scholarly journals Graphene FET Sensors for Alzheimer’s Disease Protein Biomarker Clusterin Detection

Proceedings ◽  
2020 ◽  
Vol 60 (1) ◽  
pp. 14
Author(s):  
Theodore Bungon ◽  
Carrie Haslam ◽  
Samar Damiati ◽  
Benjamin O’Driscoll ◽  
Toby Whitley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Electrical Measurements ◽  
Protein Biomarker ◽  
Sio2 Substrate ◽  
Lift Off ◽  
Graphene Fet

We report on the fabrication and characterisation of Graphene field-effect transistor (GFET) Biosensors for detecting clusterin, a prominent protein biomarker of Alzheimer’s disease (AD). There are approximately 54 million people currently living with dementia worldwide and this is expected to rise to 130 million by 2050. Although there are over 400 different types of dementia, AD is the most common type, affecting between 50–75% of those diagnosed with dementia. Diagnosis of AD can take up to 2 years currently using MRI, PET, CT scans and memory tests. There is, therefore, an urgent need to develop low-cost, accurate, non-invasive and point-of-care (PoC) sensors for early diagnosis of AD. The GFET sensors we are developing to address this challenge were fabricated on Si/SiO2 substrate through processes of photolithographic patterning and metal lift-off techniques with evaporated chromium and sputtered gold contacts. Raman Spectroscopy was performed on the devices to determine the quality of the graphene. The GFETs were annealed to improve their performance before the channels were functionalized by immobilising the graphene surface with a linker molecule and anti-clusterin antibody. The detection was achieved through the binding reaction between the antibody and varying concentrations of clusterin antigen from 1 pg/mL to 1 ng/mL. The GFETs were characterized using 4-probe direct current (DC) electrical measurements which demonstrated a limit of detection of the biosensors to be below 1 pg/mL.

scholarly journals Graphene FET Sensors for Alzheimer’s Disease Protein Biomarker Clusterin Detection

2021 ◽  
Vol 8 ◽  
Author(s):  
Theodore Bungon ◽  
Carrie Haslam ◽  
Samar Damiati ◽  
Benjamin O’Driscoll ◽  
Toby Whitley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Limit Of Detection ◽  
Protein Biomarker ◽  
Graphene Field Effect Transistor ◽  
Disease Protein ◽  
Lift Off ◽  
Graphene Fet ◽  
Clusterin Protein ◽  
Linker Molecules

We report on the fabrication and characterisation of graphene field-effect transistor (GFET) biosensors for the detection of Clusterin, a prominent protein biomarker of Alzheimer’s disease (AD). The GFET sensors were fabricated on Si/SiO2 substrate using photolithographic patterning and metal lift-off techniques with evaporated chromium and sputtered gold contacts. Raman Spectroscopy was performed on the devices to determine the quality of the graphene. The GFETs were annealed to improve their performance before the channels were functionalized by immobilising the graphene surface with linker molecules and anti-Clusterin antibodies. Concentration of linker molecules was also independently verified by absorption spectroscopy using the highly collimated micro-beam light of Diamond B23 beamline. The detection was achieved through the binding reaction between the antibody and varying concentrations of Clusterin antigen from 1 to 100 pg/mL, as well as specificity tests using human chorionic gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFETs were characterized using direct current (DC) 4-probe electrical resistance (4-PER) measurements, which demonstrated a limit of detection of the biosensors to be ∼ 300 fg/mL (4 fM). Comparison with back-gated Dirac voltage shifts with varying concentration of Clusterin show 4-PER measurements to be more accurate, at present, and point to a requirement for further optimisation of the fabrication processes for our next generation of GFET sensors. Thus, we have successfully fabricated a promising set of GFET biosensors for the detection of Clusterin protein biomarker. The developed GFET biosensors are entirely generic and also have the potential to be applied to a variety of other disease detection applications such as Parkinson’s, cancer, and cardiovascular.

scholarly journals Rapid and Sensitive Detection of miRNA Based on AC Electrokinetic Capacitive Sensing for Point-of-Care Applications

