3D nanogap interdigitated electrode array biosensors.

Three-dimensional interdigitated electrodes (IDEs) have been investigated as sensing elements for biosensors. Electric field and current density were simulated in the vicinity of these electrodes as a function of the electrode width, gap, and height to determine the optimum geometry. Both the height and the gap between the electrodes were found to have significant effect on the magnitude and distribution of the electric field and current density near the electrode surface, while the width of the electrodes was found to have a smaller effect on field strength and current density. IDEs were fabricated based on these simulations and their performance tested by detecting C-reactive protein (CRP), a stress-related protein and an important biomarker for inflammation, cardiovascular disease risk indicator, and postsurgical recuperation. CRP-specific antibodies were immobilized on the electrode surface and the formation of an immunocomplex (IC) with CRP was monitored. Electrochemical impedance spectroscopy (EIS) was employed as the detection technique. EIS data at various concentrations (1 pg/mL to 10 microg/mL) of CRP spiked in buffer or diluted human serum was collected and fitted into an equivalent electrical circuit model. Change in resistance was found to be the parameter most sensitive to change in CRP concentration. The sensor response was linear from 0.1 ng/mL to 1 microg/mL in both buffer and 5% human serum samples. The CRP samples were validated using a commercially available ELISA for CRP detection. Hence, the viability of IDEs and EIS for the detection of serum biomarkers was established without using labeled or probe molecules.

Electrical nanowell diagnostics sensors for rapid and ultrasensitive detection of prostate-specific antigen.

AIM: Alumina nanowell based disposable diagnostic biosensor for detecting and quantifying levels of prostate-specific antigen (PSA) from human serum has been designed, fabricated and tested. MATERIALS & METHODS: The biosensors were designed by integrating nanoporous alumina membranes onto printed circuit board platforms, resulting in the generation of high-density nanowell arrays with gold base electrodes. The size and density of the nanowells were leveraged toward achieving sieving action for size-based exclusion of nonspecific molecules and size-based confinement of the target PSA molecules. RESULTS & CONCLUSION: We demonstrated PSA detection between 0.01 and 1000 ng/ml and detection and quantification of PSA from a 17 patient cohort validated using the Beckman Access system with >95% correlation.

Novel Nanomonitor ultra-sensitive detection of troponin T.

BACKGROUND: Troponin is the preferred biomarker for diagnosing myocardial infarction. Point of care devices have not matched the sensitivity of laboratory-based methods for measuring troponin. The Nanomonitor is a novel point-of-care device that uses the change in electrical impedance that occurs when a biomarker binds to its antibody, which is then correlated to the concentration of the target biomarker. METHODS: Performance characteristics of the Nanomonitor were evaluated and compared to a standard laboratory-based method. RESULTS: The limit of detection of the Nanomonior for troponin T was 0.0088ng/l. Total imprecission was 2.38% and 0.85% at troponin T concentrations of 73ng/l and 1800ng/l. The functional sensitivity (10% coeffecient of variation) was 0.329ng/l. The linear regression had a slope of 0.996 (95% confidence interval, 0.991, 1.002), r=1.00, and an intercept of 15.88ng/l (95% confidence interval, -68.39ng/l, 100.15ng/l). The mean difference between the assays was -7.54ng/l, determined by Bland-Altman analysis. CONCLUSION: The Nanomonitor preliminary results have favorable performance characteristics for detecting troponin T in patient blood, provide results in 15min, and are portable. More research is needed.

Portable nanoporous electrical biosensor for ultrasensitive detection of Troponin-T.

AIM: To demonstrate the design, fabrication and testing of a portable, label-free biosensor for ultrasensitive detection of the cardiac Troponin-T (cTnT) from patient blood. MATERIALS & METHODS: The biosensor is comprised of a nanoporous membrane integrated on to a microelectrode sensor platform for nanoconfinement effects. Charge perturbations due to antigen binding are recorded as impedance changes using electrochemical impedance spectroscopy. RESULTS: The measured impedance change is used to quantitatively determine the cTnT concentration from the tested sample. We were successful in detecting and quantifying cardiac Troponin-T from a 40-patient cohort. The limit of detection was 0.01 pg/ml. CONCLUSION: This novel technology has promising preliminary results for rapid and sensitive detection of cTnT.

Evaluating an insulin infusion protocol in an acute care setting.

