Age differences of patients treated with wearable cardioverter defibrillator: Data from a multicentre registry.

BACKGROUND: Wearable cardioverter defibrillators (WCD) are used as a 'bridging' technology in patients, who are temporarily at high risk for sudden cardiac death (SCD). Several factors should be taken into consideration, for example patient selection, compliance and optimal drug treatment, when WCD is prescribed. We aimed to present real-world data from seven centres from Germany and Switzerland according to age differences regarding the outcome, prognosis, WCD data and compliance. MATERIALS AND METHODS: Between 04/2012 and 03/2021, 1105 patients were included in this registry. Outcome data according to age differences (old ≥45 years compared to young <45 years) were analysed. At young age, WCDs were more often prescribed due to congenital heart disease and myocarditis. On the other hand, ischaemic cardiomyopathy (ICM) was more present in older patients. Wear days of WCD were similar between both groups (p = .115). In addition, during the WCD use, documented arrhythmic life-threatening events were comparable [sustained ventricular tachycardia: 5.8% vs. 7.7%, ventricular fibrillation (VF) .5% vs. .6%] and consequently the rate of appropriate shocks was similar between both groups. Left ventricular ejection fraction improvement was documented over follow-up with a better improvement in younger patients as compared to older patients (77% vs. 63%, p = .002). In addition, at baseline, the rate of atrial fibrillation was significantly higher in the older age group (23% vs. 8%; p = .001). The rate of permanent cardiac implantable electronic device implantation (CiED) was lower in the younger group (25% vs. 36%, p = .05). The compliance rate defined as wearing WCD at least 20 h per day was significantly lower in young patients compared to old patients (68.9% vs. 80.9%, p < .001). During the follow-up, no significant difference regarding all-cause mortality or arrhythmic death was documented in both groups. A low compliance rate of wearing WCD is predicted by young patients and patients suffering from non-ischaemic cardiomyopathies. CONCLUSION: Although the compliance rate in different age groups is high, the average wear hours tended to be lower in young patients compared to older patients. The clinical events were similar in younger patients compared to older patients.

Sex differences and adherence of patients treated with wearable cardioverter-defibrillator: Insights from an international multicenter register.

AIMS: Treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore sex differences. METHODS AND RESULTS: We analyzed 708 consecutive patients, 579 (81.8%) from whom were males and 129 (18.2%) females (age, 60.5 ± 14 vs. 61.6 ± 17 years old; p = .44). While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p = .001), females received it more frequently due to nonischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p = .009). The wear time of WCD was equivalent in both groups (21.1 ± 4.3 h/days in males vs. 21.5 ± 4.4 h/days in females; p = .27; and 62.6 ± 44.3 days in males vs. 56.5 ± 39 days in females; p = .15). Mortality was comparable in both groups at 2-year-follow-up (6.8% in males vs. 9.7% in females; p = .55). Appropriate WCD shocks and the incidence of ICD implantations were similar in both groups (2.4% in males vs. 3.9% in females; p = .07) (35.1% in males vs. 31.8% in females; p = .37), respectively. In age tertile analysis, compliance was observed more in 73-91 years old group as compared with 14-51 years old group (87.8% vs. 68.3%; p < .001). CONCLUSION: Compliance for wearing WCD was excellent regardless of sex. Furthermore, mortality and the incidence of ICD implantations were comparable in both sexes. Appropriate WCD shocks were similar in both sexes.

Avoiding implantation of a cardioverter-defibrillator by bridging with wearable defibrillator vest.

