scholarly journals End-to-end computational approach to the design of RNA biosensors for miRNA biomarkers of cervical cancer

2021 ◽  
Author(s):  
Priyannth Ramasami Sundhar Baabu ◽  
Shivaramakrishna Srinivasan ◽  
Swetha Nagarajan ◽  
Sangeetha Muthamilselvan ◽  
Raghavv Raghavender Suresh ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Reaction Kinetics ◽  
Dynamic Range ◽  
Point Of Care ◽  
Global Public Health ◽  
Efficient Design ◽  
Genetic Circuits ◽  
Kinetics Modelling ◽  
End To End ◽  
Effective Diagnosis

Cervical cancer is a global public health subject as it affects women in the reproductive ages, and accounts for the second largest burden among cancer patients worldwide with an unforgiving 50 percent mortality rate. Poor awareness and access to effective diagnosis have led to this enormous disease burden, calling for point–of–care, minimally invasive diagnosis methods. Here, an end to end quantitative approach for a new kind of diagnosis has been developed, comprising identification of biomarkers, design of the sensor, and simulation of the diagnostic circuit. Using miRNA expression data in the public domain, we identified circulating miRNA biomarkers specific to cervical cancer using multi–tier screening. Synthetic riboregulators called toehold switches specific for the biomarker panel were designed. To predict their dynamic range for use in genetic circuits as biosensors, we built a multivariate linear regression model using a generic grammar of the toehold structure, and thermodynamic features derived from RNA secondary structure and interaction. The model yielded good performance with an adjusted R2 = 0.59. Reaction kinetics modelling was performed to predict the sensitivity of the second–generation toehold switches to the miRNA biomarkers. Simulations showed a linear response between 10nM and 100nM before saturation. Our study demonstrates an end–to–end workflow for the efficient design of genetic ciruits geared towards the effective detection of unique genomic signatures that would be increasingly important in today's world. The approach has the potential to direct experimental efforts and minimise costs. All resources including the machine learning toolkit, reaction kinetics simulation, designed toehold sequences, genetic circuits, data, and sbml files for replicating and utilizing our study are provided open–source (under GNU GPLv3 licence).

scholarly journals Point of Care Diagnostics in the Age of COVID-19

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 9
Author(s):  
Meysam Rezaei ◽  
Sajad Razavi Bazaz ◽  
Sareh Zhand ◽  
Nima Sayyadi ◽  
Dayong Jin ◽  
...  
Keyword(s):  
Point Of Care ◽  
Diagnostic Methods ◽  
Global Public Health ◽  
Current Standard ◽  
Healthcare Facilities ◽  
Major Threat ◽  
Point Of Care Diagnostics ◽  
Recent Outbreak ◽  
Control Virus ◽  
Biosafety Level

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times (>12 h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.

scholarly journals A tandem giant magnetoresistance assay for one-shot quantification of clinically relevant concentrations of N-terminal pro-B-type natriuretic peptide in human blood

2021 ◽  
Author(s):  
Fanda Meng ◽  
Weisong Huo ◽  
Jie Lian ◽  
Lei Zhang ◽  
Xizeng Shi ◽  
...  
Keyword(s):  
Detection Limit ◽  
Giant Magnetoresistance ◽  
Dynamic Range ◽  
Point Of Care ◽  
Sample Volume ◽  
Small Sample ◽  
Broad Dynamic Range ◽  
Gmr Sensors ◽  
Gmr Sensor ◽  
Sample Volume Requirement

AbstractWe report a microfluidic sandwich immunoassay constructed around a dual-giant magnetoresistance (GMR) sensor array to quantify the heart failure biomarker NT-proBNP in human plasma at the clinically relevant concentration levels between 15 pg/mL and 40 ng/mL. The broad dynamic range was achieved by differential coating of two identical GMR sensors operated in tandem, and combining two standard curves. The detection limit was determined as 5 pg/mL. The assay, involving 53 plasma samples from patients with different cardiovascular diseases, was validated against the Roche Cobas e411 analyzer. The salient features of this system are its wide concentration range, low detection limit, small sample volume requirement (50 μL), and the need for a short measurement time of 15 min, making it a prospective candidate for practical use in point of care analysis.

scholarly journals Cervical Cancer – Bench to Bedside

2016 ◽  
Vol 52 (03) ◽  
pp. 144-154
Author(s):  
T. Rajkumar
Keyword(s):  
Cervical Cancer ◽  
Prognostic Markers ◽  
Point Of Care ◽  
Phase 1 ◽  
Dendritic Cell Vaccine ◽  
Gene Signature ◽  
Cell Vaccine ◽  
Indian Women ◽  
Common Cancer ◽  
Radiotherapy Alone