OBJECTIVE: The objective of the present study was to evaluate the adherence, safety, and effectiveness of a paper versus an electronic insulin infusion protocol. DESIGN: This quasi-experimental implementation study compared experimental and control groups using a nonrandomized prospective cohort design. SETTING: The study was performed at 2 surgical units within a federal tertiary care teaching hospital. SAMPLE: Fifty-eight registered nurses volunteered. METHODS: We compared time intervals using electronic time stamps from glucometers and insulin infusion devices to measure protocol adherence. We assessed perceived adherence using a nurse survey, and, to evaluate safety, we reviewed each paper protocol infusion calculation for correctness. FINDINGS: Median times from blood glucose acquisition to infusion rate adjustment did not differ significantly between groups (P = .215). The majority of infusions (96.6%) had glucose acquisition times within the acceptable range. Median values of time to next "glucose due" did not differ significantly (P = .88), and relative variation in median glucose reporting times did not differ significantly between groups (P = .16). Evaluation of 877 paper protocol entries demonstrated a 10.7% (n = 94) calculation error rate. Registered nurses within the electronic group reported greater ease in balancing workload when compared with paper protocol use (P = .03). Attitudes did not differ significantly between groups in areas of determining infusion adjustment, bolus insulin dose, next glucose due, ease of access, understanding protocol, or overall satisfaction. CONCLUSIONS: This study demonstrates that one can adhere to an insulin infusion protocol, regardless of the format (paper or electronic), in the medical-surgical setting. Our results suggest there are safety and nurse workload benefits when an electronic protocol was used. IMPLICATIONS: Adherence, safety, and effectiveness can be achieved when using insulin infusion in the medical-surgical setting.

Impact of combination medical therapy on mortality in vascular surgery patients.

BACKGROUND: Th use of beta-blockers or statins has been associated with decreased mortality after noncardiac surgery. There are no prior perioperative studies of concurrent use of other cardioprotective drugs. OBJECTIVE: To ascertain whether combinations of aspirin, beta-blockers, statins, and/or angiotensin-converting enzyme (ACE) inhibitors were associated with decreased mortality 6 months after vascular surgery. PATIENTS AND DESIGN: We performed a retrospective cohort study on the 3020 patients who underwent vascular surgery between January 1998 and March 2005 at 5 regional Veterans Affairs (VA) medical centers. The Cochran-Mantel-Haenszel test was used to assess associations with 6-month all-cause mortality for the combination drug exposures compared to no exposure while adjusting for propensity score. RESULTS: Exposure to all 4 of the study drugs compared to none had a propensity-adjusted relative risk (aRR) of 0.52 (95% confidence interval [CI], 0.26-1.01; P = 0.052), number needed to treat (NNT) 19; 3 drugs vs. none, aRR 0.60 (95% CI, 0.38-0.95; P = 0.030), NNT 38; 2 drugs vs. none, aRR 0.68 (95% CI, 0.46-0.99; P = 0.043), NNT 170; and 1 drug vs. none, aRR 0.88 (95% CI, 0.63-1.22; P = 0.445). ACE inhibitor exposure was common in all combinations. CONCLUSIONS: Combination use of 2 to 3 study drugs, some of which included ACE inhibitors, was associated with decreased mortality after vascular surgery. Combination use of all 4 study drugs was not statistically significant due to the small number of events in this group. Further prospective studies of combination perioperative aspirin, beta-blockers, statins, and ACE inhibitors are warranted.

Association of ambulatory use of statins and beta-blockers with long-term mortality after vascular surgery.

BACKGROUND: The use of drugs to improve postoperative outcomes has focused on short-term end points and centered on beta-blockers. Emerging evidence suggests statins may also improve postoperative outcomes. OBJECTIVE: We sought to ascertain if the ambulatory use of statins and/or beta-blockers was associated with a reduction in long-term mortality after vascular surgery. DESIGN: Retrospective cohort study with a median follow-up of 2.7 years. SETTING: Regional multicenter study at Veterans Affairs medical centers. PATIENTS: Three thousand and sixty-two patients presenting for vascular surgery. MEASUREMENTS: Patients were categorized as using statins or beta-blockers if they filled a prescription for the study drug within 30 days of surgery. Survival analyses, propensity score methods, and stratifications by the revised cardiac risk index (RCRI) were performed. RESULTS: Propensity-adjusted ambulatory use of statins and beta-blockers was associated with a reduction in mortality over the study period compared with nonuse of these medications hazard ratio [HR] = 0.78 [95% CI: 0.67-0.92], P = .0021, and number needed to treat (NNT) = 22 for statins; HR = 0.84 [95% CI: 0.73-0.96], P = .0106, and NNT = 30 for beta-blockers. In addition, for propensity-adjusted use of both statins and beta-blockers compared with neither the HR was 0.56 [95% CI: 0.42-0.74] P < .0001, and NNT was 9. The RCRI confirmed combination statin and beta-blocker use was beneficial at all levels of risk. Use of the combination study drugs by the highest-risk patients was associated with a 33% decrease in mortality after 2 years (P = .0106). CONCLUSIONS: The use of ambulatory statins alone or in combination with beta-blockers is associated with a reduction in long-term mortality after vascular surgery, and combination use benefits patients at all levels of risk.