The medical profession has a proven and effective antigen test which accurately determines whether a person is infected with the Covid-19 novel coronavirus: the Polymerase Chain Reaction (PCR) test is highly sensitive, so can detect infection even in the early stages of the disease’s progression, when the viral load is low.
There is just one substantial problem with the PCR method: time. The PCR test is a complex, multi-stage process requiring laboratory analysis of swabs taken from the patient’s nose and throat. Normally it takes between 24 and 48 hours for test results to be returned to the patient. And in this time, a mildly infected, asymptomatic person could be mixing with other people and unwittingly transmitting the virus, or subject to preventive quarantine measures, denying them the freedom to travel and socialize normally (see Figure 1).
Management of the Covid-19 pandemic could be improved if a test method could provide a rapid result at home or at the point of care, to enable the immediate quarantining of known infections, even when the patient is asymptomatic, or to determine whether a patient has antibodies indicating that they have previously been infected.
Now a novel application of advanced optical sensing technology by sensor solutions manufacturer ams, based in Premstaetten near Graz, Austria, is making this possible cost-effectively for the first time, and in a format which can be rapidly scaled up to tens of millions of production units.
Fig. 1: A sensitive Covid-19 test allows for detection of asymptomatic patients
Accurate detection of very weak optical signals
The technology underlying the new ams-devised Covid-19 test is chip-scale spectrometry. A laboratory spectrometer is a common type of benchtop scientific instrument costing thousands of dollars. By measuring the spectral power distribution of light reflected from an object, a spectrometer can detect its spectral signature. This is a powerful tool for performing scientific operations such as gas detection and chemical analysis.
Drawing on unique capabilities in on-wafer interferometric optical filter fabrication and silicon photodiode design, ams has developed a family of spectrometers-on-chip which can provide near lab-grade spectral analysis performance in a miniature device which costs a fraction of the price of a benchtop spectrometer.
Now ams has developed a way to apply chip-scale spectral analysis in a test strip kit similar in format to a home pregnancy test kit. The ams technique is being applied now in a test kit for Covid-19, and which can readily be adapted for the testing of other viruses such as influenza, and for use in many other diagnostic applications.
The diagnostic technique common to the ams Covid-19 tester as well as to pregnancy test kits is Lateral Flow Testing (LFT). The principle of LFT is that a test sample – typically blood, saliva or urine, sometimes mixed with a buffer liquid – is applied to a test strip (see Figure 2). The strip consists of an absorbent membrane coated with a conjugate, a reagent sensitive to the antigen, antibody or hormone of interest. Colored nano-particles in the reagent stick to docking points on the strip’s test line, showing as a color of a specific wavelength. The test line appears in minutes after application of the sample to the sample pad.
In a pregnancy test, a sample from a pregnant woman is so heavily loaded with detectable hormones that the colored test line is easy to see with the naked eye.
For Covid-19 testing, however, the user needs to detect the presence of much smaller quantities of reagent activated by antibodies: this will produce a faint test line which is invisible to the naked eye. The new ams design’s deployment of spectral sensing provides for unambiguous and accurate detection of even the smallest amount of antibody: the diagnostic kit includes an optical sensor module consisting of white LEDs and an AS7341L spectral sensor (see Figure 3). The LEDs illuminate the strip’s test line and control line (which checks that the test sample has been properly absorbed by the membrane).
The AS7341L detects reflections in the precise spectral bandwidth which is the optical signature of the Covid-19 antibody. The high sensitivity of the AS7341L makes LFT testing accurate and reliable at the point of care.
Another innovation by ams will enable improved antigen testing (to detect whether a patient is currently infected). Here, the use of fluorescent conjugate illuminated by ultraviolet LEDs will create a much stronger optical signal and thus enable the detection even of early-stage infection in a convenient test strip for use at the point of care.
Fig. 3: A prototype of the Covid-19 LFT test kit developed by ams and Senova
When used in an antibody test kit – testing for whether a person has the antibodies showing that they have had and recovered from infection – the AS7341L can also provide an accurate quantitative read-out to give an indication of the relative amount of antibody in the sample. This provides a strong indication of whether the patient has potentially high or low immunity to the disease.
Provision of a Bluetooth® radio in the test kit enables all results to be communicated via a smartphone, with the patient’s permission, to a cloud service where it can be used by local, national or international health agencies for pandemic monitoring.
Platform for instant diagnostics at the point of care
ams and its partners in industry have developed a prototype LFT test kit for Covid-19 in a very short period – as of April 2020, the first kit developed with German manufacturer Senova is being readied for mass production starting in September 2020.
But because the design is based on a spectral sensor, it provides a platform for future diagnostic test kits for viruses or hormones which use different colorants in the conjugates. All such diagnostic kits can be based on the same AS7341L-based hardware, helping to reduce the cost and increase the mass production capability of a range of diagnostic test kits.
While ams is pleased to be able to make a contribution to the global response to the Covid-19 pandemic, the potential to provide a long-lasting solution for rapid diagnosis of many infections at home or at the point of care is equally satisfying.
Filip Frederix has worked for more than 20 years in the field of nanotechnology for healthcare products and is author of several publications and patents. Filip joined ams in October 2017 to spearhead the ams marketing efforts for Smart Medical Devices within the Imagine New Sensor Division. Recently, he became the director of the Health Segment within the business line Accessories and Wearable Solutions. With a proven track-record in starting new business opportunities, Filip´s background includes working as an independent consultant supporting life sciences startups with capital raising and their business strategy. The largest part of his career was spent at NXP as a program director and new business development manager for healthcare products. In 2004 Filip won the prestigious DSM award, where he continued to work on emerging business projects at DSM in the Netherlands. While working as a post-doctoral researcher at IMEC, he earned his PhD degree in Chemistry from the University of Leuven in 2004. He serves as part-time professor at the University of Hasselt (since 2013).
Frederix will appear on a panel as part of Sensors Innovation Week at 11:45 a.m. ET on Thursday July 16. The full agenda and registration for the free event are online.