PMC:2992534 / 1808-5039 JSONTXT

{"project":"2_test","denotations":[{"id":"21050471-12900339-6241102","span":{"begin":307,"end":308},"obj":"12900339"},{"id":"21050471-15276392-6241103","span":{"begin":875,"end":876},"obj":"15276392"},{"id":"21050471-17438147-6241104","span":{"begin":1069,"end":1070},"obj":"17438147"},{"id":"21050471-15116951-6241105","span":{"begin":1967,"end":1968},"obj":"15116951"},{"id":"21050471-15844324-6241105","span":{"begin":1967,"end":1968},"obj":"15844324"},{"id":"21050471-16076436-6241105","span":{"begin":1967,"end":1968},"obj":"16076436"}],"text":"Background\nCoronary stents, which are routinely used to treat blocked arteries, are recognized by the body as foreign objects and can incite an immune response and cause re-occlusion of the artery. Thus, stents that elute immunosuppressive drugs have been developed that decrease this risk of re-occlusion [1,2]. These drug-eluting stents can also prevent the healing process where the stent is encapsulated in endothelial cells. The lumen is then constantly exposed to bare surfaces where clots can form at any time, even years after implantation [3]. Presently, clots are prevented pharmaceutically with clopidogrel for 12 months and aspirin indefinitely [4]. These guidelines are based on clinical averages and are not individualized based on the healing of a specific patient's stent. These drugs put the patient at risk of hemorrhaging, especially when co-administered [5].\nPost-mortem analysis indicates that the most powerful histological predictor for late stent thrombosis is endothelial coverage, specifically, the ratio of covered to uncovered stent struts [6]. A stent that actively monitors endothelial coverage would allow physicians to better individualize a patient's anti-platelet therapy based on their clotting risk. Embedding these sensors along several struts in a stent would give detailed information regarding the level of healing in an individual patient. This article presents the development of such a sensor that consists of a commercially available piezoelectric cantilever (DMASP, Veeco Probes), which has a film of zinc oxide used to actuate the cantilever in AFM imaging applications (Figure 1). Micromachined cantilevers lend themselves well to numerous sensing applications. Attachment of molecules or whole cells onto the cantilever surface alters the effective mass and surface stress of the cantilever, and causes a shift in the cantilever's resonance frequency, as has been demonstrated previously as sensors for cell detection [7-11]. Cantilevers with integrated piezoelectric sensing elements do not require alignment of an external laser and are not affected by changes in surface reflectivity or the index of refraction of the operating fluid, allowing a more compact system. We have insulated the cantilever, allowing us to readily detect resonant frequencies in a fluid environment.\nFigure 1 Veeco active probe. Cantilever consists of a Si substrate (thickness = 4 μm) supporting a ZnO stack (0.25 μm Ti/Au, 3.5 μm ZnO, and 0.25 μm Ti/Au). Other relevant dimensions are shown in microns. The sensor will interface with an active stent device our lab has been developing as shown in Figure 2. By coupling a stent with a sub-mm3 fully wireless implantable cardiac monitoring integrated circuit, we have created an active cardiac sensing platform which can measure pressure, flow, and oxygenation [12-14]. The stent itself is used as an antenna for wireless telemetry and powering. The sensor we have developed here will couple to this active stent to provide real-time diagnostic information regarding stent endothelial coverage without additional invasive procedures.\nFigure 2 Active stent. Active electronics sealed in a liquid crystal polymer package and integrated with a stent.\n\nM"}