A microwell-based impedance sensor on an insertable microneedle for real-time in vivo cytokine detection.

Impedance-based protein detection sensors for point-of-care diagnostics require quantitative specificity, as well as rapid or real-time operation. Furthermore, microfabrication of these sensors can lead to the formation of factors suitable for in vivo operation. Herein, we present microfabricated needle-shaped microwell impedance sensors for rapid-sample-to-answer, label-free detection of cytokines, and other biomarkers. The microneedle form factor allows sensors to be utilized in transcutaneous or transvascular sensing applications. In vitro, experimental characterization confirmed sensor specificity and sensitivity to multiple proteins of interest. Mechanical characterization demonstrated sufficient microneedle robustness for transcutaneous insertion, as well as preserved sensor function postinsertion. We further utilized these sensors to carry out real-time in vivo quantification of human interleukin 8 (hIL8) concentration levels in the blood of transgenic mice that endogenously express hIL8. To assess sensor functionality, hIL8 concentration levels in serum samples from the same mice were quantified by ELISA. Excellent agreement between real-time in vivo sensor readings in blood and subsequent ELISA serum assays was observed over multiple transgenic mice expressing hIL8 concentrations from 62 pg/mL to 539 ng/mL.

Biomimetic extracellular matrix coatings improve the chronic biocompatibility of microfabricated subdural microelectrode arrays.

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.

Designing Surface Chemistry of Silver Nanocrystals for Radio Frequency Circuit Applications.

We introduce solution-based, room temperature- and atmospheric pressure-processed silver nanocrystal (Ag NC)-based electrical circuits and interconnects for radio frequency (RF)/microwave frequency applications. We chemically designed the surface and interface states of Ag NC thin films to achieve high stability, dc and ac conductivity, and minimized RF loss through stepwise ligand exchange, shell coating, and surface cleaning. The chemical and structural properties of the circuits and interconnects affect the high-frequency electrical performance of Ag NC thin films, as confirmed by high-frequency electromagnetic field simulations. An all solution-based process is developed to build coplanar structures, in which Ag NC thin films are positioned at both sides of the substrates. In addition, we fabricated flexible transmission lines and broadband electrical circuits for resistors, interdigitated capacitors, spiral and omega-shaped inductors, and patch antennas with maximum inductance and capacitance values of 3 nH and 2.5 pF at frequencies up to 20 GHz. We believe that our approach will lead to a cost-effective realization of RF circuits and devices in which sensing and wireless communication capabilities are combined for internet-of-things applications.