Sensors ◽  
2021 ◽  
Vol 21 (12) ◽  
pp. 3985
Author(s):  
Nan Wan ◽  
Yu Jiang ◽  
Jiamei Huang ◽  
Rania Oueslati ◽  
Shigetoshi Eda ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Clinical Diagnostics ◽  
Detection Methods ◽  
Capacitive Sensing ◽  
Application Potential ◽  
Mirna Detection ◽  
Mirna 25 ◽  
Low Sensitivity

A sensitive and efficient method for microRNAs (miRNAs) detection is strongly desired by clinicians and, in recent years, the search for such a method has drawn much attention. There has been significant interest in using miRNA as biomarkers for multiple diseases and conditions in clinical diagnostics. Presently, most miRNA detection methods suffer from drawbacks, e.g., low sensitivity, long assay time, expensive equipment, trained personnel, or unsuitability for point-of-care. New methodologies are needed to overcome these limitations to allow rapid, sensitive, low-cost, easy-to-use, and portable methods for miRNA detection at the point of care. In this work, to overcome these shortcomings, we integrated capacitive sensing and alternating current electrokinetic effects to detect specific miRNA-16b molecules, as a model, with the limit of detection reaching 1.0 femto molar (fM) levels. The specificity of the sensor was verified by testing miRNA-25, which has the same length as miRNA-16b. The sensor we developed demonstrated significant improvements in sensitivity, response time and cost over other miRNA detection methods, and has application potential at point-of-care.

scholarly journals Demonstration of a Label-Free and Low-Cost Optical Cavity-Based Biosensor Using Streptavidin and C-Reactive Protein

Biosensors ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Donggee Rho ◽  
Seunghyun Kim
Keyword(s):  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Optical Cavity ◽  
Sample Volume ◽  
Small Sample ◽  
Label Free ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Cavity Structure

An optical cavity-based biosensor (OCB) has been developed for point-of-care (POC) applications. This label-free biosensor employs low-cost components and simple fabrication processes to lower the overall cost while achieving high sensitivity using a differential detection method. To experimentally demonstrate its limit of detection (LOD), we conducted biosensing experiments with streptavidin and C-reactive protein (CRP). The optical cavity structure was optimized further for better sensitivity and easier fluid control. We utilized the polymer swelling property to fine-tune the optical cavity width, which significantly improved the success rate to produce measurable samples. Four different concentrations of streptavidin were tested in triplicate, and the LOD of the OCB was determined to be 1.35 nM. The OCB also successfully detected three different concentrations of human CRP using biotinylated CRP antibody. The LOD for CRP detection was 377 pM. All measurements were done using a small sample volume of 15 µL within 30 min. By reducing the sensing area, improving the functionalization and passivation processes, and increasing the sample volume, the LOD of the OCB are estimated to be reduced further to the femto-molar range. Overall, the demonstrated capability of the OCB in the present work shows great potential to be used as a promising POC biosensor.

scholarly journals A comparison of resting state EEG and structural MRI for classifying Alzheimer’s disease and mild cognitive impairment

2019 ◽  
Author(s):  
FR Farina ◽  
DD Emek-Savaş ◽  
L Rueda-Delgado ◽  
R Boyle ◽  
H Kiiski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Resting State ◽  
Healthy Aging ◽  
Neurodegenerative Disorder ◽  
Low Cost ◽  
Structural Mri ◽  
Lower Accuracy

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterised by severe cognitive decline and loss of autonomy. AD is the leading cause of dementia. AD is preceded by mild cognitive impairment (MCI). By 2050, 68% of new dementia cases will occur in low- and middle-income countries. In the absence of objective biomarkers, psychological assessments are typically used to diagnose MCI and AD. However, these require specialist training and rely on subjective judgements. The need for low-cost, accessible and objective tools to aid AD and MCI diagnosis is therefore crucial. Electroencephalography (EEG) has potential as one such tool: it is relatively inexpensive (cf. magnetic resonance imaging; MRI) and is portable. In this study, we collected resting state EEG, structural MRI and rich neuropsychological data from older adults (55+ years) with AD, with MCI and from healthy controls (n~60 per group). Our goal was to evaluate the utility of EEG, relative to MRI, for the classification of MCI and AD. We also assessed the performance of combined EEG and behavioural (Mini-Mental State Examination; MMSE) and structural MRI classification models. Resting state EEG classified AD and HC participants with moderate accuracy (AROC=0.76), with lower accuracy when distinguishing MCI from HC participants (AROC=0.67). The addition of EEG data to MMSE scores had no additional value compared to MMSE alone. Structural MRI out-performed EEG (AD vs HC, AD vs MCI: AROCs=1.00; HC vs MCI: AROC=0.73). Resting state EEG does not appear to be a suitable tool for classifying AD. However, EEG classification accuracy was comparable to structural MRI when distinguishing MCI from healthy aging, although neither were sufficiently accurate to have clinical utility. This is the first direct comparison of EEG and MRI as classification tools in AD and MCI participants.

