Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant.

Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.

Pyrolytic Carbon Nanograss Enhances Neurogenesis and Dopaminergic Differentiation of Human Midbrain Neural Stem Cells.

Advancements in research on the interaction of human neural stem cells (hNSCs) with nanotopographies and biomaterials are enhancing the ability to influence cell migration, proliferation, gene expression, and tailored differentiation toward desired phenotypes. Here, the fabrication of pyrolytic carbon nanograss (CNG) nanotopographies is reported and demonstrated that these can be employed as cell substrates boosting hNSCs differentiation into dopaminergic neurons (DAn), a long-time pursued goal in regenerative medicine based on cell replacement. In the near future, such structures can play a crucial role in the near future for stem-cell based cell replacement therapy (CRT) and bio-implants for Parkinson's disease (PD). The unique combination of randomly distributed nanograss topographies and biocompatible pyrolytic carbon material is optimized to provide suitable mechano-material cues for hNSCs adhesion, division, and DAn differentiation of midbrain hNSCs. The results show that in the presence of the biocoating poly-L-lysine (PLL), the CNG enhances hNSCs neurogenesis up to 2.3-fold and DAn differentiation up to 3.5-fold. Moreover, for the first time, consistent evidence is provided, that CNGs without any PLL coating are not only supporting cell survival but also lead to significantly enhanced neurogenesis and promote hNSCs to acquire dopaminergic phenotype compared to PLL coated topographies.

Dopamine Detection using Mercaptopropionic Acid and Cysteamine for Electrodes Surface Modification.

Gold electrodes are often not suitable for dopamine measurements as dopamine creates a non-conducting polymer layer on the surface of the electrodes, which leads to increased amount of electrode passivity with the gradual increase in voltammograms measurement. This work presents the impedance spectroscopy and cyclic-voltammetry comparative study for dopamine detection with two modifications for the surface of Au electrodes; cysteamine and mercaptopropionic acid for thermally bonded and ultrasonically welded microfluidic chips, respectively. The effects of optimized tubing selection, bonding techniques, and cleaning methods of the devices with KOH solution played crucial role for improvements in dopamine detection, which are observed in the results. Furthermore, comparison for the modification with unmodified chips, and finding the unknown concentration of dopamine solution using flow injection techniques, is also illustrated.

Design and Simulation of Microfluidic Device for Metabolite Screening and Quantitative Monitoring of Drug Uptake in Cancer Cells.

Although liquid-liquid extraction methods are currently being applied in many areas such as analytical chemistry, biochemical engineering, biochemistry, and biological applications, accessibility and usability of microfluidics in practical daily life fields are still bounded. Suspended microfluidic devices have the potential to lessen the obstacles, but the absence of robust design rules have hampered their usage. The primary objective of this work is to design and fabricate a microfluidic device to quantitatively monitor the drug uptake of cancer cells. Liquid-liquid extraction is used to quantify the drug uptake. In this research work, designs and simulations of two different microfluidic devices for carrying out multiplex solution experiments are proposed to test their efficiency. These simplified miniaturized chips would serve as suspended microfluidic metabolites extraction platform as it allows extracting the metabolites produced from the cancer cells as a result of applying a specific drug type for a certain period of time. These devices would be fabricated by making polydimethylsiloxane (PDMS) molds from the negative master mold using soft lithography. Furthermore, it can leverage to provide versatile functionalities like high throughput screening, cancer cell invasions, protein purification, and small molecules extractions. As per previous studies, PDMS has been depicting better stability with various solvents and has proved to be a reliable and cost effective material to be used for fabrication, though the sensitivity of the chip would be analyzed by cross contamination and of solvents within the channels of device.

Retraction.

[This retracts the article DOI: 10.2478/joeb-2018-0002.].