Biosensors on chip: A critical review from an aspect of micro/nanoscales

2019 ◽  
Vol 2 (2) ◽  
pp. 198-219 ◽  
Author(s):  
Geeta Bhatt ◽  
Shantanu Bhattacharya
Keyword(s):  
Optical Sensors ◽  
Microelectromechanical Systems ◽  
Electrochemical Sensors ◽  
Limit Of Detection ◽  
Clinical Diagnostics ◽  
Detection Scheme ◽  
Performance Factors ◽  
On Chip ◽  
Mechanical Sensors ◽  
Sensitivity Specificity

Biosensors are a very well cherished research topic and have found an inseparable status from clinical diagnostics in specific and society at large. As the name suggests, biosensors or biological sensors are devices which detect the presence of biological entities or their constituents and derivatives. The field started decades ago and has matured quite well since its inception. The most important performance factors that are associated with biosensors are sensitivity, specificity, and limit of detection. The remaining efforts of the biosensor research domain focus on miniaturization aspects of the sensors. The growing advancements in this field have evolved the technology of biosensors to cater to full-scale diagnosis on microchips, bedside diagnostics, reduced cost, and increased speed of diagnostics. Biosensors are characterized through many different aspects; for example, one way is to classify them on the basis of the type of bio-recognition step that they would utilize or another way can be based on the type of detection scheme that they may integrate, etc. Depending on the bio-recognition layer’s properties, biosensors can be cell based, nucleic acid probe based, antibody/antigen based, or aptamer based, while depending on the type of detection scheme, biosensors can be viewed as colorimetric sensors, optical sensors, electrochemical sensors, mechanical sensors, etc. There are some other parallel areas of research like microfluidics and microelectromechanical systems where one of the main applications lies in the biosensor domain. This review article discusses the various aspects of biosensors, from their design, realization, to testing, along with various detection strategies. The assembly includes fabrication strategies particularly for microchip technology-based biosensing solutions, microchannels, integration to microfluidics, etc., while categorization deals with various kinds and applications of different biosensors.

scholarly journals Development of a Pharmacogenetic Lab-on-Chip Assay Based on the In-Check Technology to Screen for Genetic Variations Associated to Adverse Drug Reactions to Common Chemotherapeutic Agents

Biosensors ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 202
Author(s):  
Rosario Iemmolo ◽  
Valentina La Cognata ◽  
Giovanna Morello ◽  
Maria Guarnaccia ◽  
Mariamena Arbitrio ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Adverse Drug Reactions ◽  
Limit Of Detection ◽  
Chemotherapeutic Agents ◽  
Clinical Diagnostics ◽  
Individual Risk ◽  
Chip Assay ◽  
Drug Reactions ◽  
Lab On Chip ◽  
On Chip

Background: Antineoplastic agents represent the most common class of drugs causing Adverse Drug Reactions (ADRs). Mutant alleles of genes coding for drug-metabolizing enzymes are the best studied individual risk factors for these ADRs. Although the correlation between genetic polymorphisms and ADRs is well-known, pharmacogenetic tests are limited to centralized laboratories with expensive or dedicated instrumentation used by specialized personnel. Nowadays, DNA chips have overcome the major limitations in terms of sensibility, specificity or small molecular detection, allowing the simultaneous detection of several genetic polymorphisms with time and costs-effective advantages. In this work, we describe the design of a novel silicon-based lab-on-chip assay able to perform low-density and high-resolution multi-assay analysis (amplification and hybridization reactions) on the In-Check platform. Methods: The novel lab-on-chip was used to screen 17 allelic variants of three genes associated with adverse reactions to common chemotherapeutic agents: DPYD (Dihydropyrimidine dehydrogenase), MTHFR (5,10-Methylenetetrahydrofolate reductase) and TPMT (Thiopurine S-methyltransferase). Results: Inter- and intra assay variability were performed to assess the specificity and sensibility of the chip. Linear regression was used to assess the optimal hybridization temperature set at 52 °C (R2 ≈ 0.97). Limit of detection was 50 nM. Conclusions: The high performance in terms of sensibility and specificity of this lab-on-chip supports its further translation to clinical diagnostics, where it may effectively promote precision medicine.

scholarly journals Detector-Free Photothermal Bar-Chart Microfluidic Chips (PT-Chips) for Visual Quantitative Detection of Biomarkers

2021 ◽  
Author(s):  
Wan Zhou ◽  
Guanglei Fu [email protected] ◽  
Xiujun Li
Keyword(s):  
Whole Blood ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Clinical Diagnostics ◽  
Detection Sensitivity ◽  
Quantitative Detection ◽  
Microfluidic Chips ◽  
Analytical Instruments ◽  
Photothermal Effects ◽  
On Chip

