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Title: A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep44778· OSTI ID:1399884
 [1];  [1];  [2];  [1];  [1];  [1]
  1. Sandia National Lab. (SNL-CA), Livermore, CA (United States). Dept. of Biotechnology and Bioengineering
  2. Sandia National Lab. (SNL-CA), Livermore, CA (United States). Dept. of Systems Biology

Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. We demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable “LAMP box” supplemented with a consumer class smartphone. The entire assembly can be powered by a 5 V USB source such as a USB power bank or solar panel. The smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device’s utility for widespread clinical deployment. Altogether, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most.

Research Organization:
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)
Grant/Contract Number:
AC04-94AL85000
OSTI ID:
1399884
Report Number(s):
SAND2016-11988J; srep44778
Journal Information:
Scientific Reports, Vol. 7; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 191 works
Citation information provided by
Web of Science

References (81)

The Zika Virus and Pregnancy journal July 2016
Attomolar Zika virus oligonucleotide detection based on loop-mediated isothermal amplification and AC susceptometry journal December 2016
Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study journal April 2016
Detection of Loop-Mediated Isothermal Amplification Reaction by Turbidity Derived from Magnesium Pyrophosphate Formation journal November 2001
The molecular basis of variation in human color vision: Variation in human color vision journal February 2005
Imaging and Sizing of Single DNA Molecules on a Mobile Phone journal November 2014
Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses Using Reverse Transcription Loop-Mediated Isothermal Amplification journal January 2016
Smartphone quantifies Salmonella from paper microfluidics journal January 2013
Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1 journal February 2012
Instrument-Free Point-of-Care Molecular Detection of Zika Virus journal June 2016
High level soluble production of functional ribonuclease inhibitor in Escherichia coli by fusing it to soluble partners journal June 2011
Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens journal May 2014
Loop-mediated isothermal amplification of DNA journal June 2000
Distribution of Dengue Virus Types 1 and 4 in Blood Components from Infected Blood Donors from Puerto Rico journal February 2016
Smartphone-based detection of unlabeled DNA via electrochemical dissolution journal January 2013
Rapid Detection Strategies for the Global Threat of Zika Virus: Current State, New Hypotheses, and Limitations journal October 2016
PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings journal June 2004
Commercialization of microfluidic point-of-care diagnostic devices journal January 2012
Development of a pan-serotype reverse transcription loop-mediated isothermal amplification assay for the detection of dengue virus journal September 2015
Rapid and Real-Time Detection of Chikungunya Virus by Reverse Transcription Loop-Mediated Isothermal Amplification Assay journal November 2006
Mobile Phone Based Clinical Microscopy for Global Health Applications journal July 2009
Quenching of Unincorporated Amplification Signal Reporters in Reverse-Transcription Loop-Mediated Isothermal Amplification Enabling Bright, Single-Step, Closed-Tube, and Multiplexed Detection of RNA Viruses journal March 2016
Dengue Virus Detection Using Whole Blood for Reverse Transcriptase PCR and Virus Isolation journal May 2007
Paper microfluidic extraction and direct smartphone-based identification of pathogenic nucleic acids from field and clinical samples journal January 2014
Age-specific contacts and travel patterns in the spatial spread of 2009 H1N1 influenza pandemic journal April 2013
Loop-Mediated Isothermal Amplification for Direct Detection of Mycobacterium tuberculosis Complex, M. avium, and M. intracellulare in Sputum Samples journal June 2003
Lensfree microscopy on a cellphone journal January 2010
Direct Blood Dry LAMP: A Rapid, Stable, and Easy Diagnostic Tool for Human African Trypanosomiasis journal March 2015
Molecular genetics of inherited variation in human color vision journal April 1986
Loop-mediated isothermal amplification (LAMP): principle, features, and future prospects journal January 2015
Label-free biodetection using a smartphone journal January 2013
A Field-Tailored Reverse Transcription Loop-Mediated Isothermal Assay for High Sensitivity Detection of Plasmodium falciparum Infections journal November 2016
Smartphone based health accessory for colorimetric detection of biomarkers in sweat and saliva journal January 2013
Colorimetric Detection of Dengue by Single Tube Reverse-Transcription-Loop-Mediated Isothermal Amplification journal September 2015
Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease journal May 2016
Point-of-care colorimetric detection with a smartphone journal January 2012
Smartphone Fluorescence Spectroscopy journal August 2014
Zika virus — reigniting the TORCH journal August 2016
