Multiparametric MEMS Biosensors With Integrated Impedance Spectroscopy and Gravimetric Measurements for Water Toxicity Sensing

Author(s):  
Fei Liu ◽  
Fang Li ◽  
Ali Khademhosseini ◽  
Ioana Voiculescu

This paper presents the design, fabrication and characterization of a novel multiparametric microelectromechanical (MEMS) biosensor based on live mammalian cells with capabilities of sensing the toxicity of field water with minimized false-positive rate. This biosensor combines two biosensing techniques, resonant frequency measurements and electric cell-substrate impedance sensing (ECIS) on a single chip. The sensor is based on the innovative placement of the working microelectrode for ECIS technique as the upper electrode of a quartz crystal microbalance (QCM) resonator. This multiparametric biosensor was characterized with bovine aortic endothelial cells (BAECs). Toxicity tests to study BAECs responsiveness to health-threatening concentrations of ammonia in de-ionized water as a toxicant model will also be presented. The increase of the resonant frequency and decrease of impedance of the biosensor indicated the detachment of cells as a result of toxicant stimulation of ammonia solution. These gravimetric and impedimetric measurements on the same cell monolayer demonstrate that the multiparametric biosensor is able to perform two types of measurements simultaneously and this sensor can successfully be tested with drinking water containing toxicants.

Author(s):  
Fei Liu ◽  
Anis N. Nordin ◽  
Fang Li ◽  
Ioana Voiculescu

Recently, there has been interest to develop biosensors based on live mammalian cells to monitor the toxicity of water. The cell viability after exposure to toxic water can be monitored by electric cell-substrate impedance sensing (ECIS) of the cell membrane. However, these impedance based toxicity sensors can only provide one single sensing endpoint (impedance measurement), and many toxicants cannot be detected at the concentration between Military Exposure Guideline levels and estimated Human Lethal Concentrations. The goal of this paper is to provide a rapid and sensitive sensing platform for long-term water toxicity detection. In this paper a novel multiparametric biosensor with integrated microfluidic channels for water toxicity detection is presented. Toxicity tests to study bovine aortic endothelial cells (BAECs) responsiveness to health-threatening concentrations of ammonia in de-ionized (DI) water will be presented. We demonstrated the BAECs can rapidly respond to ammonia concentrations between the military exposure guideline of 2mM and human lethal concentration of 55mM. The successful testing of water toxicity by simultaneous gravimetric and impedimetric measurements indicates that the multiparametric biosensor platform is able to perform rapid and sensitive detection of water toxicity and minimize the false-positive rate.


Author(s):  
Fei Liu ◽  
Fang Li ◽  
David C. Spray ◽  
Anis Nurashikin Nordin ◽  
Ioana Voiculescu

This paper presents the fabrication and testing of a novel microelectromechanical (MEMS) biosensor based on live cells. The biosensor combines two biosensing techniques; resonant frequency measurements and electric cell-substrate impedance sensing (ECIS) on a single device. The sensor is based on the innovative placement of the working microelectrode for ECIS technique as the upper electrode of a quartz crystal microbalance (QCM) resonator. This hybrid biosensor was tested with bovine aortic endothelial cells with different seeding densities. The cell attachment and spreading was monitored with both sensors; the QCM and the ECIS technique. After the cells form a monolayer the values of the impedance and resonant frequency measurements are constant. The optimal cell seeding density with minimal time required to attach and form a monolayer was observed to be 1.5×104 cells/cm2. This biosensor monitors the cells attachment and viability and could be used for screening toxicants in drinking water.


