Written by Research Scientist, Dr. Venkatesh Srinivasan and Ms. Lin Xuan
The advancement of medical test kits
We have used many medical diagnostic devices at home. Rapid test kit for COVID-19, home diabetes testing unit, pulse oximeter are all examples of medical diagnostic devices.
10 years ago, people had to go to a hospital and have a trained doctor or nurse check their blood pressure or have devices to track their heart beat. Now, we can check our blood pressure at home with the help of an affordable and compact device or track our heart beats/ECGs with smart watches. The majority of such medical devices rely on two methods of detection to reflect the results: 1) the use of electricity and 2) the change in color. Devices that are based on method 1- change in electricity, would logically need electric/electronics setup to function (Example: Digital Glucometers). On the other hand, devices or technologies that are based on method 2- change in color, do not usually need electronics setup (COVID-19 test kits and Pregnancy kits).
Figure 1. COVID-19 rapid test kits.
Gold in our Covid Test Kit?
The Rapid Antigen Test (RAT) or Antigen Rapid Test (ART) - a handy self-administered kit to test for the presence of Covid-19 virus in the human body, relies on the change in colour of the ‘test line’ to determine the result. The rapid test strip technology is capable of generating visible change in colour when the virus is present. How does the change in colour occur? Thanks to nanoscience and light-matter interaction. Would you believe that there is gold in the rapid test kits? Yes. It is true. Gold is present in its nanoparticle form, which causes the red color. Now, you might wonder, isn’t gold supposed to be…gold in color? Why red?
Figure 2. Gold nano-spheres of diameters ranging from 20 to 80 nm
Light-matter interaction happens differently when the material is very small – nano in size. A nano-meter is many times smaller than the thickness of our hair. This means they are so small they cannot be seen with a naked eye. These nanoparticles interact differently with light since they are smaller than the size of a light wave. The spherical gold nanoparticles that are used in ART/RAT kits are red in color. Mind blown? I know! It is pretty cool that we use materials smaller than the wavelength of light (hence the size nano) in the rapid test kits (Nerdy vibes!!). Colour of these nanoparticles can also be adjusted by changing their size, shape or composition. You must be wondering how the color appears in the ART kit only when the virus is present. Gold nanoparticles are the reason for the appearance of red color but the detection of the presence of a particular virus is based on the technique called sandwich ELISA.
Figure 3. Spanners and ELISA analogy.
Finding a spanner in haystack:
Sandwich ELISA is a protein detection technique with high specificity towards any selected protein (sequence of amino acids). The protein of interest here is a select sequence of amino acids on the surface of SARS-CoV-2 (COVID-19 virus) , usually the spike protein. Different ART kits target different sections of the virus. You must be wondering what Sandwich ELISA is? Does it come with Mayo? (Nerdy joke!!)
In Figure 3, we can see different sizes of spanners. Let's say these spanners are different proteins present in the sample but only the spanner 12-13 size is COVID-19 virus protein. Now in order to detect the presence of this amidst all other spanners, we can use size 12 and size 13 nuts. The spanner where both of the nuts would fit is our protein of interest. That is to say, the specifically designed detector proteins “nuts” can fit only with a specific “spanner” in this case the Coronavirus (Covid-19).
Figure 4: T-line showing colour due to presence of sandwich of Detector protein with gold-Virus-Detector protein.
Seeing Red on the T-line
The principle goes like this: As the sample liquid (obtained from the swapped cotton) containing the Covid-19 virus flows across the test kit, it picks up the detector proteins that are tagged with gold nanoparticles. When these (the Covid-19 virus together with the detector proteins) cross the T line, they get attached to the Capture Protein (second nut) that was pre-coated on the T-line. Thus forming a sandwich Detector protein with gold-Virus-Detector protein (Nut 12-Spanner-Nut 13). As the number of ‘sandwiches’ increases at the T line, the red colour of gold nanoparticles becomes visible to the human eye.
The C line is designed to capture the gold nanoparticles so it will always turn red when the kit is used. This is an internal standard to know if the kit has expired or is still functional. In this way, gold’s interaction with light and protein specific sandwich ELISA are instrumental in rapid test kit technology.
I guess you will never look at the simple ART/RAT test the same way again!
Further reading and references:
HiQ Nano Gold
Antibody-doped gold nanoparticles provide a rapid COVID-19 test