Engineering rapid and sensitive electronic diagnostics for dengue and Zika viruses

Abstract

Background: Dengue and Zika are members of the flavivirus family of arthropod-borne viruses. Given shared ecology and mosquito vectors, Zika is emerging in areas with endemic dengue virus transmission. Immunity studies indicate that dengue shows substantial cross-reaction to Zika and increases the chances of Zika infection, posing a rising global public health threat. Current diagnostic technologies take place in a centralised laboratory and are usually expensive, time-consuming and requiring specialist equipment and personnel. Continued emergence of dengue and Zika viruses, coupled with a lack of effective global surveillance, raises the need for a quantitative, rapid and sample-to-answer diagnostic device. We therefore aim to develop an integrated and innovative diagnostic device, deployable in a wide range of healthcare settings for populations suffering from epidemic diseases.Methods & Materials: Our approach relies on ultrasensitive and precise nucleic acid amplification coupled with pH-sensing complementary metal-oxide semiconductor (CMOS) technology integrated in a lab-on-chip platform. The pH-sensing microchip integrates more than 4000 sensors and employs label-free loopmediated isothermal amplification (LAMP). The hydrogen ions released during the amplification reaction are measured in realtime and are proportional to the amount of double-stranded DNA produced. Specific LAMP primers for dengue and Zika viruses were investigated based on their nucleotide sequence alignment, which includes more than 500 recent outbreak strains of each virus.Results: We report the molecular detection and quantification of 4 serotypes of dengue and Zika viruses by our lab-on-chip platform. Experiments were conducted with a real-time PCR instrument and the platform simultaneously. Time to positive was achieved from 10 to 40 mins from 10 5 to 10 1 copies per reaction, confirming both rapid detection and sensitivity. Conclusion:We have developed a first of its kind portable diagnostic device able to detect the 4 dengue serotypes and Zika in a quantitative and rapid way using our lab-on-chip platform. The information collected from the device has the potential to improve diagnosis and treatment for infectious diseases and contribute to real-time surveillance and epidemiology. Clinical tests for this new technology will be conducted in dengue and Zika epidemic countries, including Thailand and Taiwan.

Discrimination of bacterial and viral infection using host-RNA signatures integrated in a lab-on-chip platform

“…This development is performed with a conventional qPCR instrument using isothermal amplification chemistries, which is then translated on an ion-sensitive field-e ect transistor (ISFET) based LoC platform yielding a method referred to as electronic reverse transcriptase quantitative loop mediated isothermal amplification (RT-qLAMP), or RT-eLAMP [5]. Our LoC platform based on metal-oxide-semiconductor (CMOS) technology is indeed in a full development stage and we have already reported the successful detection of different infectious diseases such as Plasmodium falciparum cause of Malaria [7], Dengue [8], Zika [9] and most recently SARS-CoV-2 [10].…”

Discrimination of bacterial and viral infection using host-RNA signatures integrated in a lab-on-a-chip technology

“…This development is performed with a conventional qPCR instrument using isothermal amplification chemistries, which is then translated on an ion-sensitive field-effect transistor (ISFET) based LoC platform yielding a method referred to as electronic reverse transcriptase quantitative loop mediated isothermal amplification (RT-qLAMP), or RT-eLAMP [5]. Our LoC platform based on metal-oxide-semiconductor (CMOS) technology is indeed in a full development stage and we have already reported the successful detection of different infectious diseases such as Plasmodium falciparum cause of Malaria [7], Dengue [8], Zika [9] and most recently SARS-CoV-2 [10].…”

Rapid Detection of Azole-Resistant Aspergillus fumigatus in Clinical and Environmental Isolates by Use of a Lab-on-a-Chip Diagnostic System

“…This platform combines ion-sensitive field-effect transistors (ISFETs), fabricated in unmodified complementary metal-oxide semiconductor (CMOS) technology, with loop-mediated isothermal amplification (LAMP) and an AndroidOS application for data acquisition, visualization and cloud connectivity. Electrochemical sensing using ISFETs removes the need for bulky and complex optical equipment, while LAMP eliminates the requirement for thermocycling -reducing the hardware complexity, power consumption and size of the diagnostic platform (20)(21)(22)(23)(24).…”