BACKGROUND: Patients with a left ventricular ejection fraction (LVEF) ≤35% should be protected from sudden cardiac death with an implantable cardioverter-defibrillator (ICD). The onset of the effect of optimal medical therapy (OMT) is unclear, and a wearable cardioverter-defibrillator (WCD) can bridge this period. PATIENTS AND METHODS: Our study analyzed 104 patients (age, 68.9 ± 11.7 years; 81% [84/104] male) whose first diagnosis included an LVEF <35%. After exclusion of reversible causes for LVEF reduction and initiation/adjustment of the OMT, the WCD was employed. The LVEF and indication for ICD were re-evaluated after 62 ± 36 days. The LVEF development and implantation rate were correlated with underlying disease (ischemic [ICM] or nonischemic cardiomyopathy [NICM]), comorbidities, and age/gender. RESULTS: The wearing time of the WCD was 22.8 ± 1.9 h/day. An LVEF improvement from 28.5 ± 6.4% to 40 ± 11.7% was achieved through OMT (p < 0.0001). An improvement in LVEF of up to more than 35% was achieved in 66 of 104 patients (63%), and only 37% of patients were subsequently given an ICD. This affected 41% of patients with ICM and 30% of patients with NICM (p = 0.205). Notably, no ICD interventions were observed over 362 ± 89.5 days after implantation in the ICD-receiver group. CONCLUSION: The indication for ICD can be re-evaluated after 2 months. Patients with NICM respond better to OMT compared with ICM patients. The LVEF recovered to >35% in >60% of cases.

Silent cerebral lesions and cognitive function after pulmonary vein isolation with an irrigated gold-tip catheter: REDUCE-TE Pilot study.

INTRODUCTION: Stroke is one of the most feared complications during catheter ablation of atrial fibrillation (AF). While symptomatic thromboembolic events are rare, magnetic resonance imaging (MRI) may identify asymptomatic (ie, silent) cerebral lesions (SCLs) following pulmonary vein isolation (PVI) procedures. METHODS AND RESULTS: The REDUCE-TE Pilot was a prospective multicenter, single-arm observational study investigating the incidence of SCL in patients with symptomatic paroxysmal AF undergoing PVI with a novel gold-tip, externally irrigated ablation catheter. After ablation, cerebral diffusion-weighted MRI and a postablation follow-up were performed at 1 to 3 days after the ablation procedure. A neurocognitive test was done before and after ablation. The primary study endpoint was the occurrence of one or more new SCLs. Secondary study endpoints included neurocognitive status, procedural success rate, and periprocedural complications including symptomatic thromboembolic events. A total of 104 patients were enrolled (69% male, mean age: 61.5 ± 9.7 years, mean CHA2 DS 2 -VASc score: 1.7 ± 1.2). Postprocedural MRI examination was performed in 97 patients, and in nine of them (9.3%; 95% CI: 4.3-16.9%) a total of 11 SCLs were detected. Univariate analyses did not reveal any significant predictor for new SCLs. Nonsignificant trends were observed for low activated clotting time during ablation and for international normalized ratio value outside the range of 2 to 3 at ablation. There was no evidence of significant deterioration of neurocognitive function after PVI. In four patients, a pericardial tamponade was noted but all patients fully recovered during follow-up. CONCLUSIONS: Ablation of AF using a novel gold-tip, externally irrigated ablation catheter, resulted in SCLs in approximately one out of 10 patients without a measurable effect on neurocognitive function.

Impact of the Right Ventricular Lead Position on Clinical End Points in CRT Recipients--A Subanalysis of the Multicenter Randomized SPICE Trial.

BACKGROUND: The impact of right ventricular (RV) lead location on clinical end points in patients undergoing cardiac resynchronization therapy (CRT) is unclear. We evaluated the impact of different RV lead locations on clinical outcome in CRT patients enrolled in the Septal Positioning of ventricular implantable cardioverter-defibrillator (ICD) Electrodes (SPICE) trial, which randomized recipients of implantable cardioverter defibrillators to apical versus midseptal RV lead positioning. METHODS: Ninety-eight CRT recipients were included in the multicenter SPICE trial and followed for 12 months: Fifty-three patients were randomized to receive an apical (A) and 45 to receive a midseptal (S) lead position. We compared echocardiographical and electrocardiographical parameters and outcome. RESULTS: Echocardiographic response with respect to improvement of left ventricular ejection fraction (A: +15.8 ± 14.6%, S: +9.7 ± 12.6%, P = 0.156) and reduction of left ventricular end-diastolic diameter (A: -4.2 ± 10.7 mm, S: -7.5 ± 10.7 mm, P = 0.141) was comparable in apical and midseptal groups. Paced QRS width neither differed at prehospital discharge (A: 129 ± 21 ms, S: 135 ± 21 ms, P = 0.133) nor at 12-month follow-up (A: 131 ± 23 ms, S: 134 ± 28 ms, P = 0.620). No differences were found with respect to the risk of ventricular tachyarrhythmia or ICD therapy. Septal RV lead position, however, was associated with a significant longer time to a first heart failure event (P = 0.040) and a longer survival time (P = 0.019). CONCLUSIONS: In CRT recipients, midseptal RV lead position was not superior with respect to improvement of echocardiographic parameters or paced QRS width. It did not predispose to ventricular arrhythmias or ICD therapy. The finding that midseptal lead position was associated with a longer time to first heart failure event and a longer survival time deserves further investigation.

