Detection of Blood Clots Using a Whole Stent as an Active Implantable Biosensor.

Many cardiovascular problems stem from blockages that form within the vasculature and often treatment includes fitting a stent through percutaneous coronary intervention. This offers a minimally invasive therapy but re-occlusion through restenosis or thrombosis formation often occurs post-deployment. Research is ongoing into the creation of smart stents that can detect the occurrence of further problems. In this study, it is shown that selectively metalizing a non-conductive stent can create a set of electrodes that are capable of detecting a build-up of material around the stent. The associated increase in electrical impedance across the electrodes is measured, testing the stent with blood clot to mimic thrombosis. It is shown that the device is capable of sensing different amounts of occlusion. The stent can reproducibly sense the presence of clot showing a 16% +/-3% increase in impedance which is sufficient to reliably detect the clot when surrounded by explanted aorta (one sample t-test, p = 0.009, n = 9). It is demonstrated that this approach can be extended beyond the 3D printed prototypes by showing that it can be applied to a commercially available stent and it is believed that it can be further utilized by other types of medical implants.

An Impedance Sensor for Pathologically Relevant Detection of In-Stent Restenosis In Vitro.

Cardiovascular disease (CVD) is the biggest cause of death globally. CVD is caused by atherosclerosis which is the accumulation of fatty deposits, often within the fine arteries of the heart or brain. These blockages reduce blood flow and lead to oxygen starvation (ischemia) which can lead to heart attacks and strokes. To treat blocked arteries an implantable device called a stent re-opens the artery to reinstate blood flow to the organ. The stent itself can become blocked over time by cell growth (intimal hyperplasia) which is characterised by excessive smooth muscle cell proliferation. Sensors based on electrical impedance spectroscopy (EIS) embedded in a stent could detect this re-blocking to allow for early intervention. Using platinum interdigitated electrodes on silicon sensor wafers we were able to co-culture different ratios of mouse smooth muscle cells and mouse endothelial cells on these sensors. This mimics the complex, multicellular environment which a stent is found in vivo when undergoing neo-intimal hyperplasia. Trends in the cell impedances were then characterised using the detection frequency and the gradient of change between populations over time which we termed 'Peak Cumulative Gradients (PCG). PCGs were calculated to successfully discriminate each cell type. This work moves towards a sensor that may help guide clinician's decision-making in a disease that is historically silent and difficult to detect. Clinical Relevance-This moves towards an early warning system for the detection of neo intimal hyperplasia ultimately leading to a reduction in stent complications.

Challenges to the Development of the Next Generation of Self-Reporting Cardiovascular Implantable Medical Devices.

Cardiovascular disease (CVD) is a group of heart and vasculature conditions which are the leading form of mortality worldwide. Blood vessels can become narrowed, restricting blood flow, and drive the majority of hearts attacks and strokes. Reactive surgical interventions are frequently required; including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Despite successful opening of vessels and restoration of blood flow, often in-stent restenosis (ISR) and graft failure can still occur, resulting in subsequent patient morbidity and mortality. A new generation of cardiovascular implants that have sensors and real-time monitoring capabilities are being developed to combat ISR and graft failure. Self-reporting stent/graft technology could enable precision medicine-based and predictive healthcare by detecting the earliest features of disease, even before symptoms occur. Bringing an implantable medical device with wireless electronic sensing capabilities to market is complex and often obstructive undertaking. This critical review analyses the obstacles that need to be overcome for self-reporting stents/grafts to be developed and provide a precision-medicine based healthcare for cardiovascular patients. Here we assess the latest research and technological advancement in the field, the current devices; including smart cardiovascular implantable biosensors and associated wireless data and power transfer solutions. We include an evaluation of devices that have reached clinical trials and the market potential for their end-user implementation.

Impedimetric Detection and Electromediated Apoptosis of Vascular Smooth Muscle Using Microfabricated Biosensors for Diagnosis and Therapeutic Intervention in Cardiovascular Diseases.

Cardiovascular diseases remain a significant global burden with 1-in-3 of all deaths attributable to the consequences of the disease. The main cause is blocked arteries which often remain undetected. Implantable medical devices (IMDs) such as stents and grafts are often used to reopen vessels but over time these too will re-block. A vascular biosensor is developed that can report on cellularity and is amenable to being mounted on a stent or graft for remote reporting. Moreover, the device is designed to also receive currents that can induce a controlled form of cell death, apoptosis. A combined diagnostic and therapeutic biosensor would be transformational for the treatment of vascular diseases such as atherosclerosis and central line access. In this work, a cell sensing and cell apoptosing system based on the same interdigitated electrodes (IDEs) is developed. It is shown that the device is scalable and that by miniaturizing the IDEs, the detection sensitivity is increased. Apoptosis of vascular smooth muscle cells is monitored using continuous impedance measurements at a frequency of 10 kHz and rates of cell death are tracked using fluorescent dyes and live cell imaging.