scholarly journals Alzheimer’s Disease Diagnostics Must Be Globally Accessible

2021 ◽  
pp. 1-3
Author(s):  
Nicholas Clute-Reinig ◽  
Suman Jayadev ◽  
Kristoffer Rhoads ◽  
Anne-Laure Le Ny
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Global Health ◽  
Low Cost ◽  
High Income ◽  
Middle Income ◽  
Middle Income Countries ◽  
Disease Diagnostics ◽  
Low And Middle Income

Dementia and Alzheimer’s disease (AD) are global health crises, with most affected individuals living in low- or middle-income countries. While research into diagnostics and therapeutics remains focused exclusively on high-income populations, recent technological breakthroughs suggest that low-cost AD diagnostics may soon be possible. However, as this disease shifts onto those with the least financial and structural ability to shoulder its burden, it is incumbent on high-income countries to develop accessible AD healthcare. We argue that there is a scientific and ethical mandate to develop low-cost diagnostics that will not only benefit patients in low-and middle-income countries but the AD field as a whole.

scholarly journals Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kayoung Kim ◽  
Min-Ji Kim ◽  
Da Won Kim ◽  
Su Yeong Kim ◽  
Steve Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Plasma ◽  
Sensor Array ◽  
Neurodegenerative Disorder ◽  
Limit Of Detection ◽  
Average Accuracy ◽  
Severity Of The Disease ◽  
High Degree ◽  
T Tau

AbstractAlzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, affecting one in ten people aged over 65 years. Despite the severity of the disease, early diagnosis of AD is still challenging due to the low accuracy or high cost of neuropsychological tests and neuroimaging. Here we report clinically accurate and ultrasensitive detection of multiple AD core biomarkers (t-tau, p-tau181, Aβ42, and Aβ40) in human plasma using densely aligned carbon nanotubes (CNTs). The closely packed and unidirectionally aligned CNT sensor array exhibits high precision, sensitivity, and accuracy, evidenced by a low coefficient of variation (<6%), a femtomolar-level limit of detection, and a high degree of recovery (>93.0%). By measuring the levels of t-tau/Aβ42, p-tau181/Aβ42, and Aβ42/Aβ40 in clinical blood samples, the sensor array successfully discriminates the clinically diagnosed AD patients from healthy controls with an average sensitivity of 90.0%, a selectivity of 90.0%, and an average accuracy of 88.6%.

scholarly journals Trimodal Waveguide Demonstration and Its Implementation as a High Order Mode Interferometer for Sensing Application

Sensors ◽  
2019 ◽  
Vol 19 (12) ◽  
pp. 2821 ◽  
Author(s):  
Jhonattan C. Ramirez ◽  
Lucas H. Gabrielli ◽  
Laura M. Lechuga ◽  
Hugo E. Hernandez-Figueroa
Keyword(s):  
Free Spectral Range ◽  
Point Of Care ◽  
Low Cost ◽  
High Order Mode ◽  
Sio2 Substrate ◽  
Polymer Waveguide ◽  
Sensing Applications ◽  
Highly Sensitive ◽  
Different Types ◽  
Mode Order

This work implements and demonstrates an interferometric transducer based on a trimodal optical waveguide concept. The readout signal is generated from the interference between the fundamental and second-order modes propagating on a straight polymer waveguide. Intuitively, the higher the mode order, the larger the fraction of power (evanescent field) propagating outside the waveguide core, hence the higher the sensitivity that can be achieved when interfering against the strongly confined fundamental mode. The device is fabricated using the polymer SU-8 over a SiO2 substrate and shows a free spectral range of 20.2 nm and signal visibility of 5.7 dB, reaching a sensitivity to temperature variations of 0.0586 dB/ ∘ C. The results indicate that the proposed interferometer is a promising candidate for highly sensitive, compact and low-cost photonic transducer for implementation in different types of sensing applications, among these, point-of-care.