Neuroprotective Strategies during Cardiac Surgery with Cardiopulmonary Bypass.

Aortocoronary bypass or valve surgery usually require cardiac arrest using cardioplegic solutions. Although, in principle, in a number of cases beating heart surgery (so-called off-pump technique) is possible, aortic or valve surgery or correction of congenital heart diseases mostly require cardiopulmonary arrest. During this condition, the heart-lung machine also named cardiopulmonary bypass (CPB) has to take over the circulation. It is noteworthy that the invention of a machine bypassing the heart and lungs enabled complex cardiac operations, but possible negative effects of the CPB on other organs, especially the brain, cannot be neglected. Thus, neuroprotection during CPB is still a matter of great interest. In this review, we will describe the impact of CPB on the brain and focus on pharmacological and non-pharmacological strategies to protect the brain.

A stepwise electrocardiographic algorithm for differentiation of mid-septal vs. apical right ventricular lead positioning: the SPICE ECG substudy.

AIMS: Right ventricular (RV) septum is a non-apical site targeted during lead implantation. Electrocardiographic (ECG) recognition of mid-septal lead location is challenging. The aim of the study is to determine ECG correlates of RV mid-septal pacing. METHODS AND RESULTS: The present study is a pre-specified analysis of a prospective, multicenter study, which randomized recipients of an implantable cardioverter defibrillator to an apical vs. mid-septal RV lead positioning. Following implantation, a 12-lead ECG was recorded during intrinsic rhythm and RV pacing. In total, 227 patients, 121 in the apical group (76.9% males, 67.1 ± 11.3 years) and 106 in the mid-septal group (82.1% males, age 64.7 ± 12.7 years) were included. Apically as compared with septally paced patients had significantly longer paced QRS duration (177.0 ± 25.0 vs. 170.4 ± 21.7, respectively, P = 0.03) and significantly more leftward paced QRS axis (-71.6 ± 33.3° vs. 9.4 ± 86.5°, respectively, P < 0.001). A significantly higher proportion of patients in the mid-septal as compared with the apical group displayed predominantly positive QRS in lead V6 (62.3 vs. 4.1%, P < 0.001), predominantly positive QRS in any of the inferior leads (53.8 vs. 4.1%, P < 0.001), and a QR pattern in lead aVL (53.3 vs. 3.3%, P < 0.001). These ECG correlates were incorporated in a stepwise algorithm with total sensitivity of 87% and specificity of 90% for the identification of a mid-septal lead location. CONCLUSION: A mid-septal lead location may be identified using a simple stepwise algorithm, based on the presence of positive QRS in lead V6, positive QRS in any of the inferior leads, and a QR pattern in lead aVL.

The CINCH-FMR postmarket registry: Real-world long-term outcomes with percutaneous mitral valve repair with the Carillon Mitral Contour System®.

