Pharmaco-Kinesis Corporation has developed an implantable pump for localized cancer-fighting drug delivery. This first-generation Nano-Impedance Biosensor (NIB) detects vascular endothelial growth factor (VEGF-165) which is a biomarker correlating to the presence of a cancerous tumor in the body. The NIB is about the size of an aspirin and can detect VEGF at levels as low as 1 to 10 protein molecules in the billions of molecules present in 1 mL of body fluid. Products using NIB technology could ultimately become available over-the-counter to enable patients to measure biomarkers for cancer and other chronic illnesses. One can envision implantable sensors to track brain natriuretic peptide or troponin to enable instant therapy delivery for cardiovascular patients.

A recent article in the Journal of the American College of Cardiology examined the use of intracardiac echocardiography (ICE) to detect cardiovascular implantable electronic device-related endocarditis.  The goal of this study from Narducci et al was to compare transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE) for the diagnosis of cardiac device–related endocarditis (CDI).  The diagnosis of infective endocarditis (IE) was established by using the modified Duke criteria based mainly on echocardiography and blood culture results.

The group prospectively enrolled 162 patients (age 72 ± 11 years; 125 male) who underwent transvenous lead extraction: 152 with CDI and 10 with lead malfunction (control group). They divided the patients with infection into 3 groups: 44 with a “definite” diagnosis of IE (group 1), 52 with a “possible” diagnosis of IE (group 2), and 56 with a “rejected” diagnosis of IE (group 3). TEE and ICE were performed before the procedure. In group 1, ICE identified intracardiac masses (ICM) in all 44 patients; TEE identified ICM in 32 patients (73%). In group 2, 6 patients (11%) had ICE and TEE both positive for ICM, 8 patients (15%) had a negative TEE but a positive ICE, and 38 patients (73%) had ICE and TEE both negative. In group 3, 2 patients (3%) had ICM both at ICE and TEE, 1 patient (2%) had an ICM at ICE and a negative TEE, and 53 patients (95%) had no ICM at ICE and TEE. ICE and TEE were both negative in the control group.

They found that ICE represents a useful technique for the diagnosis of ICM by providing improved imaging of right-sided leads and increasing the diagnostic yield compared with TEE.

Tiny Implant Chip
Image taken from http://www.wired.co.uk/news/archive/2013-03/20/implantable-chip-doctor.

A multidisciplinary Swiss team has developed a tiny implantable chip that can test blood and wirelessly transmit the information to doctors.

Giovanni de Micheli and Sandro Carrara of École Polytechnique Fédérale de Lausanne (EPFL) invented the 14mm-long device. The device is a chip fitted with five sensors and a radio transmitter and is powered via inductive coupling with a battery patch worn outside the body delivering a tenth of a watt in energy. The chip is Bluetooth-equipped to transfer the data picked up by the chip’s radio signals.

The researchers’ goals are to use the chip to monitor five different molecules which may represent five different disease states. This proof-of-concept device has exciting implications for the field of personalized medicine; each person’s biological signals can be recorded and therapy tailored for each individual.

Afib on Iphone Image taken from Heart Rhythm 2013;10:315-319.

A recent article in the Heart Rhythm Journal examines the performance of a smart-phone based application to detect atrial fibrillation. McManus et al conducted real-time analyses using two different statistical methods: root mean square of successive RR differences and Shannon entropy. They found that an algorithm combining both methods demonstrated excellent sensitivity (0.962), specificity (0.975), and accuracy (0.968) for beat-to-beat discrimination of an irregular pulse during afib from sinus rhythm. In an editorial, Dr. Dave Callans (from the University of Pennsylvania) congratulated the authors for this promising new strategy but raised questions on the clinical utility of this application in the absence of better strategies to manage and interpret this new data.

Tiny Resorbable Semiconductors: Smooth as Silk ‘Transient Electronics’ Dissolve in Body or Environment

Researchers from the University of Illinois at Urbana-Champaign recently developed silk-silicon implantable microcircuits that begin to dissolve two weeks after implantation.  These particular implantable devices were designed to produce heat to fight infection after surgery.  When the device were implanted in mice, they found that infection was reduced and only faint traces of the device remained after three weeks.  These transient implantable devices may have far-ranging applications not only in medicine but in reducing electronic waste.

Current pacemaker therapy requires the use of an electronic pacemaker and implantable leads (What is a Pacemaker? ).  There have been reports of leadless pacemakers that use an implantable yet leadless means to pace the heart (Nanostim Leadless Pacemaker).  A group has recently reported results of their study examining the implantation of pacemaker-related genes.  (Biological Pacemaker using Genes)  A biological pacemaker has the advantages of no indwelling hardware and may eliminate risk of infection from traditional pacemakers.

Cingolani et al utilized a right femoral vein transvenous approach to deliver pacemaker-related genes to the atrioventricular (AV) junction.  Genes expressing dominant-negative inward rectifier potassium channel (Kir2.1AAA) and hyperpolarization-activated cation channel (HCN2) genes were used;  these are responsible for the pacemaker current (If, HCN2) and suppression of the inward rectifier current (Kir2.1).  This overexpression results in junctional pacemaker activity for up to 2weeks.  They found a septal activation pattern similar to those seen during sinus rhythm;  thus, this biological pacemaker may not cause dyssynchrony seen in right ventricular (RV) apical pacing.