AbstractCervical cancer is the second most common cancer in Indian women and 4th most common cancer in women world-wide. Over nearly two decades, we have carried out epidemiological and molecular studies in cervical cancer, with an intent to identify potential early diagnostic biomarkers, predictive and prognostic markers, develop newer therapies against cervical cancer and identify potential new targets for therapy.Our studies had identified 14 high risk and 10 low risk human papilloma virus (HPV) in our cervical cancer patients for the first time; had identified life style related cofactors in the development of cervical cancer (paan chewing, parity, early age at first sexual intercourse and first childbirth, husband with two or more sexual partners). We have developed a p16 ELISA kit for cervical cancer screening for use at point of care like PHC's; identified a 7 gene signature which help identify patients who can be treated with radiotherapy alone; identified potential prognostic markers for use in the clinic; developed the country's first Dendritic cell vaccine therapy for cervical cancer and completed the phase 1 study; have identified newer potential therapeutic targets for treatment of cervical cancer.

scholarly journals Ultrasensitive and label-free biosensor for the detection of Plasmodium falciparum histidine-rich protein II in saliva

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gita V. Soraya ◽  
Chathurika D. Abeyrathne ◽  
Christelle Buffet ◽  
Duc H. Huynh ◽  
Shah Mukim Uddin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Elimination ◽  
Point Of Care ◽  
Turnaround Time ◽  
Label Free ◽  
Global Public Health ◽  
Interdigitated Electrode ◽  
Sensor Platform ◽  
Electrode Sensor ◽  
Phosphate Buffered Saline

AbstractMalaria elimination is a global public health priority. To fulfil the demands of elimination diagnostics, we have developed an interdigitated electrode sensor platform targeting the Plasmodium falciparum Histidine Rich Protein 2 (PfHRP2) protein in saliva samples. A protocol for frequency-specific PfHRP2 detection in phosphate buffered saline was developed, yielding a sensitivity of 2.5 pg/mL based on change in impedance magnitude of the sensor. This protocol was adapted and optimized for use in saliva with a sensitivity of 25 pg/mL based on change in resistance. Further validation demonstrated detection in saliva spiked with PfHRP2 from clinical isolates in 8 of 11 samples. With a turnaround time of ~2 hours, the label-free platform based on impedance sensors has the potential for miniaturization into a point-of-care diagnostic device for malaria elimination.

scholarly journals In Vitro and In Vivo Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Mamoudou Maiga ◽  
Seong Won Choi ◽  
Viorel Atudorei ◽  
Mariama C. Maiga ◽  
Zachary D. Sharp ◽  
...  
Keyword(s):  
Breath Test ◽  
Point Of Care ◽  
In Vivo Studies ◽  
Co Dehydrogenase ◽  
Preclinical Development ◽  
Breath Tests ◽  
Monitoring Therapy ◽  
Effective Diagnosis

ABSTRACTOne of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of-care manner that does not require invasive sampling. Here we describe the preclinical development of a potentially highly selective TB diagnostic breath test based upon the organism’s CO dehydrogenase activity. After development of the testin vitro, we were able to use the breath test to discriminate between infected and control rabbits, demonstrating that a diagnosis can potentially be made and also that a complex bacterial phenotype can be noninvasively and rapidly studied in the host.IMPORTANCETuberculosis (TB) remains a major infectious cause of disease and death worldwide, and effective diagnosis and then treatment are the tools with which we fight TB. The more quickly and more specific the diagnosis can be made, the better, and this is also true of diagnosis being as close to the patient (point of care) as possible. Here we report our preclinical development of breath tests based upon specific mycobacterial metabolism that could, with development, allow rapid point-of-care diagnosis through measuring the mycobacterial conversion of labeled CO to labeled CO2.

scholarly journals Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics

2015 ◽  
Vol 112 (32) ◽  
pp. E4354-E4363 ◽  
Author(s):  
Fatih Inci ◽  
Chiara Filippini ◽  
Murat Baday ◽  
Mehmet Ozgun Ozen ◽  
Semih Calamak ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Point Of Care ◽  
Medical Diagnostics ◽  
Clinical Samples ◽  
Label Free ◽  
Protein Biomarkers ◽  
Electrical Field ◽  
Color Changes ◽  
Sensing Platform ◽  
Broad Dynamic Range

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients’ homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE2RD), which addresses all these impediments on a single platform. The NE2RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE2RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE2RD’s broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients’ homes.