BACKGROUND: The Carillon® Mitral Contour System® has been studied in 4 prospective controlled studies in the treatment of functional mitral regurgitation (FMR) where it has been found to reduce mitral regurgitation, reduce left ventricular and atrial volumes, and be associated with improvements in clinical parameters. AIMS: The CINCH post-market registry is designed to evaluate immediate, mid-term and long-term outcomes from a post-approval study of the Carillon® device evaluated in real-world practice. METHODS: The CINCH post-market registry is a single-arm study of percutaneous mitral annuloplasty with the Carillon device in patients with functional (secondary) mitral regurgitation and symptomatic congestive heart failure when utilized in real-world conditions. Patient selection, echocardiographic hemodynamic measurements, and patient follow-up requirements were performed per standard of care at each institution. RESULTS: A total of 101 patients treated with the Carillon device at 13 sites in Germany were enrolled in the CINCH registry. The mean age was 75 ± 9 years, 57 % were male, and patient presentation included primarily NYHA class III (69 %) with MR grade 3 (68 %). Over 5 years of follow-up, all-cause mortality was 40.1 %, the incidence of HFH was 53.9 %, and the composite outcome of HFH or death was 66.4 %. At each follow-up interval through 5 years, statistically significant reductions in NYHA class (p < 0.05) and MR grade (p < 0.01) were reported. CONCLUSIONS: In this "real world" registry of the Carillon Mitral Contour System, procedural safety and medium-term follow-up outcomes is similar to the outcomes seen in the prospective, controlled clinical trials, despite being used in populations of patients that extend outside of those studied in the trials. The use of this therapy in patients with atrial functional mitral regurgitation, and heart failure with preserved ejection fraction, was notable, since these types of patients were excluded from the prospective, controlled trials. This supports possible additional patient populations who might benefit from this type of mechanical therapy. The safety profile of this therapy in this registry and in the earlier trials may support a potential role in earlier forms of secondary mitral regurgitation.

Optimal timing of invasive angiography in stable non-ST-elevation myocardial infarction: the Leipzig Immediate versus early and late PercutaneouS coronary Intervention triAl in NSTEMI (LIPSIA-NSTEMI Trial).

AIMS: The optimal timing of intervention in non-ST-elevation myocardial infarction (NSTEMI) remains uncertain. The aim of this multicentre trial was to assess whether an immediate invasive approach is superior to an early invasive or a selective invasive approach with respect to reduction of large infarction. METHODS AND RESULTS: Patients with NSTEMI were randomized to either an immediate (<2 h after randomization; n= 201), an early (10-48 h after randomization; n= 200), or a selective invasive approach with high invasive percentage (n= 201). The primary outcome was the peak creatine kinase (CK)-myocardial band (MB) activity during index hospitalization; key secondary clinical endpoints were the composite of (i) death and non-fatal infarction; (ii) death, non-fatal infarction, and refractory ischaemia; (iii) death, non-fatal infarction, refractory ischaemia, and rehospitalization for unstable angina within 6 months. The median time from randomization to angiography was 1.1 h in the immediate vs. 18.6 h in the early and 67.2 h in the selective invasive group (P< 0.001). There was no significant difference in the peak CK-MB activity between groups. The key secondary clinical endpoints were similar between groups at 6-month follow-up: death and infarction: 21.0 vs. 16.0 vs. 14.5%; P= 0.17; death, infarction, refractory ischaemia: 20.9 vs. 21.5 vs. 22.0%; P= 0.98; death, infarction, refractory ischaemia, rehospitalization: 26.0 vs. 26.5 vs. 24.5%; P= 0.91, respectively. CONCLUSIONS: In NSTEMI patients, an immediate invasive approach does not offer an advantage over an early or a selective invasive approach with respect to large myocardial infarctions as defined by peak CK-MB levels, which is supported by similar clinical outcomes. ClinicalTrials.gov NCT00402675.

Toward Fabrication of Devices Based on Graphene/Oxide Multilayers.

Owing to its high electrical conductivity, low density, and flexibility, graphene has great potential for use as a building block in a wide range of applications from nanoelectronics to biosensing and high-frequency devices. For many device applications, it is required to deposit dielectric materials on graphene at high temperatures and in ambient oxygen. This has been proven to be highly challenging because these conditions cause significant degradation in graphene. In this work, we investigate the degradation of graphene at elevated temperatures in an oxygen atmosphere and possible protection mechanisms to enable the growth of oxide thin films on graphene at higher temperatures. We show that coating graphene with self-assembled monolayers of hexamethyldisilazane (HMDS) prior to a high-temperature deposition can significantly reduce the damage induced. Furthermore, a graphene sample treated with HMDS displayed a weaker doping effect due to weak interaction with oxygen species than bare graphene, and a much slower rate of electrical resistance degradation was exhibited during annealing. Thus, it is a promising approach that could enable the deposition of metal oxide materials on graphene at high temperatures without significant degradation in graphene quality, which is critical for a wide range of applications.