Micromachines ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 439 ◽  
Author(s):  
Ioana Voiculescu ◽  
Masaya Toda ◽  
Naoki Inomata ◽  
Takahito Ono ◽  
Fang Li

This review presents several sensors with dimensions at the nano- and micro-scale used for biological applications. Two types of cantilever beams employed as highly sensitive temperature sensors with biological applications will be presented. One type of cantilever beam is fabricated from composite materials and is operated in the deflection mode. In order to achieve the high sensitivity required for detection of heat generated by a single mammalian cell, the cantilever beam temperature sensor presented in this review was microprocessed with a length at the microscale and a thickness in the nanoscale dimension. The second type of cantilever beam presented in this review was operated in the resonant frequency regime. The working principle of the vibrating cantilever beam temperature sensor is based on shifts in resonant frequency in response to temperature variations generated by mammalian cells. Besides the cantilever beam biosensors, two biosensors based on the electric cell-substrate impedance sensing (ECIS) used to monitor mammalian cells attachment and viability will be presented in this review. These ECIS sensors have dimensions at the microscale, with the gold films used for electrodes having thickness at the nanoscale. These micro/nano biosensors and their mammalian cell applications presented in the review demonstrates the diversity of the biosensor technology and applications.


2002 ◽  
Vol 41 (01) ◽  
pp. 37-41 ◽  
Author(s):  
S. Shung-Shung ◽  
S. Yu-Chien ◽  
Y. Mei-Due ◽  
W. Hwei-Chung ◽  
A. Kao

Summary Aim: Even with careful observation, the overall false-positive rate of laparotomy remains 10-15% when acute appendicitis was suspected. Therefore, the clinical efficacy of Tc-99m HMPAO labeled leukocyte (TC-WBC) scan for the diagnosis of acute appendicitis in patients presenting with atypical clinical findings is assessed. Patients and Methods: Eighty patients presenting with acute abdominal pain and possible acute appendicitis but atypical findings were included in this study. After intravenous injection of TC-WBC, serial anterior abdominal/pelvic images at 30, 60, 120 and 240 min with 800k counts were obtained with a gamma camera. Any abnormal localization of radioactivity in the right lower quadrant of the abdomen, equal to or greater than bone marrow activity, was considered as a positive scan. Results: 36 out of 49 patients showing positive TC-WBC scans received appendectomy. They all proved to have positive pathological findings. Five positive TC-WBC were not related to acute appendicitis, because of other pathological lesions. Eight patients were not operated and clinical follow-up after one month revealed no acute abdominal condition. Three of 31 patients with negative TC-WBC scans received appendectomy. They also presented positive pathological findings. The remaining 28 patients did not receive operations and revealed no evidence of appendicitis after at least one month of follow-up. The overall sensitivity, specificity, accuracy, positive and negative predictive values for TC-WBC scan to diagnose acute appendicitis were 92, 78, 86, 82, and 90%, respectively. Conclusion: TC-WBC scan provides a rapid and highly accurate method for the diagnosis of acute appendicitis in patients with equivocal clinical examination. It proved useful in reducing the false-positive rate of laparotomy and shortens the time necessary for clinical observation.


1993 ◽  
Vol 32 (02) ◽  
pp. 175-179 ◽  
Author(s):  
B. Brambati ◽  
T. Chard ◽  
J. G. Grudzinskas ◽  
M. C. M. Macintosh

Abstract:The analysis of the clinical efficiency of a biochemical parameter in the prediction of chromosome anomalies is described, using a database of 475 cases including 30 abnormalities. A comparison was made of two different approaches to the statistical analysis: the use of Gaussian frequency distributions and likelihood ratios, and logistic regression. Both methods computed that for a 5% false-positive rate approximately 60% of anomalies are detected on the basis of maternal age and serum PAPP-A. The logistic regression analysis is appropriate where the outcome variable (chromosome anomaly) is binary and the detection rates refer to the original data only. The likelihood ratio method is used to predict the outcome in the general population. The latter method depends on the data or some transformation of the data fitting a known frequency distribution (Gaussian in this case). The precision of the predicted detection rates is limited by the small sample of abnormals (30 cases). Varying the means and standard deviations (to the limits of their 95% confidence intervals) of the fitted log Gaussian distributions resulted in a detection rate varying between 42% and 79% for a 5% false-positive rate. Thus, although the likelihood ratio method is potentially the better method in determining the usefulness of a test in the general population, larger numbers of abnormal cases are required to stabilise the means and standard deviations of the fitted log Gaussian distributions.