Solar thermal polymerase chain reaction for smartphone-assisted molecular diagnostics journal February 2014
Convective PCR Thermocycling with Smartphone-Based Detection: A Versatile Platform for Rapid, Inexpensive, and Robust Mobile Diagnostics book January 2016
Detection of dengue viruses using reverse transcription-loop-mediated isothermal amplification journal August 2013
Lab-on-a-Drone: Toward Pinpoint Deployment of Smartphone-Enabled Nucleic Acid-Based Diagnostics for Mobile Health Care journal April 2016
Quantitative Imaging with a Mobile Phone Microscope journal May 2014
Zika Virus journal June 2017
Development of a loop-mediated isothermal amplification method for rapid detection of caprine arthritis-encephalitis virus proviral DNA journal May 2012
Development and evaluation of real-time loop-mediated isothermal amplification for hepatitis B virus DNA quantification: A new tool for HBV management journal April 2008
Multiplex loop-mediated isothermal amplification (M-LAMP) assay for the detection of influenza A/H1, A/H3 and influenza B can provide a specimen-to-result diagnosis in 40min with single genome copy sensitivity journal September 2013
Neuraminidase inhibitors for treatment of human and avian strain influenza: A comparative modeling study journal January 2011
Rapid detection and typing of influenza A and B by loop-mediated isothermal amplification: Comparison with immunochromatography and virus isolation journal August 2006
Rapid diagnosis of H5N1 avian influenza virus infection by newly developed influenza H5 hemagglutinin gene-specific loop-mediated isothermal amplification method journal May 2007
Development of a reverse transcription loop-mediated isothermal amplification assay for the rapid diagnosis of avian influenza A (H7N9) virus infection journal August 2014
Development of H5-RT-LAMP (loop-mediated isothermal amplification) system for rapid diagnosis of H5 avian influenza virus infection journal November 2006
ZIKV actively induces calcification in the fetal brain journal March 2021
Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse journal January 2017
Multiplex Reverse-Transcription Loop-Mediated Isothermal Amplification Coupled with Cascade Invasive Reaction and Nanoparticle Hybridization for Subtyping of Influenza A Virus journal March 2017
Sample preparation: a challenge in the development of point-of-care nucleic acid-based assays for resource-limited settings journal January 2007
Rapid-Test Sensitivity for Novel Swine-Origin Influenza A (H1N1) Virus in Humans journal August 2009
Rapid Antigen Tests for Diagnosis of Pandemic (Swine) Influenza A/H1N1 journal October 2009
Diagnosis of 2009 Pandemic Influenza A (pH1N1) and Seasonal Influenza Using Rapid Influenza Antigen Tests, San Antonio, Texas, April–June 2009 journal January 2011
Visual detection of human infection with influenza A (H7N9) virus by subtype-specific reverse transcription loop-mediated isothermal amplification with hydroxynaphthol blue dye journal August 2013
Rapid Detection of Tembusu Virus by Reverse-Transcription, Loop-mediated Isothermal Amplification (RT-LAMP): Rapid Detection of Tembusu Virus by RT-LAMP journal September 2011
Detection of Respiratory Viruses by Molecular Methods journal October 2008
Point-of-Care Testing for Infectious Diseases: Past, Present, and Future journal August 2017
Sensitive and Rapid Detection of Herpes Simplex Virus and Varicella-Zoster Virus DNA by Loop-Mediated Isothermal Amplification journal July 2005
Reverse-transcription, loop-mediated isothermal amplification assay for the sensitive and rapid detection of H10 subtype avian influenza viruses journal September 2015
Development of a Reverse Transcription Loop-Mediated Isothermal Amplification Assay for H7N7 Equine Influenza Virus journal January 2012
Serological Response in RT-PCR Confirmed H1N1-2009 Influenza A by Hemagglutination Inhibition and Virus Neutralization Assays: An Observational Study journal August 2010
Visual detection of isothermal nucleic acid amplification using pH-sensitive dyes journal February 2015
Loop-Mediated Isothermal Amplification for Influenza A (H5N1) Virus journal June 2007
Highly Pathogenic Avian Influenza Virus (H5N1) in Domestic Poultry and Relationship with Migratory Birds, South Korea journal March 2008
Tools to Detect Influenza Virus journal January 2013
Zika Virus journal August 2016
Zika virus — reigniting the TORCH text January 2016
Smartphone fluorescence spectroscopy conference March 2015
Outbreak of Kyasanur Forest disease (monkey fever) in Sindhudurg, Maharashtra State, India, 2016 journal June 2016
Correction to “Instrument-Free Point-of-Care Molecular Detection of Zika Virus” journal October 2018
Cholesterol testing on a smartphone journal January 2014
A smartphone platform for the quantification of vitamin D levels journal January 2014
Zika Virus journal March 2016
Rapid Detection and Differentiation of Dengue Virus Serotypes by a Real-Time Reverse Transcription-Loop-Mediated Isothermal Amplification Assay journal June 2005
Antiviral Resistance and Correlates of Virologic Failure in the first Cohort of HIV-Infected Children Gaining Access to Structured Antiretroviral Therapy in Lima, Peru: A Cross-Sectional Analysis journal January 2013