scholarly journals Whole Blood Immunoassay Based on Centrifugal Bead Sedimentation

2011 ◽  
Vol 57 (5) ◽  
pp. 753-761 ◽  
Author(s):  
Ulrich Y Schaff ◽  
Greg J Sommer
Keyword(s):  
Whole Blood ◽  
Single Channel ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Microfluidic System ◽  
Blood Samples ◽  
Reactive Protein ◽  
Immunoassay Technique ◽  
Microfluidic Immunoassay

BACKGROUND Centrifugal “lab on a disk” microfluidics is a promising avenue for developing portable, low-cost, automated immunoassays. However, the necessity of incorporating multiple wash steps results in complicated designs that increase the time and sample/reagent volumes needed to run assays and raises the probability of errors. We present proof of principle for a disk-based microfluidic immunoassay technique that processes blood samples without conventional wash steps. METHODS Microfluidic disks were fabricated from layers of patterned, double-sided tape and polymer sheets. Sample was mixed on-disk with assay capture beads and labeling antibodies. Following incubation, the assay beads were physically separated from the blood cells, plasma, and unbound label by centrifugation through a density medium. A signal-laden pellet formed at the periphery of the disk was analyzed to quantify concentration of the target analyte. RESULTS To demonstrate this technique, the inflammation biomarkers C-reactive protein and interleukin-6 were measured from spiked mouse plasma and human whole blood samples. On-disk processing (mixing, labeling, and separation) facilitated direct assays on 1-μL samples with a 15-min sample-to-answer time, &lt;100 pmol/L limit of detection, and 10% CV. We also used a unique single-channel multiplexing technique based on the sedimentation rate of different size or density bead populations. CONCLUSIONS This portable microfluidic system is a promising method for rapid, inexpensive, and automated detection of multiple analytes directly from a drop of blood in a point-of-care setting.

scholarly journals Application of Flexible Display Technology to Low Cost Multiplexed Point-of-Care Medical Diagnostic Testing

2016 ◽  
Vol 2 (3_suppl) ◽  
pp. 14s-14s
Author(s):  
Benjamin A. Katchman ◽  
Joseph T. Smith ◽  
Jennifer Blain Christen ◽  
Karen S. Anderson
Keyword(s):  
Intellectual Property ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Low Cost ◽  
Manufacturing Technology ◽  
Analytical Sensitivity ◽  
State University ◽  
Arizona State University ◽  
New Approach ◽  
Display Technology

Abstract 62 One of the key roadblocks limiting the transition of high-sensitivity and high-specificity point-of-care technologies from the research laboratory to wide spread use is the availability of a low-cost-high-volume manufacturing technology. This work presents a new interdisciplinary approach combining low cost commercial display manufacturing technology with programmable high density protein microarray printing technology to fabricate disposable point-of-care immunosensors with clinical level sensitivity. Our approach is designed to leverage advances in commercial display technology to reduce pre-functionalized biosensor substrate costs to pennies per cm2, as well as to leverage the display industry’s ability to manufacture an immense number of low cost consumer electronic products annually. For this work, we demonstrate that our new approach can offer diagnostic sensitivity at or below 10 pg/mL, which approaches the lower limit of detection of typical clinical laboratory instrumentation. Our new approach is also designed to overcome the limited analytical sensitivity of existing POC devices (>100x improved sensitivity). It also contains new capability for multiplexed biomarker detection (>10 antigens) in a single low cost POC device through an innovative disposable and scalable architecture, based on flat panel display technology. Here, we demonstrate multiplexed detection of antibodies to the HPV16 proteins E2, E6, and E7, which are circulating biomarkers for cervical as well as head and neck cancers. This detection technology has 100 percent correlation to our current laboratory-based measurement instrumentation. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Benjamin A. Katchman Patents, Royalties, Other Intellectual Property: Arizona State University Joseph T. Smith Patents, Royalties, Other Intellectual Property: Arizona State University Jennifer Blain Christen Patents, Royalties, Other Intellectual Property: Arizona State University Karen S. Anderson Stock or Other Ownership: Provista Diagnostics Consulting or Advisory Role: Provista Diagnostics Patents, Royalties, Other Intellectual Property: Arizona State University

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