Bansi Dhar Malhotra has been playing around with conducting polymers from the 1980’s. Initially he was interested in the physical properties of different conducting polymers. But by the 1990’s he started using them to detect biomolecules. His job at the Delhi Technological University gave him steady inputs of PhD students and a prolific output of papers.
Saurabh Srivastava, drawn by the nanoparticles that Bansi Dhar uses in conjunction with conducting polymers, joined the group only in this decade. The collaboration has been productive. He had also worked with Saurabh Kumar from the IISc Bangalore on paper based biosensors.
Now the trio come together to report making a low-cost paper sensor to detect cancer.
Detecting cancer early improves the chances for successful treatment and survival.
In many types of cancers, the carcinoembryonic antigen, a protein, is found to be elevated in blood and the level can be taken as an indicator. The antigen is normally present at about less than 3 nanograms per millilitre in adult blood. But, in colorectal, breast, lung, pancreatic, stomach, liver and ovarian cancer, the carcinoembryonic antigen blood levels increase.
So if you have an antibody that can ‘sense’ the antigen and, if the electrochemical changes due to this docking of the antigen on the antibody, creates a current which can be detected, we can measure the amount of antigen present in the serum. Nano-structured iron oxide can immobilise the antibody and is a good conductor. But how to get iron oxide nanoparticles with the antibody to stick to paper?
Bansi Dhar Malhotra suggested poly(3,4-ethylene dioxythiophene) polystyrene sulfonate, a conducting polymer to anchor the detectors on paper. Poly(3,4-ethylene dioxythiophene) polystyrene sulfonate – they call it PEDOT:PSS for short – has high conductivity and good thermal stability and can be easily coated as a thin layer on paper. It may even synergise the conductivity of iron oxide and give better results than iron oxide alone.
So they dispersed iron oxide nanoparticles in PEDOT:PSS using sonication and dipped Whatman filter paper in the dispersed solution for about an hour, took it out and dried it in an oven. They dropped a solution of monoclonal antibodies raised against the carcinoembryonic antigen on to the paper electrode and incubated it for some time. Then, they washed off the extra antibodies that were not immobilised by the iron oxide nanoparticles. The paper sensors were stored in the refrigerator till testing.
The scientists treated this paper with various solutions to analyze changes in electrical conductivity. And found that dimethyl sulfoxide increased electrical conductivity by two orders. So they performed further experiments with the paper sensor treated with dimethyl sulfoxide. Bovine serum albumin was also found to improve the sensor’s performance.
The researchers checked the paper sensor’s sensitivity against solutions containing the antigen and found that the sensor gives a linearly increasing output from 4 to 25 nanograms of the antigen per millilitre – just what was needed for testing clinically relevant increases in the antigen. The team also validated the sensor’s efficiency with conventional ELISA in serum samples of cancer patients.
But is the sensor stable under transportation and storage? The team tested and found that, if the paper is stored at four degrees centigrade, 90% activity was retained after 19 days and 82% after 34 days.
They tested the paper sensor after folding and found that it did not change electrical conductivity.
This disposable lightweight paper-based device is low cost to produce, making it a smart point-of-care device which can be used even in rural areas where other cancer detection technologies are not available.
The technology can detect colorectal, breast, lung, pancreatic, stomach, liver and ovarian cancers early, significantly reducing treatment costs.
Analytical Chimica Acta 1056: 135-145 (2019); DOI: 10.1016/j.aca.2018.12.053
Sileesh Mullasseri, CUFOS