REACT DX registry: Real world REACTion to atrial high rate episodes detected in implantable cardioverter-defibrillator recipients with a DX lead.

BACKGROUND: Atrial fibrillation (AF) is associated with significant morbidity and is predicted by atrial high rate events. The early detection of AF is paramount to timely interventions to reduce the morbidity of AF. The DX ICD system combined with Home Monitoring® allows for continuous atrial rhythm monitoring without the need for a dedicated atrial lead. OBJECTIVE: To establish the reaction to and timing of reactions to the detection of atrial high rate episodes (AHRE). METHODS: A prospective cohort of DX ICD systems was followed up and the response to AHREs was collected and evaluated. RESULTS: A total of 234 patients were enrolled; an AHRE ⩾ 6 min was detected in 13.7% of patients (n= 32) within a mean follow-up duration of 16 months. A high rate of oral anticoagulation (OAC) prescription was seen with the detection of AHREs in patients with a not-low risk CHA2DS2-VASc score. There was a delay in this prescription highlighting the potential to improve the timeliness of patient care in this group of patients. CONCLUSIONS: The DX ICD system provides rapid and ongoing atrial rhythm monitoring such that physicians are rapidly aware of AHRE without the need for a dedicated atrial lead, but local protocols are needed to improve the response time of anti-coagulation prescription.

Use of the Wearable Cardioverter-Defibrillator Among Patients With Myocarditis and Reduced Ejection Fraction or Ventricular Tachyarrhythmia: Data From a Multicenter Registry.

Background Data on the use of the wearable cardioverter-defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin-converting enzyme inhibitors (62.5%), angiotensin-receptor-neprilysin inhibitor (22.9%), aldosterone-antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%-45%) and increased to 48% (39%-55%) over long-term follow-up (P<0.001). The median BNP (brain natriuretic peptide) level at baseline was 1702 pg/mL (565-3748) and decreased to 188 pg/mL (26-348) over long-term follow-up (P=0.022). The mean wear time was 79.7±52.1 days and 21.0±4.9 hours per day. Arrhythmic event rates documented by the WCD were 9.7% for nonsustained ventricular tachycardia, 6.5% for sustained ventricular tachycardia, and 0% for ventricular fibrillation. Subsequently, 2.4% of patients experienced an appropriate WCD shock. The rate of inappropriate WCD shocks was 0.8%. All 3 patients with appropriate WCD shock had experienced ventricular tachycardia/ventricular fibrillation before WCD prescription, with only 1 patient showing a left ventricular ejection fraction <35%. Conclusions Patients with myocarditis and risk for occurrence of ventricular tachyarrhythmia may benefit from WCD use. Prior ventricular arrhythmia might appear as a better risk predictor than a reduced left ventricular ejection fraction <35% in this population.

Graphene Sensor Arrays for Rapid and Accurate Detection of Pancreatic Cancer Exosomes in Patients' Blood Plasma Samples.

Biosensors based on graphene field effect transistors (GFETs) have the potential to enable the development of point-of-care diagnostic tools for early stage disease detection. However, issues with reproducibility and manufacturing yields of graphene sensors, but also with Debye screening and unwanted detection of nonspecific species, have prevented the wider clinical use of graphene technology. Here, we demonstrate that our wafer-scalable GFETs array platform enables meaningful clinical results. As a case study of high clinical relevance, we demonstrate an accurate and robust portable GFET array biosensor platform for the detection of pancreatic ductal adenocarcinoma (PDAC) in patients' plasma through specific exosomes (GPC-1 expression) within 45 min. In order to facilitate reproducible detection in blood plasma, we optimized the analytical performance of GFET biosensors via the application of an internal control channel and the development of an optimized test protocol. Based on samples from 18 PDAC patients and 8 healthy controls, the GFET biosensor arrays could accurately discriminate between the two groups while being able to detect early cancer stages including stages 1 and 2. Furthermore, we confirmed the higher expression of GPC-1 and found that the concentration in PDAC plasma was on average more than 1 order of magnitude higher than in healthy samples. We found that these characteristics of GPC-1 cancerous exosomes are responsible for an increase in the number of target exosomes on the surface of graphene, leading to an improved signal response of the GFET biosensors. This GFET biosensor platform holds great promise for the development of an accurate tool for the rapid diagnosis of pancreatic cancer.