<p>The volumetric bar-chart microfluidic chips (V-Chips) driven by chemical reaction-generated gas provide a promising platform for point-of-care (POC) visual biomarker quantitation. However, multiple limitations are encountered in conventional V-Chips, such as costly and complex chip fabrication, complicated assembly, and imprecise controllability of gas production. Herein, we introduced nanomaterial-mediated photothermal effects to V-Chips, and for the first time developed a new type of V-Chip, <u>p</u>hoto<u>t</u>hermal bar-chart microfluidic <u>c</u>hip (PT-Chip), for visual quantitative detection of biochemicals without any bulky and costly analytical instruments. Immunosensing signals were converted to visual readout signals via photothermal effects, the on-chip bar-chart movements, enabling quantitative biomarker detection on a low-cost polymer hybrid PT-Chip with on-chip scale rulers. Four different human serum samples containing prostate-specific antigen (PSA) as a model analyte were detected simultaneously using the PT-Chip, with the limit of detection of 2.1 ng/mL, meeting clinical diagnostic requirements. Although no conventional signal detectors were used, it achieved comparable detection sensitivity to absorbance measurements with a microplate reader. The PT-Chip was further validated by testing human whole blood without the color interference problem, demonstrating good analytical performance of our method even in complex matrixes and thus the potential to fill a gap in current clinical diagnostics that is incapable of testing whole blood. This new PT-Chip driven by nanomaterial-mediated photothermal effects opens a new horizon of microfluidic platforms for instrument-free diagnostics at the point of care.</p>

scholarly journals Detector-Free Photothermal Bar-Chart Microfluidic Chips (PT-Chips) for Visual Quantitative Detection of Biomarkers

2021 ◽  
Author(s):  
Wan Zhou ◽  
Guanglei Fu [email protected] ◽  
Xiujun Li
Keyword(s):  
Whole Blood ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Clinical Diagnostics ◽  
Detection Sensitivity ◽  
Quantitative Detection ◽  
Microfluidic Chips ◽  
Analytical Instruments ◽  
Photothermal Effects ◽  
On Chip

<p>The volumetric bar-chart microfluidic chips (V-Chips) driven by chemical reaction-generated gas provide a promising platform for point-of-care (POC) visual biomarker quantitation. However, multiple limitations are encountered in conventional V-Chips, such as costly and complex chip fabrication, complicated assembly, and imprecise controllability of gas production. Herein, we introduced nanomaterial-mediated photothermal effects to V-Chips, and for the first time developed a new type of V-Chip, <u>p</u>hoto<u>t</u>hermal bar-chart microfluidic <u>c</u>hip (PT-Chip), for visual quantitative detection of biochemicals without any bulky and costly analytical instruments. Immunosensing signals were converted to visual readout signals via photothermal effects, the on-chip bar-chart movements, enabling quantitative biomarker detection on a low-cost polymer hybrid PT-Chip with on-chip scale rulers. Four different human serum samples containing prostate-specific antigen (PSA) as a model analyte were detected simultaneously using the PT-Chip, with the limit of detection of 2.1 ng/mL, meeting clinical diagnostic requirements. Although no conventional signal detectors were used, it achieved comparable detection sensitivity to absorbance measurements with a microplate reader. The PT-Chip was further validated by testing human whole blood without the color interference problem, demonstrating good analytical performance of our method even in complex matrixes and thus the potential to fill a gap in current clinical diagnostics that is incapable of testing whole blood. This new PT-Chip driven by nanomaterial-mediated photothermal effects opens a new horizon of microfluidic platforms for instrument-free diagnostics at the point of care.</p>

scholarly journals Implementation and validation of a pooling strategy for a sustainable screening campaign for the presence of SARS-CoV-2.

2020 ◽  
Author(s):  
Daniela Cesselli ◽  
Michela Bulfoni ◽  
Stefania Marzinotto ◽  
Barbara Marcon ◽  
Sara Cmet ◽  
...  
Keyword(s):  
Mass Screening ◽  
Limit Of Detection ◽  
Healthcare Providers ◽  
Screening Strategy ◽  
Clinical Diagnostics ◽  
Real Population ◽  
Positive Rate ◽  
Reducing Costs ◽  
Asymptomatic Subjects ◽  
Sensitivity Specificity

Mass screening aimed at detecting, in asymptomatic subjects, the presence of SARS-CoV-2 is considered a strategic measure for the control of the present pandemic. It allows virus carriers to be identified and quarantined, thus preventing local spread and protecting vulnerable individuals. Although the screening strategy should be determined by the epidemiological situation, the size of the population that can be screened is indeed limited by the availability of resources. Here we present the implementation of an 8-sample pool strategy that relies on protocols, reagents and equipment currently used in clinical diagnostics. The method permitted to identify, with 100% sensitivity, specificity and accuracy, samples with low viral load, being the limit of detection of 11 viral copies extracted from the equivalent of 133ul of nasopharyngeal sample-pool. When the protocol has been applied, as a proof of principle, in a real population of 3592 consecutive nasopharyngeal swabs collected by healthcare providers in asymptomatic subjects, 20 positive pools were detected and in 100% of cases the positive specimens identified. Considering these performances, the 8-sample pool will allow, in populations with an expected positive rate of less than 1%, reducing costs by at least 80%, being a suitable method for a sustainable mass screening strategy in a population of asymptomatic subjects.