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Innovative and New Approaches to Laboratory Diagnosis of Zika and Dengue: A Meeting Report journal December 2017
Smartphone-based clinical diagnostics: towards democratization of evidence-based health care journal September 2018
Mobile oral heath technologies based on saliva journal February 2018
Beyond Fever and Pain: Diagnostic Methods for Chikungunya Virus journal May 2019
Rapid and simple colorimetric detection of multiple influenza viruses infecting humans using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform journal August 2019
Laboratory Diagnosis and Potential Application of Nucleic Acid Biosensor Approach for Early Detection of Dengue Virus Infections journal June 2018
Detection of Zika virus using reverse-transcription LAMP coupled with reverse dot blot analysis in saliva journal February 2018
A localized surface plasmon resonance-amplified immunofluorescence biosensor for ultrasensitive and rapid detection of nonstructural protein 1 of Zika virus journal January 2019
Advances in Diagnosis, Surveillance, and Monitoring of Zika Virus: An Update journal January 2018
Advances in Directly Amplifying Nucleic Acids from Complex Samples journal September 2019
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Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens journal February 2018
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One-step purification of nucleic acid for gene expression analysis via Immiscible Filtration Assisted by Surface Tension (IFAST) journal January 2011
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An inexpensive smartphone-based device for point-of-care ovulation testing journal January 2019
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2019 Novel Coronavirus Disease (COVID-19): Paving the Road for Rapid Detection and Point-of-Care Diagnostics journal March 2020
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Loop-Mediated Isothermal Amplification (LAMP) for the Diagnosis of Zika Virus: A Review journal December 2019
Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2 text January 2020
Rapid colorimetric detection of Zika virus from serum and urine specimens by reverse transcription loop-mediated isothermal amplification (RT-LAMP) journal September 2017
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Benchmarking Smartphone Fluorescence-Based Microscopy with DNA Origami Nanobeads: Reducing the Gap toward Single-Molecule Sensitivity journal January 2019
Smartphone‐based clinical diagnostics and atrial fibrillation: the need to avoid being out of sight journal May 2019
“The Smartphone’s Guide to the Galaxy”: In Situ Analysis in Space journal October 2018
Synergistically enhanced colorimetric molecular detection using smart cup: a case for instrument-free HPV-associated cancer screening journal January 2019