Clinical efficacy of left ventricular pacing vector programmability in cardiac resynchronization therapy defibrillator patients for management of phrenic nerve stimulation and/or elevated left ventricular pacing thresholds: insights from the Efface Phrenic Stim study.

AIMS: Elevated left ventricular (LV) pacing thresholds or phrenic nerve stimulation (PNS) might be possible reasons for absence of continuous and effective biventricular stimulation. This study investigated the benefit and clinical efficacy of the ability to choose one out of three different LV pacing vectors for the management of suboptimal LV pacing thresholds and PNS. METHODS AND RESULTS: This prospective, observational multicentre study enrolled 132 patients (Pts) implanted with a cardiac resynchronization therapy defibrillator, that offers three LV pacing vectors: (i) Bipolar; (ii) LVtip ↔ RVcoil; (iii) LVring ↔ RVcoil (RV = right ventricular). Left ventricular pacing thresholds and PNS thresholds were obtained in sitting and left lateral body position for all programmable LV pacing vectors at hospital discharge and follow up (FU). In 97%, a bipolar transvenous LV lead was successfully implanted. In 87% of Pts at least one acceptable pacing vector could be identified that provides good pacing threshold (≤ 2.5 V at 5 ms) and acceptable margin to PNS (≥ 2:1). This is an increase of 18% compared with conventional bipolar systems (74%) with two LV vectors and of 25% compared with unipolar systems (70%). The LVtip ↔ RVcoil vector provided the best LV pacing thresholds, but the highest rate of PNS. CONCLUSIONS: The programmability of LV pacing vectors is a powerful feature to avoid PNS and obtain acceptable LV pacing thresholds. In order to retain reprogramming options for LV vectors during FU, LV pacing leads with at least two electrodes should be chosen whenever possible.

Real life experience with the wearable cardioverter-defibrillator in an international multicenter Registry.

Patients at high risk for sudden cardiac death (SCD) may benefit from wearable cardioverter defibrillators (WCD) by avoiding immediate implantable cardioverter defibrillator (ICD) implantation. Different factors play an important role including patient selection, compliance and optimal drug treatment. We aimed to present real world data from 4 centers from Germany and Switzerland. Between 04/2012 and 03/2019, 708 patients were included in this registry. Patients were followed up over a mean time of 28 ± 35.5 months. Outcome data including gender differences and different etiologies of cardiomyopathy were analyzed. Out of 708 patients (81.8% males, mean age 61.0 ± 14.6), 44.6% of patients had non-ischemic cardiomyopathy, 39.8% ischemic cardiomyopathy, 7.9% myocarditis, 5.4% prior need for ICD explantation and 2.1% channelopathy. The mean wear time of WCD was 21.2 ± 4.3 h per day. In 46% of patients, left ventricular ejection fraction (LVEF) was > 35% during follow-up. The younger the patient was, the higher the LVEF and the lower the wear hours per day were. The total shock rate during follow-up was 2.7%. Whereas an appropriate WCD shock was documented in 16 patients (2.2%), 3 patients received an inappropriate ICD shock (0.5%). During follow-up, implantation of a cardiac implantable electronic device was carried out in 34.5% of patients. When comparing German patients (n = 516) to Swiss patients (n = 192), Swiss patients presented with longer wear days (70.72 ± 49.47 days versus 58.06 ± 40.45 days; p = 0.001) and a higher ICD implantation rate compared to German patients (48.4% versus 29.3%; p = 0.001), although LVEF at follow-up was similar between both groups. Young age is a negative independent predictor for the compliance in this large registry. The most common indication for WCD was non-ischemic cardiomyopathy followed by ischemic cardiomyopathy. The compliance rate was generally high with a decrease of wear hours per day at younger age. Slight differences were found between Swiss and German patients, which might be related to differences in mentality for ICD implantation.