scholarly journals Agent-based modelling study of antimicrobial-resistant Neisseria gonorrhoeae transmission in men who have sex with men: towards individualised diagnosis and treatment

Sexual Health ◽  
2019 ◽  
Vol 16 (5) ◽  
pp. 514 ◽  
Author(s):  
Adam K. Zienkiewicz ◽  
Nicolás Verschueren van Rees ◽  
Martin Homer ◽  
Jason J. Ong ◽  
Hannah Christensen ◽  
...  
Keyword(s):  
Index Case ◽  
Point Of Care ◽  
New Technology ◽  
Drug Dose ◽  
Transmission Model ◽  
Contact Network ◽  
Global Public Health ◽  
Reference Case ◽  
Dynamic Transmission Model ◽  
Sex With Men

Background Antimicrobial-resistant (AMR) gonorrhoea is a global public health threat. Discriminatory point-of-care tests (POCT) to detect drug sensitivity are under development, enabling individualised resistance-guided therapy. Methods: An individual-based dynamic transmission model of gonorrhoea infection in MSM living in London has been developed, incorporating ciprofloxacin-sensitive and resistant strains. The time-dependent sexual contact network is captured by periodically restructuring active connections to reflect the transience of contacts. Different strategies to improve treatment selection were explored, including discriminatory POCT and selecting partner treatment based on either the index case or partner susceptibility. Outcomes included population prevalence of gonorrhoea and drug dose counts. Results: It is shown that using POCT to detect ciprofloxacin-sensitive infections could result in a large decrease in ceftriaxone doses (by 70% compared with the reference case in the simulations of this study). It also suggests that ceftriaxone use can be reduced with existing technologies, albeit to a lesser degree; either using index case sensitivity profiles to direct treatment of partners, or testing notified partners with strain discriminatory laboratory tests before treatment, reduced ceftriaxone use in our model (by 27% and 47% respectively). Conclusions: POCT to detect ciprofloxacin-sensitive gonorrhoea are likely to dramatically reduce reliance on ceftriaxone, but requires the implementation of new technology. In the meantime, the proportion of unnecessary ceftriaxone treatment by testing partners before treatment could be reduced significantly. Alternatively, index case sensitivity profiles could be used to select effective treatments for partners.

The use of the VerifyNow P2Y12 point-of-care device to monitor platelet function across a range of P2Y12 inhibition levels following prasugrel and clopidogrel administration

2008 ◽  
Vol 99 (02) ◽  
pp. 409-415 ◽  
Author(s):  
Christopher D. Payne ◽  
Ying G. Li ◽  
John T. Brandt ◽  
David S. Small ◽  
Nagy A. Farid ◽  
...  
Keyword(s):  
Platelet Function ◽  
Clinical Utility ◽  
Dynamic Range ◽  
Light Transmission ◽  
Point Of Care ◽  
Antiplatelet Agents ◽  
Limited Range ◽  
Treatment Regimens ◽  
Light Transmission Aggregometry

SummaryVariability in response to antiplatelet agents has prompted the development of point-of-care (POC) technology. In this study, we compared theVerifyNowTM P2Y12 (VN-P2Y12) POC device with light transmission aggregometry (LTA) in subjects switched directly from clopidogrel to prasugrel. Healthy subjects on aspirin were administered a clopidogrel 600 mg loading dose (LD) followed by a 75 mg/d maintenance dose (MD) for 10 days. Subjects were then switched to a prasugrel 60 mg LD and then 10 mg/d MD for 10 days (n=16), or to a prasugrel 10 mg/d MD for 11 days (n=19). Platelet function was measured by LTA andVN-P2Y12 at baseline and after dosing. Clopidogrel 600 mg LD/75 mg MD treatment led to a reduction in P2Y12 reaction units (PRU) from baseline. A switch from clopidogrel MD to prasugrel 60 mg LD/10 mg MD produced an immediate decrease in PRU, while a switch to prasugrel 10 mg MD resulted in a more gradual decline. Consistent with the reduction in PRU, device-reported percent inhibition increased during both clopidogrel and prasugrel regimens. Inhibition of platelet aggregation as measured by LTA showed a very similar pattern to that found with VN-P2Y12 measurement, irrespective of treatment regimens. The dynamic range of VN-P2Y12 appeared to be narrower than that of LTA. With two different thienopyridines, the VN-P2Y12 device, within a somewhat more limited range, reflected the overall magnitude of change in aggregation response determined by LTA. The determination of the clinical utility of such POC devices will require their use in clinical outcome studies.

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