Decoupling Transmission and Transduction for Improved Durability of Highly Stretchable, Soft Strain Sensing: Applications in Human Health Monitoring.

This work presents a modular approach to the development of strain sensors for large deformations. The proposed method separates the extension and signal transduction mechanisms using a soft, elastomeric transmission and a high-sensitivity microelectromechanical system (MEMS) transducer. By separating the transmission and transduction, they can be optimized independently for application-specific mechanical and electrical performance. This work investigates the potential of this approach for human health monitoring as an implantable cardiac strain sensor for measuring global longitudinal strain (GLS). The durability of the sensor was evaluated by conducting cyclic loading tests over one million cycles, and the results showed negligible drift. To account for hysteresis and frequency-dependent effects, a lumped-parameter model was developed to represent the viscoelastic behavior of the sensor. Multiple model orders were considered and compared using validation and test data sets that mimic physiologically relevant dynamics. Results support the choice of a second-order model, which reduces error by 73% compared to a linear calibration. In addition, we evaluated the suitability of this sensor for the proposed application by demonstrating its ability to operate on compliant, curved surfaces. The effects of friction and boundary conditions are also empirically assessed and discussed.

Microfluidic Immiscible Phase Filtration System for the Isolation of Small Numbers of Cells from Whole Blood.

Isolation of circulating tumor cells (CTCs) has generated clinical and academic interest due to the important role that CTCs play in cancer metastasis and diagnosis. Here, we present a PDMS and glass prototype of a microfluidic device for the immunomagnetic, immiscible phase filtration based capture, and isolation of MCF-7 breast cancer cells, from various sample matrices including PBS-based buffer, blood plasma, and unprocessed whole blood. Following optimization of surface energy of an oil-water interface, microfluidic geometry, and bead-binding kinematics, our microfluidic device achieved 95 ± 4% recovery of target cells from PBS-based buffer with 95% purity, 90 ± 3% recovery of target cells from blood plasma and recovery of ~70 ± 5% from unprocessed whole blood with purity >99% with 1 ml blood samples with 1,000 spiked target cells. From quantitative studies to assess the nonspecific carryover of contaminants from whole blood, we found that our system accomplishes a >175 fold depletion in platelets, >900 fold depletion in erythrocytes, and >1,700 fold depletion in leukocytes with respect to unprocessed whole blood, enabling us to avoid sample pre-processing. In addition, we found that ~95% of the isolated target cells were viable, making them suitable for subsequent molecular and cellular studies. We quantify and propose mechanisms for the carryover of platelet, erythrocyte, and leukocyte contamination in purified samples, rather than relying on sample pre-processing. These results validate the continued study of our platform for extraction of CTCs from patient samples and other rare cell isolation applications. © 2019 International Society for Advancement of Cytometry.

Circulatory Support: Artificial Muscles for the Future of Cardiovascular Assist Devices.

Artificial muscles enable the design of soft implantable devices which are poised to transform the way we mechanically support the heart today. Heart failure is a prevalent and deadly disease, which is treated with the implantation of rotary blood pumps as the only alternative to heart transplantation. The clinically used mechanical devices are associated with severe adverse events, which are reflected here in a comprehensive list of critical requirements for soft active devices of the future: low power, no blood contact, pulsatile support, physiological responsiveness, high cycle life, and less-invasive implantation. In this review, prior art in artificial muscles for their applicability in the short and long term is investigated and critically evaluated. The main challenges regarding the effectiveness, controllability, and implantability of recently proposed actuators are highlighted and the future perspectives for attachment, physiological responsiveness, durability, and biodegradability as well as equitable design considerations are explored.

DynaRing: A Patient-Specific Mitral Annuloplasty Ring With Selective Stiffness Segments.

Annuloplasty ring choice and design are critical to the long-term efficacy of mitral valve (MV) repair. DynaRing is a selectively compliant annuloplasty ring composed of varying stiffness elastomer segments, a shape-set nitinol core, and a cross diameter filament. The ring provides sufficient stiffness to stabilize a diseased annulus while allowing physiological annular dynamics. Moreover, adjusting elastomer properties provides a mechanism for effectively tuning key MV metrics to specific patients. We evaluate the ring embedded in porcine valves with an ex-vivo left heart simulator and perform a 150 million cycle fatigue test via a custom oscillatory system. We present a patient-specific design approach for determining ring parameters using a finite element model optimization and patient MRI data. Ex-vivo experiment results demonstrate that motion of DynaRing closely matches literature values for healthy annuli. Findings from the patient-specific optimization establish DynaRing's ability to adjust the anterior-posterior and intercommissural diameters and saddle height by up to 8.8%, 5.6%, 19.8%, respectively, and match a wide range of patient data.

A new open-access platform for measuring and sharing mTBI data.

Despite numerous research efforts, the precise mechanisms of concussion have yet to be fully uncovered. Clinical studies on high-risk populations, such as contact sports athletes, have become more common and give insight on the link between impact severity and brain injury risk through the use of wearable sensors and neurological testing. However, as the number of institutions operating these studies grows, there is a growing need for a platform to share these data to facilitate our understanding of concussion mechanisms and aid in the development of suitable diagnostic tools. To that end, this paper puts forth two contributions: (1) a centralized, open-access platform for storing and sharing head impact data, in collaboration with the Federal Interagency Traumatic Brain Injury Research informatics system (FITBIR), and (2) a deep learning impact detection algorithm (MiGNet) to differentiate between true head impacts and false positives for the previously biomechanically validated instrumented mouthguard sensor (MiG2.0), all of which easily interfaces with FITBIR. We report 96% accuracy using MiGNet, based on a neural network model, improving on previous work based on Support Vector Machines achieving 91% accuracy, on an out of sample dataset of high school and collegiate football head impacts. The integrated MiG2.0 and FITBIR system serve as a collaborative research tool to be disseminated across multiple institutions towards creating a standardized dataset for furthering the knowledge of concussion biomechanics.

Centrifugal Microfluidics Traps for Parallel Isolation and Imaging of Single Cells.

Analysis at the single cell level has becoming an increasingly important procedure to diagnose cancer tissue biopsies. These tissue samples are often heterogeneous and consist of 1000-15,000 cells. We study the use of centrifugal microfluidics to isolate single cells into micro chambers. We describe the optimization of our microfluidics flow device, characterize its performance using both polystyrene beads as a cell analogue and MCF-7 breast cancer cells, and discuss potential applications for the device. Our results show rapid isolation of ~2000 single cell aliquots in ~20 min. We were able to occupy 65% of available chambers with singly occupied cancer cells, and observed capture efficiencies as high as 80% using input samples ranging from 2000 to 15,000 cells in 20 min. We believe our device is a valuable research tool that addresses the unmet need for massively parallel single cell level analysis of cell populations.

Enabling In-Bore MRI-Guided Biopsies With Force Feedback.

Limited physical access to target organs of patients inside an MRI scanner is a major obstruction to real-time MRI-guided interventions. Traditional teleoperation technologies are incompatible with the MRI environment and although several solutions have been explored, a versatile system that provides high-fidelity haptic feedback and access deep inside the bore remains a challenge. We present a passive and nearly frictionless MRI-compatible hydraulic teleoperator designed for in-bore liver biopsies. We describe the design components, characterize the system transparency, and evaluate the performance with a user study in a laboratory and a clinical setting. The results demonstrate % difference between input and output forces during realistic manipulation. A user study with participants conducting mock needle biopsy tasks indicates that a remote operator performs equally well when using the device as when holding a biopsy needle directly in hand. Additionally, MRI compatibility tests show no reduction in signal-to-noise ratio in the presence of the device.