Detection of Glial Fibrillary Acidic Protein in Patient Plasma Using On-Chip Graphene Field-Effect Biosensors, in Comparison with ELISA and Single-Molecule Array.

Glial fibrillary acidic protein (GFAP) is a discriminative blood biomarker for many neurological diseases, such as traumatic brain injury. Detection of GFAP in buffer solutions using biosensors has been demonstrated, but accurate quantification of GFAP in patient samples has not been reported, yet in urgent need. Herein, we demonstrate a robust on-chip graphene field-effect transistor (GFET) biosensing method for sensitive and ultrafast detection of GFAP in patient plasma. Patients with moderate-severe traumatic brain injuries, defined by the Mayo classification, are recruited to provide plasma samples. The binding of target GFAP with the specific antibodies that are conjugated on a monolayer GFET device triggers the shift of its Dirac point, and this signal change is correlated with the GFAP concentration in the patient plasma. The limit of detection (LOD) values of 20 fg/mL (400 aM) in buffer solution and 231 fg/mL (4 fM) in patient plasma have been achieved using this approach. In parallel, for the first time, we compare our results to the state-of-the-art single-molecule array (Simoa) technology and the classic enzyme-linked immunosorbent assay (ELISA) for reference. The GFET biosensor shows competitive LOD to Simoa (1.18 pg/mL) and faster sample-to-result time (<15 min), and also it is cheaper and more user-friendly. In comparison to ELISA, GFET offers advantages of total detection time, detection sensitivity, and simplicity. This GFET biosensing platform holds high promise for the point-of-care diagnosis and monitoring of traumatic brain injury in GP surgeries and patient homes.

On-chip integrated graphene aptasensor with portable readout for fast and label-free COVID-19 detection in virus transport medium.

Graphene field-effect transistor (GFET) biosensors exhibit high sensitivity due to a large surface-to-volume ratio and the high sensitivity of the Fermi level to the presence of charged biomolecules near the surface. For most reported GFET biosensors, bulky external reference electrodes are used which prevent their full-scale chip integration and contribute to higher costs per test. In this study, GFET arrays with on-chip integrated liquid electrodes were employed for COVID-19 detection and functionalized with either antibody or aptamer to selectively bind the spike proteins of SARS-CoV-2. In the case of the aptamer-functionalized GFET (aptasensor, Apt-GFET), the limit-of-detection (LOD) achieved was about 103 particles per mL for virus-like particles (VLPs) in clinical transport medium, outperforming the Ab-GFET biosensor counterpart. In addition, the aptasensor achieved a LOD of 160 aM for COVID-19 neutralizing antibodies in serum. The sensors were found to be highly selective, fast (sample-to-result within minutes), and stable (low device-to-device signal variation; relative standard deviations below 0.5%). A home-built portable readout electronic unit was employed for simultaneous real-time measurements of 12 GFETs per chip. Our successful demonstration of a portable GFET biosensing platform has high potential for infectious disease detection and other health-care applications.

Enhancing Structural Properties and Performance of Graphene-Based Devices Using Self-Assembled HMDS Monolayers.

The performance of graphene devices is often limited by defects and impurities induced during device fabrication. Polymer residue left on the surface of graphene after photoresist processing can increase electron scattering and hinder electron transport. Furthermore, exposing graphene to plasma-based processing such as sputtering of metallization layers can increase the defect density in graphene and alter the device performance. Therefore, the preservation of the high-quality surface of graphene during thin-film deposition and device manufacturing is essential for many electronic applications. Here, we show that the use of self-assembled monolayers (SAMs) of hexamethyldisilazane (HMDS) as a buffer layer during the device fabrication of graphene can significantly reduce damage, improve the quality of graphene, and enhance device performance. The role of HMDS has been systematically investigated using surface analysis techniques and electrical measurements. The benefits of HMDS treatment include a significant reduction in defect density compared with as-treated graphene and more than a 2-fold reduction of contact resistance. This surface treatment is simple and offers a practical route for improving graphene device interfaces, which is important for the integration of graphene into functional devices such as electronics and sensor devices.