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 Developments in Transduction, Connectivity and AI/Machine Learning for Point-of-Care Testing

Sensors ◽  
2019 ◽  
Vol 19 (8) ◽  
pp. 1917 ◽  
Author(s):  
Shane O’Sullivan ◽  
Zulfiqur Ali ◽  
Xiaoyi Jiang ◽  
Reza Abdolvand ◽  
M Selim Ünlü ◽  
...  
Keyword(s):  
Machine Learning ◽  
Data Analytics ◽  
Point Of Care ◽  
Developed Countries ◽  
Clinical Diagnostics ◽  
Least Developed Countries ◽  
Point Of Care Testing ◽  
Middle Income ◽  
Lab On Chip ◽  
On Chip

We review some emerging trends in transduction, connectivity and data analytics for Point-of-Care Testing (POCT) of infectious and non-communicable diseases. The patient need for POCT is described along with developments in portable diagnostics, specifically in respect of Lab-on-chip and microfluidic systems. We describe some novel electrochemical and photonic systems and the use of mobile phones in terms of hardware components and device connectivity for POCT. Developments in data analytics that are applicable for POCT are described with an overview of data structures and recent AI/Machine learning trends. The most important methodologies of machine learning, including deep learning methods, are summarised. The potential value of trends within POCT systems for clinical diagnostics within Lower Middle Income Countries (LMICs) and the Least Developed Countries (LDCs) are highlighted.

scholarly journals Pharmacodynamic genetic polymorphisms affect adverse drug reactions of haloperidol in patients with alcohol-use disorder

2017 ◽  
Vol Volume 10 ◽  
pp. 209-215 ◽  
Author(s):  
Michael Sergeevich Zastrozhin ◽  
Vadim Brodyansky ◽  
Valentin Skryabin ◽  
Elena Grishina ◽  
Dmitry Ivashchenko ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Genetic Polymorphisms ◽  
Adverse Drug Reactions ◽  
Alcohol Use Disorder ◽  
Drug Reactions

scholarly journals A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes

2020 ◽  
Author(s):  
Jesus Rodriguez-Manzano ◽  
Kenny Malpartida-Cardenas ◽  
Nicolas Moser ◽  
Ivana Pennisi ◽  
Matthew Cavuto ◽  
...  
Keyword(s):  
Real Time ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Lamp Assay ◽  
High Rate ◽  
Epidemiological Surveillance ◽  
Clinical Samples ◽  
Lab On Chip ◽  
Point Of Care System ◽  
On Chip

AbstractThe COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (< 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 ± 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 ± 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.One Sentence SummaryWe demonstrate isothermal detection of SARS-CoV-2 in under 20 minutes from extracted RNA samples with a handheld Lab-on-Chip platform.

scholarly journals Design and Analysis of Silicon Nanowire FET for the Detection of Cardiac Troponin I Biomarker

2021 ◽  
Author(s):  
Shaik Ahmadsaidulu ◽  
B. Vamsi Krsihna ◽  
B V V Satyanarayana ◽  
Durga Prakash Matta
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Limit Of Detection ◽  
Human Life ◽  
Silicon Nanowire ◽  
Drain Current ◽  
Cardiac Troponin I ◽  
Lab On Chip ◽  
Immobilized Antibodies ◽  
On Chip

Abstract Cardiac arrests are one of the major health problems in present days. Cardiac Troponin-I (cTnI) is one of the important enzymes that causes cardiac arrest. Early diagnosis and proper medication of this saves human life. One of the prominent devices to diagnose troponin I is FET based bio-sensor. Normally, for these sensors’ higher sensitivities will be obtained as these biosensors structure consists of nanowire FETs. Proper selection of materials, dimensions, and doping concentrations of nanowire FET imply the perfection of a nanowire FET-based biosensor. In this work, Silicon Nanowire (SiNW) FET sensor is designed and simulated using COMSOL Multiphysics. Through this design, Identified the presence of different concentrations of cTnI present in human blood. The presence of different enzymes like cTnT, cTnI etc., bring changes in characteristics of SiNW FET sensor. With these changes in characteristics, we can identify the presence of these enzymes of a lower concentration also. The lower concentrations of these biomarkers will bring notable changes in the drain current. The characteristics were analysed with the SiNW FET which is equipped with immobilized antibodies on it. The considerable changes observed in these characteristics of FET sensor identifies the presence of cTnI biomarker and are attached to the monoclonal Antibodies (mAb). Our observations shown that the properties of designed SiNW FET changes with presence of these bio marker materials and a limit of detection is obtained the order of 2pg/mL. with further the design bio sensor with SiNW FET can be used for microfluidic and Lab-on-Chip applications also.

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>

Effects of CYP2C19*17 Genetic Polymorphisms on the Steady-State Concentration of Diazepam in Patients With Alcohol Withdrawal Syndrome

2020 ◽  
pp. 001857872093175
Author(s):  
Valentin Yurievich Skryabin ◽  
Mikhail Zastrozhin ◽  
Marco Torrado ◽  
Elena Grishina ◽  
Kristina Ryzhikova ◽  
...  
Keyword(s):  
Steady State ◽  
Genetic Polymorphisms ◽  
Adverse Drug Reactions ◽  
Alcohol Withdrawal ◽  
Withdrawal Syndrome ◽  
Alcohol Withdrawal Syndrome ◽  
Efficacy And Safety ◽  
Drug Reactions ◽  
Steady State Concentration ◽  
State Concentration

Background: Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. Aim: The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. Materials and Methods: The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, anxiety, fear, and emotional tension, patients received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 − 806C>T genotypes: (*1/*1) −12.0 [−15.0; −8.0], (*1/*17+*17/*17) −7.0 [−14.0; −5.0], P < .001, as well as the results of TDM: ( CC) 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/*17) 89.12 [53.26; 178.07] ng/mL, P < .001. Conclusion: Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes.

An efficient technique for the reduction of wavelength noise in resonance-based integrated photonic sensors

The Analyst ◽  
2014 ◽  
Vol 139 (22) ◽  
pp. 5901-5910 ◽  
Author(s):  
Farshid Ghasemi ◽  
Maysamreza Chamanzar ◽  
Ali A. Eftekhar ◽  
Ali Adibi
Keyword(s):  
Systematic Study ◽  
Limit Of Detection ◽  
Efficient Technique ◽  
Lab On Chip ◽  
Silicon Photonic ◽  
Photonic Sensors ◽  
On Chip

A systematic study of the limit of detection (LOD) in resonance-based silicon photonic lab-on-chip sensors is presented.

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