Recent Trends in Development of Nanomaterials Based Green Analytical Methods for Environmental Remediation

2020 ◽  
Vol 16 ◽  
Author(s):  
Sidra Amin ◽  
Amber R. Solangi ◽  
Dilawar Hassan ◽  
Nadir Hussain ◽  
Jamil Ahmed ◽  
...  
Keyword(s):  
Optical Sensors ◽  
Environmental Remediation ◽  
Environmental Chemistry ◽  
Limit Of Detection ◽  
Environmental Pollutants ◽  
Toxic Metal ◽  
Electrochemical Analysis ◽  
Good Choice ◽  
Nano Materials ◽  
Limit Of Quantification

Background: In recent years, the occurrence and fate of environmental pollutants has been recognized as one of the emerging issues in environmental chemistry. A survey documented about a wide variety of these pollutants, which are often detected in our environment and these are major cause of shortened life spans and the global warming. These pollutants include toxic metal, pesticides, fertilizers, drugs and dyes released into soil and major water bodies. The presence of these contaminants causes major disturbance in eco-system’s balance. To tackle these issues many technological improvements are made to detect minute contaminations. The latest issue being answered by the scientists is the use of green nano materials as sensors which are economical, instant and give much better results at low concentrations and can be used for the field measurements resulting in no dangerous by-product that could lead to more environmental contamination. Nano materials are known for their wide band gap, enhanced physical and optical properties with option of tuneablity as per need, by optimizing certain parameters. They are proved to be good choice for analytical/optical sensors with high sensitivity. Objective: This review holds information about multiple methods that use green nanomaterials for the analytical assessment of environmental pollutants. UV-Vis spectrophotometry and electrochemical analysis using green and reproducible nanomaterials are the major focus of this review article. To date, there are number of spectrophotometric and electro chemical methods available that have been used for the detection of environmental pollutants such as toxic metals, pesticides and dyes. Conclusion: The use of nanomaterials can drastically change the detection limits due to having large surface area, strong catalytic properties, and tunable possibility. With the use of nano materials, lower than the marked limit of detection and limit of quantification were seen when compared with previously reported work. The used nano-materials could be washed, dried, and reused, which makes the methods more proficient, cost effective and environmentally friendly.

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 Detection of Active BoNT/C and D by EndoPep-MS Using MALDI Biotyper Instrument and Comparison with the Mouse Test Bioassay

Toxins ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 10
Author(s):  
Ilenia Drigo ◽  
Elena Tonon ◽  
Simone Pascoletti ◽  
Fabrizio Anniballi ◽  
Suzanne R. Kalb ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Animal Health ◽  
Lethal Dose ◽  
Reference Method ◽  
Mouse Bioassay ◽  
Peptide Fragments ◽  
Mass Spectrometers ◽  
Detection And Identification ◽  
Maldi Biotyper ◽  
Sensitivity Specificity

Botulinum neurotoxins (BoNTs) are among the most poisonous known biological substances, and therefore the availability of reliable, easy-to use tools for BoNT detection are important goals for food safety and human and animal health. The reference method for toxin detection and identification is the mouse bioassay (MBA). An EndoPep-MS method for BoNT differentiation has been developed based on mass spectrometry. We have validated and implemented the EndoPep-MS method on a Bruker MALDI Biotyper for the detection of BoNT/C and D serotypes. The method was extensively validated using experimentally and naturally contaminated samples comparing the results with those obtained with the MBA. Overall, the limit of detection (LoD) for both C and D toxins were less than or equal to two mouse lethal dose 50 (mLD50) per 500 µL for all tested matrices with the exception of feces spiked with BoNT/C which showed signals not-related to specific peptide fragments. Diagnostic sensitivity, specificity and positive predictive value were 100% (95% CI: 87.66–100%), 96.08% (95% CI: 86.54–99.52%), and 93.33% (95% CI: 78.25–98.20%), respectively, and accuracy was 97.47% (95% CI: 91.15–99.69%). In conclusion, the tests carried out showed that the EndoPep-MS method, initially developed using more powerful mass spectrometers, can be applied to the Bruker MALDI Biotyper instrument with excellent results including for detection of the proteolytic activity of BoNT/C, BoNT/D, BoNT/CD, and BoNT/DC toxins.

