The test involves loading extracted DNA and RNA from a nasal or throat swab onto a single-use disposable cartridge. The cartridge is loaded onto the LoC device, which contains an array of ion-sensitive field-effect transistor (ISFET) sensors integrated on a complementary metal-oxide semiconductor (CMOS). The single-use cartridge with the CMOS is plugged into the main device. The main device contains a microcontroller, similar to a small computer, that acquires and processes the data. The microcontroller also transfers the data retrieved from the test via Bluetooth to a smartphone app and secure cloud server.
Each ISFET sensor measures ion concentrations in solution. When the ion concentration changes, the current in each sensor or pixel varies as well. An ISFET is similar to a metal-oxide-semiconductor field-effect transistor (MOSFET). The difference is that in an ISFET, the gate connection is tied to a reference electrode in contact with the solution. Also, the gate oxide is replaced with an ion-sensitive insulating layer.
CMOS is a technology that enables microchips to acquire, store and transmit large amounts of information. The CMOS for this particular test contains over 4,000 electrochemical sensors.
The sensors allow ion imaging of the reaction on the surface of the chip. If the sample contains the RNA of the active virus, the device performs an amplification reaction and protons are released in the solution. When the concentration of hydrogen ions increases, the pH drops. Thus, the solution becomes more acidic.
“One of the benefits of using smartphone technology is that everyone has such a device in their pocket,” said Dr. Nicolas Moser, research associate at the Department of Electrical and Electronic Engineering at Imperial College London and a member of the team. “With a custom app, a smartphone can be used to implement advanced algorithms to process the data.”
Moser added that a handheld device is cheaper than using a computer. With only a single battery, a doctor could administer multiple tests at once.
“Each lab-on-chip (LoC) cartridge contains a control sample to ensure that the result from the swab is accurate,” Moser said. “During our clinical validation, we will also measure the results of the validation with an analysis from a quantitative polymerase chain reaction machine (qPCR machine), which amplifies and detects DNA. In addition, we will use other gold-standard methods of virus detection to validate the performance of our LoC test.”
The team is currently working to ensure the chip’s seal is reliable. A tight seal will prevent contamination of the sample.
“We’ve switched to 3D printing from our previous manufacturing technology and adopted a new design,” said Matthew Cavuto, a graduate student and research assistant on the team. “Luckily our 3D printer, the Figure 4 from 3D Systems, can print our microfluidic chips very quickly. Between March and June of 2020, we went through probably 30 versions of the design. That’s been our primary troubleshooting technique, iterating and experimentally testing as rapidly as possible.”
The current test was developed from technology the team started researching two years ago. The technology was originally designed to address outbreaks of the Zika virus.
“The LoC has the advantage of offering versatility to a wide range of infectious diseases,” Moser said. “It was designed to detect dengue and trialed in Taiwan and, later, malaria and trialed in Ghana. In March 2020, we adapted the test to detect the novel coronavirus.”
Moser and Cavuto said Imperial College London has allowed the team access to the lab through the pandemic. Work conditions have been similar to those under normal circumstances, except for new requirements to socially distance and wear masks and gloves at all times.
“At times, we had difficulty obtaining printed circuit boards and electronics from China,” Cavuto said. “Their manufacturing facilities were closed.”
The team has been able to continue research because the project is deemed essential to the current COVID-19 pandemic.
Moser said that during and after the clinical trials, the team will develop training to teach healthcare providers how to administer tests. The team is also determining how to synchronize data from tests and store them on a secure cloud server.
“We further hope to take the anonymous information retrieved from the tests and synchronize it onto a global map that we’ve developed,” Moser said. “That will track the evolution of data in a completely automated way. It will give countries reliable information to make decisions regarding public health.”
The current members of the research group are Georgiou, Dr. Jesus Rodriguez Manzano, Moser, Cavuto, Ivana Pennisi, Kenny Malpartida Cardenas, Ahmad Moniri and Luca Miglietta. To learn more about the Imperial College London team’s research, read their published papers on rapid detection and mobile detection system.