fabrication-ti3c2-mxene-microelectrode-arrays-for-vivo-neural

Fabrication of Ti3C2 MXene Microelectrode Arrays for In Vivo Neural Recording

Implantable microelectrode technologies have been widely used to elucidate neural dynamics at the microscale to gain a deeper understanding of the neural ...

University of Pennsylvania

Corporal Michael J. Crescenz Veterans Affairs Medical Center

Traditional approaches to evaluating antitumor agents using human tumor xenograft models have generally used cohorts of 8 to 10 mice against a limited panel of tumor models. An alternative approach is to use fewer animals per tumor line, allowing a greater number of models that capture greater molecular/genetic heterogeneity of the cancer type. We retrospectively analyzed 67 agents evaluated by the Pediatric Preclinical Testing Program to determine whether a single mouse, chosen randomly from each group of a study, predicted the median response for groups of mice using 83 xenograft models. The individual tumor response from a randomly chosen mouse was compared with the group median response using established response criteria. A total of 2,134 comparisons were made. The single tumor response accurately predicted the group median response in 1,604 comparisons (75.16%). The mean tumor response correct prediction rate for 1,000 single mouse random samples was 78.09%. Models had a range for correct prediction (60%-87.5%). Allowing for misprediction of ± one response category, the overall mean correct single mouse prediction rate was 95.28%, and predicted overall objective response rates for group data in 66 of 67 drug studies. For molecularly targeted agents, occasional exceptional responder models were identified and the activity of that agent confirmed in additional models with the same genotype. Assuming that large treatment effects are targeted, this alternate experimental design has similar predictive value as traditional approaches, allowing for far greater numbers of models to be used that more fully encompass the heterogeneity of disease types. Cancer Res; 76(19); 5798-809. ©2016 AACR.

Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis.

Intracranial electrodes are a vital component of implantable neurodevices, both for acute diagnostics and chronic treatment with open and closed-loop neuromodulation. Their performance is hampered by acute implantation trauma and chronic inflammation in response to implanted materials and mechanical mismatch between stiff synthetic electrodes and pulsating, natural soft host neural tissue. Flexible electronics based on thin polymer films patterned with microscale conductive features can help alleviate the mechanically induced trauma; however, this strategy alone does not mitigate inflammation at the device-tissue interface. In this study, we propose a biomimetic approach that integrates microscale extracellular matrix (ECM) coatings on microfabricated flexible subdural microelectrodes. Taking advantage of a high-throughput process employing micro-transfer molding and excimer laser micromachining, we fabricate multi-channel subdural microelectrodes primarily composed of ECM protein material and demonstrate that the electrochemical and mechanical properties match those of standard, uncoated controls. In vivo ECoG recordings in rodent brain confirm that the ECM microelectrode coatings and the protein interface do not alter signal fidelity. Astrogliotic, foreign body reaction to ECM coated devices is reduced, compared to uncoated controls, at 7 and 30 days, after subdural implantation in rat somatosensory cortex. We propose microfabricated, flexible, biomimetic electrodes as a new strategy to reduce inflammation at the device-tissue interface and improve the long-term stability of implantable subdural electrodes.

Article	Year
Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis. Cancer research\| PubMed ID: 27496711	2016
Biomimetic extracellular matrix coatings improve the chronic biocompatibility of microfabricated subdural microelectrode arrays. PloS one\| PubMed ID: 30383805	2018

Brendan Murphy

Biography

JoVE Journal Publications

Other Publications