2019 ◽  
Author(s):  
Amanda Kvarven ◽  
Eirik Strømland ◽  
Magnus Johannesson

Andrews & Kasy (2019) propose an approach for adjusting effect sizes in meta-analysis for publication bias. We use the Andrews-Kasy estimator to adjust the result of 15 meta-analyses and compare the adjusted results to 15 large-scale multiple labs replication studies estimating the same effects. The pre-registered replications provide precisely estimated effect sizes, which do not suffer from publication bias. The Andrews-Kasy approach leads to a moderate reduction of the inflated effect sizes in the meta-analyses. However, the approach still overestimates effect sizes by a factor of about two or more and has an estimated false positive rate of between 57% and 100%.


2019 ◽  
Author(s):  
Stephen D Benning ◽  
Edward Smith

The emergent interpersonal syndrome (EIS) approach conceptualizes personality disorders as the interaction among their constituent traits to predict important criterion variables. We detail the difficulties we have experienced finding such interactive predictors in our empirical work on psychopathy, even when using uncorrelated traits that maximize power. Rather than explaining a large absolute proportion of variance in interpersonal outcomes, EIS interactions might explain small amounts of variance relative to the main effects of each trait. Indeed, these interactions may necessitate samples of almost 1,000 observations for 80% power and a false positive rate of .05. EIS models must describe which specific traits’ interactions constitute a particular EIS, as effect sizes appear to diminish as higher-order trait interactions are analyzed. Considering whether EIS interactions are ordinal with non-crossing slopes, disordinal with crossing slopes, or entail non-linear threshold or saturation effects may help researchers design studies, sampling strategies, and analyses to model their expected effects efficiently.


Electronics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1894
Author(s):  
Chun Guo ◽  
Zihua Song ◽  
Yuan Ping ◽  
Guowei Shen ◽  
Yuhei Cui ◽  
...  

Remote Access Trojan (RAT) is one of the most terrible security threats that organizations face today. At present, two major RAT detection methods are host-based and network-based detection methods. To complement one another’s strengths, this article proposes a phased RATs detection method by combining double-side features (PRATD). In PRATD, both host-side and network-side features are combined to build detection models, which is conducive to distinguishing the RATs from benign programs because that the RATs not only generate traffic on the network but also leave traces on the host at run time. Besides, PRATD trains two different detection models for the two runtime states of RATs for improving the True Positive Rate (TPR). The experiments on the network and host records collected from five kinds of benign programs and 20 famous RATs show that PRATD can effectively detect RATs, it can achieve a TPR as high as 93.609% with a False Positive Rate (FPR) as low as 0.407% for the known RATs, a TPR 81.928% and FPR 0.185% for the unknown RATs, which suggests it is a competitive candidate for RAT detection.


2021 ◽  
pp. 103985622110286
Author(s):  
Tracey Wade ◽  
Jamie-Lee Pennesi ◽  
Yuan Zhou

Objective: Currently eligibility for expanded Medicare items for eating disorders (excluding anorexia nervosa) require a score ⩾ 3 on the 22-item Eating Disorder Examination-Questionnaire (EDE-Q). We compared these EDE-Q “cases” with continuous scores on a validated 7-item version of the EDE-Q (EDE-Q7) to identify an EDE-Q7 cut-off commensurate to 3 on the EDE-Q. Methods: We utilised EDE-Q scores of female university students ( N = 337) at risk of developing an eating disorder. We used a receiver operating characteristic (ROC) curve to assess the relationship between the true-positive rate (sensitivity) and the false-positive rate (1-specificity) of cases ⩾ 3. Results: The area under the curve showed outstanding discrimination of 0.94 (95% CI: .92–.97). We examined two specific cut-off points on the EDE-Q7, which included 100% and 87% of true cases, respectively. Conclusion: Given the EDE-Q cut-off for Medicare is used in conjunction with other criteria, we suggest using the more permissive EDE-Q7 cut-off (⩾2.5) to replace use of the EDE-Q cut-off (⩾3) in eligibility assessments.


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