEAs) or camera sensors enabling large channel counts at high density. The interconnects are formed using microfabricated electrode pads suspended by thin support arms, termed flex2chip. Capillary-assisted assembly drives the pads to deform towards the chip surface, and van der Waals forces maintain this deformation, establishing mechanical and Ohmic contact onto individual pixels. We demonstrate a 2200-channel array with a channel density of 272 channels / mm2 connected to the MEA through the flex2chip interconnection method. Thin film electrode arrays connected through the flex2chip successfully measured extracellular action potentials ex vivo. Furthermore, in a transgenic mouse model for absence epilepsy, Scn8a+/-, we observed highly variable propagation trajectories at micrometer scales, even across the duration of a single spike- and-wave discharge (SWD).

bioengineering↗