Aside from gene overexpression, pluripotent stem cells and specific factors (T box transcription factors) may offer biological pacemaker activity as well.  Obviously, these are all preclinical techniques that may offer an exciting alternative to current electronic, implantable pacemakers.

Nokia has introduced a smart phone that can charge itself wirelessly. (http://www.nokia.com/global/products/lumia/)  It is safe to assume that Nokia uses induction based technology to charge the phone. The phone (equipped with a special receiver) is placed on a mat that generates an electromagnetic field. The phone’s special receiver uses this electromagnetic field to charge the phone’s battery. This technology can only power one device at a time and may generate heat during the charging process.

Recently, IDT and Intel partnered to announce the development of an integrated transmitter and receiver chipset for Intel’s wireless charging technology based on resonance technology. (IDT and Intel Partnership)  Magnetic resonance uses electrical components (a coil and a capacitor) to create magnetic resonance. This resonance can then transmit electricity to the receiver (device to be charged) from the transmitter (charging base). Magnetic resonance can power multiple devices at a time and may not generate excessive heat. A nice summary of this technology is available at Fujitsu Summary of Wireless Charging.

These technologies can be disruptive forces in the medical device industry that rely on battery depletion and replacement for subsequent sales (e.g., pacemakers, defibrillator, and noncardiac pulse generators). The device company that incorporates wireless charging into their devices may minimize replacement procedures for patients (and limiting procedural risk) while at the same time stabilizing their market position. Future device upgrades may be software upgrades and licensing that can be performed wirelessly without need for invasive procedure.

Researchers at the Fraunhofer Institute for Microelectronic Circuits and Systems IMS in Duisburg have developed an implantable biosensor that can measure glucose in sweat or tears obviating the need for needlesticks.  An electrochemical reaction using glucose oxidase that converts glucose into hydrogen peroxide; this concentration can be measured with a potentiostat and these measurements are used to calculate the glucose level. This biosensor has incorporated the entire diagnostic circuit into a fully implantable tiny sensor.  The biosensor can transmit the data via a wireless interface to a mobile receiver or even smart phone.

Biosensor Measures Glucose in Sweat and Tears

The effects of intracardiac ablation have been well characterized (See Effects of RFA) and prior work has suggested that it can be used to repair mitral valve prolapse causing severe mitral regurgitation (MR).  Minimally invasive repair of mitral valve prolapse (MVP) causing severe mitral regurgitation (MR) should increase the rigidity of the valve leaflet, decrease the leaflet surface area, and decrease redundant chordal length. Ex-vivo studies suggest that direct application of radiofrequency ablation (RFA) to mitral leaflets and chordae can effect these repair goals to decrease MR.  We used a naturally occurring model of MVP (similar macroscopically and microscopically to primary MVP in humans) causing severe MR.  RFA was applied to the prolapsed leaflets of the mitral valve and any associated elongated chordae. Mitral regurgitant volume was calculated using the proximal isovelocity surface area method on pre- and post-ablation echocardiograms.  Subjects found to have anterior leaflet, posterior leaflet, and bileaflet MVP prolapse causing severe MR with a mean ejection fraction of 66±3%(±SD) underwent direct RFA. Echocardiograms performed before and after RFA demonstrated a 66.9±20.6% reduction in mitral regurgitant volume.  The first video below shows the severe MR prior to RFA application to leaflets and chordae.  The second video shows the degree of MR 6weeks after RFA applied.  One can note the qualitative decrease in MR that was quantified by doppler.

These data suggest that myxomatous mitral valve repair using radiofrequency energy delivered via catheter may be feasible. Further investigation is necessary to evaluate whether such a technique could be adapted to a percutaneous, closed chest, beating heart environment.

More information about this study can be found at:  http://www.lebanoncardiology.com/downloads/JLW%20JOIC%202008.pdf.

These researchers describe an amperometric sensor for the detection of ethanol in the extracellular fluid of animal brains.

http://pubs.acs.org/doi/abs/10.1021/ac301253h

Ethanol is one of the most widespread psychotropic agents in western society. While its psychoactive effects are mainly associated to GABAergic and glutamatergic systems, the positive reinforcing properties of ethanol are related to activation of mesolimbic dopaminergic pathways resulting in a release of dopamine in the nucleus accumbens. Given these neurobiological implications, the detection of ethanol in brain extracellular fluid (ECF) is of great importance. In this study we describe the development and characterization of an implantable biosensor for the amperometric detection of brain ethanol in real time. Ten different designs were characterized in vitro in terms of Michaelis–Menten kinetics (VMAX and KM), sensitivity (linear region slope, LOD and LOQ), and electroactive interference blocking. The same parameters were monitored in selected designs up to 28 days after fabrication in order to quantify their stability. Finally, the best performing biosensor design was selected for implantation in the nucleus accumbens and coupled with a previously-developed telemetric device for the real-time monitoring of ethanol in freely moving, untethered rats. Ethanol was then administered systemically to animals, either alone or in combination with ranitidine (an alcohol dehydrogenase inhibitor) while the biosensor signal was continuously recorded. The implanted biosensor, integrated in a low-cost telemetry system, was demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in brain ECF, and represents a new generation of analytical tools for studying ethanol toxicokinetics and the effect of drugs on brain ethanol levels.