Dynamic detection and reversal of myocardial ischemia using an artificially intelligent bioelectronic medicine.

Myocardial ischemia is spontaneous, frequently asymptomatic, and contributes to fatal cardiovascular consequences. Importantly, myocardial sensory networks cannot reliably detect and correct myocardial ischemia on their own. Here, we demonstrate an artificially intelligent and responsive bioelectronic medicine, where an artificial neural network (ANN) supplements myocardial sensory networks, enabling reliable detection and correction of myocardial ischemia. ANNs were first trained to decode spontaneous cardiovascular stress and myocardial ischemia with an overall accuracy of ~92%. ANN-controlled vagus nerve stimulation (VNS) significantly mitigated major physiological features of myocardial ischemia, including ST depression and arrhythmias. In contrast, open-loop VNS or ANN-controlled VNS following a caudal vagotomy essentially failed to reverse cardiovascular pathophysiology. Last, variants of ANNs were used to meet clinically relevant needs, including interpretable visualizations and unsupervised detection of emerging cardiovascular stress. Overall, these preclinical results suggest that ANNs can potentially supplement deficient myocardial sensory networks via an artificially intelligent bioelectronic medicine system.

Liquid biopsy using the nanotube-CTC-chip: capture of invasive CTCs with high purity using preferential adherence in breast cancer patients.

In this paper, we report the development of the nanotube-CTC-chip for isolation of tumor-derived epithelial cells (circulating tumor cells, CTCs) from peripheral blood, with high purity, by exploiting the physical mechanisms of preferential adherence of CTCs on a nanotube surface. The nanotube-CTC-chip is a new 76-element microarray technology that combines carbon nanotube surfaces with microarray batch manufacturing techniques for the capture and isolation of tumor-derived epithelial cells. Using a combination of red blood cell (RBC) lysis and preferential adherence, we demonstrate the capture and enrichment of CTCs with a 5-log reduction of contaminating WBCs. EpCAM negative MDA-MB-231/luciferase-2A-green fluorescent protein (GFP) cells were spiked in the blood of wild mice and enriched using an RBC lysis protocol. The enriched samples were then processed using the nanotube-CTC-chip for preferential CTC adherence on the nanosurface and counting the GFP cells yielded anywhere from 89% to 100% capture from the droplets. Electron microscopy (EM) studies showed focal adhesion with filaments from the cell body to the nanotube surface. We compared the nanotube preferential adherence to collagen adhesion matrix (CAM) scaffolding, reported as a viable strategy for CTC capture in patients. The CAM scaffolding on the device surface yielded 50% adherence with 100% tracking of cancer cells (adhered vs. non-adhered) versus carbon nanotubes with >90% adherence and 100% tracking for the same protocol. The nanotube-CTC-chip successfully captured CTCs in the peripheral blood of breast cancer patients (stage 1-4) with a range of 4-238 CTCs per 8.5 ml blood or 0.5-28 CTCs per ml. CTCs (based on CK8/18, Her2, EGFR) were successfully identified in 7/7 breast cancer patients, and no CTCs were captured in healthy controls (n = 2). CTC enumeration based on multiple markers using the nanotube-CTC-chip enables dynamic views of metastatic progression and could potentially have predictive capabilities for diagnosis and treatment response.

Publisher Correction: Exfoliated WS2-Nafion Composite based Electromechanical Actuators.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Publisher Correction: Exfoliated WS2-Nafion Composite based Electromechanical Actuators.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Exfoliated WS2-Nafion Composite based Electromechanical Actuators.

The ability to convert electrical energy into mechanical motion is of significant interest in many energy conversion technologies. Here, we demonstrate the first liquid phase exfoliated WS2-Nafion nanocomposite based electro-mechanical actuators. Highly exfoliated layers of WS2 mixed with Nafion solution, solution cast and doped with Li+ was studied as electromechanical actuators. Resonant Raman spectroscopy, X-ray photo-electron-spectroscopy, differential scanning calorimetry, dynamic mechanical analysis, and AC impedance spectroscopy were used to study the structure, photoluminescence, water uptake, mechanical and electromechanical actuation properties of the exfoliated nanocomposites. A 114% increase in elastic modulus (dry condition), 160% increase in proton conductivity, 300% increase in water uptake, cyclic strain amplitudes of ~0.15% for 0.1 Hz excitation frequency, tip displacements greater than nanotube-Nafion and graphene-Nafion actuators and continuous operation for more than 5 hours is observed for TMD-Nafion actuators. The mechanism behind the increase in water uptake is a result of oxygen atoms occupying the vacancies in the hydrophilic exfoliated flakes and subsequently bonding with water, not possible in Nafion composites based on carbon nanotube and graphene.