Analytical assessment of ortho clinical diagnostics high-sensitivity cardiac troponin I assay

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Peter A. Kavsak ◽  
Tara Edge ◽  
Chantele Roy ◽  
Paul Malinowski ◽  
Karen Bamford ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
Clinical Performance ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
Clinical Diagnostics ◽  
Ortho Clinical Diagnostics

AbstractObjectivesTo analytically evaluate Ortho Clinical Diagnostics VITROS high-sensitivity cardiac troponin I (hs-cTnI) assay in specific matrices with comparison to other hs-cTn assays.MethodsThe limit of detection (LoD), imprecision, interference and stability testing for both serum and lithium heparin (Li-Hep) plasma for the VITROS hs-cTnI assay was determined. We performed Passing-Bablok regression analyses between sample types for the VITROS hs-cTnI assay and compared them to the Abbott ARCHITECT, Beckman Access and the Siemens ADVIA Centaur hs-cTnI assays. We also performed Receiver-operating characteristic curve analyses with the area under the curve (AUC) determined in an emergency department (ED)-study population (n=131) for myocardial infarction (MI).ResultsThe VITROS hs-cTnI LoD was 0.73 ng/L (serum) and 1.4 ng/L (Li-Hep). Stability up to five freeze-thaws was observed for the Ortho hs-cTnI assay, with the analyte stability at room temperature in serum superior to Li-Hep with gross hemolysis also affecting Li-Hep plasma hs-cTnI results. Comparison of Li-Hep to serum concentrations (n=202), yielded proportionally lower concentrations in plasma with the VITROS hs-cTnI assay (slope=0.85; 95% confidence interval [CI]:0.83–0.88). In serum, the VITROS hs-cTnI concentrations were proportionally lower compared to other hs-cTnI assays, with similar slopes observed between assays in samples frozen <−70 °C for 17 years (ED-study) or in 2020. In the ED-study, the VITROS hs-cTnI assay had an AUC of 0.974 (95%CI:0.929–0.994) for MI, similar to the AUCs of other hs-cTn assays.ConclusionsLack of standardization of hs-cTnI assays across manufacturers is evident. The VITROS hs-cTnI assay yields lower concentrations compared to other hs-cTnI assays. Important differences exist between Li-Hep plasma and serum, with evidence of stability and excellent clinical performance comparable to other hs-cTn assays.

On-Chip Terahertz Near-Field Generation/Detection Scheme

2018 ◽  
Author(s):  
Dmitry S. Bulgarevich ◽  
Yusuke Akamine ◽  
Hideaki Kitahara ◽  
Valynn Katrine P. Mag-Usara ◽  
Hiroyuki Kato ◽  
...  
Keyword(s):  
Near Field ◽  
Detection Scheme ◽  
Field Generation ◽  
On Chip

Electrochemical sensor using carbon nanotube composites for chronic-degenerative diseases diagnosis

MRS Advances ◽  
2020 ◽  
Vol 5 (45) ◽  
pp. 2331-2340
Author(s):  
Antonio Rowland Ramos-Díaz ◽  
Ramon Gómez Aguilar ◽  
Hugo Martínez-Gutiérrez ◽  
Jaime Ortiz-López
Keyword(s):  
Composite Material ◽  
Electrical Response ◽  
Thin Film Transistor ◽  
Carbohydrate Antigen ◽  
Clinical Diagnostics ◽  
Organic Thin Film ◽  
Serum Samples ◽  
Detection Scheme ◽  
Nanotube Composites ◽  
Multi Walled Carbon Nanotubes

AbstractSensitive and selective detection for cancer biomarkers is critical in cancer clinical diagnostics. In this work, we report an electrochemical detection platform for the carbohydrate antigen tumor marker 15-3 (CA15-3). It is based on a composite material of poly [2-methoxy-5- (2-ethylhexyloxy) -1,4-phenylenevinylene] (MEH-PPV) and multi-walled carbon nanotubes (MWCNT), which deposited as active layer of an organic thin-film transistor. This layer was surface functionalized with the Anti-CA15-3 monoclonal antibody. The devices have a favorable electrical output response for VSD source-drain potentials between 0 to 5 volts, and VG as 8 volts. Once the antigen (CA15-3) is recognized by the antibody, the electrical response is diminished. The test has a linear response in the concentration range of 0–30 U mL - 1 of CA 15–3, with a lower detection limit of ~1 U mL - 1 and a stability of 90% with respect to the initial values after storing the device for two weeks. The method was successfully applied to the determination of CA15-3 in serum samples. Possibly, this used composite material has a greater scope and can be applied to another type of detection scheme.

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