IIT Madras led Team Develop Biosensor Platform To Test Pregnant Women For Pre-eclampsia

An Indian Institute of Technology Madras (IIT Madras)-led multi-institute Research Team has developed a new biosensor platform that can test pregnant women for Pre-eclampsia.

The researchers have come together to develop a Point-of-Care (PoC) testing using fiber optics sensor technology as a possible alternative to existing technologies.

Pre-eclampsia (PE) is a life-threatening complication that occurs during pregnancy, affecting a large number of pregnant women and newborns worldwide. Rapid, on-site and affordable screening of this complication at an early stage is necessary to ensure timely treatment and minimize both maternal and neonatal morbidity and mortality rates.

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The usual method to detect pre-eclampsia is time-consuming, requiring huge infrastructure and trained personnel, which makes this test mostly inaccessible to remote areas and resource-limited settings. Therefore, there is an urgent need for an easily accessible, point-of-care testing device with ‘3S’ features (Sensitivity, Specificity and Speed) for the diagnosis of pre-eclampsia.

The Research Team comprised Prof. V.V. Raghavendra Sai and Dr. Ratan Kumar Chaudhary, Department of Applied Mechanics and Biomedical Engineering, IIT Madras, Dr. Narayanan Madaboosi, Department of Biotechnology, IIT Madras, Dr. Jitendra Satija, Centre for Nanobiotechnology, Vellore Institute of Technology, Dr. Balaji Nandagopal and Dr. Ramprasad Srinivasan, Sri Sakthi Amma Institute of Biomedical Research, Sri Narayani Hospital & Research Centre, Vellore.

The findings of this research were published in the reputed journal Biosensors and Bioelectronics (https://doi.org/10.1016/j.bios.2024.116312)

Highlighting the key findings, Prof. V.V. Raghavendra Sai, Biosensors Laboratory, Department of Applied Mechanics and Biomedical Engineering, IIT Madras, said, “Placental growth factor (PlGF) is an angiogenic blood biomarker used for pre-eclampsia diagnosis. Herein, we have established the Plasmonic Fiber Optic Absorbance Biosensor (P-FAB) technology for detecting PlGF at femtomolar level using polymethyl methacrylate (PMMA) based U-bent polymeric optical fiber (POF) sensor probes.”

To detect pre-eclampsia, tests using ‘PlGF’ biomarker are widely in use. This is because this biomarker peaks at 28 to 32 weeks in normal pregnancy but in the case of women with pre-eclampsia, it decreases by 2 to 3 times after 28 weeks of pregnancy.

The POF sensor probes developed by this Research Team could measure PlGF within 30 minutes using the P-FAB strategy. The clinical sample testing confirmed the accuracy, reliability, specificity, and sensitivity of the P-FAB based POF sensor platform, thereby paving the way for cost-effective technology for PlGF detection and its potential for pre-eclampsia diagnosis.

Prof. V.V. Raghavendra Sai added, “The biosensor platform developed by the research team is simple and reliable, paving the way for affordable diagnosis. It can also lead to increasing the test coverage of Placental growth factor (PlGF) biomarker tests, thereby resulting in a potential for a significant impact on the management of pre-eclampsia and towards reduction in the global burden of mortality and morbidity from pre-eclampsia.”

Elaborating on when this technology could reach field implementation, Dr. Narayanan Madaboosi, DBT Ramalingaswami, Re-Entry Fellow, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT Madras, said, “This technology for pre-eclampsia detection has systematically traversed the required validation stages, ranging from analytical through bioanalytical until clinical evaluation, thereby advancing via the associated Technology Readiness Levels (TRL). Further large scale patient sample analysis across diverse clinical settings with this validated biosensor, together with robust prototyping, would enable and smoothen its potential Tech Transfer and subsequent commercialisation in the near- and mid-term future, respectively.”

Pointing to the significance of the technology, Dr. Ratan Kumar Chaudhary, the first author of the research paper, who recently graduated from the Department of Applied Mechanics and Biomedical Engineering, IIT Madras, said, “The P-FAB based POF platform offers transformative technology for detecting pre-eclampsia disease and has potential applications for detecting others communicable and non-communicable diseases.

The P-FAB based POF technology eliminates the use of harsh chemicals and utilizes recyclable POF. This technology is simple, cost-effective, rapid, dip-type that requires a minimum sample volume (30 µL, or a droplet) and is both environmentally and user-friendly. Thus, it holds significant potential and could be used in remote and resource-limited settings for pre-eclampsia diagnosis.”

Highlighting the need for such technologies, Dr. Jitendra Satija, Centre for Nanobiotechnology, Vellore Institute of Technology, said, “The P-FAB strategy is a highly promising point-of-care testing technology that can be employed for the on-site detection of not only pre-eclampsia but also various other diseases such as cancer, tuberculosis, Alzheimer’s, etc. This technology has immense potential for scale-up owing to cost-effective and easy-to-fabricate disposable POF probes that provide results within 30 minutes with minimal use of reagents. We have devoted the last 15 years to this P-FAB research, and we are glad to see its technological evolution and superior sensitivity in terms of detection limit. Although P-FAB technology is still emerging, we are sure that it will be as beneficial as glucose sensors in the near future.”

Speaking about the benefits of the technology developed by this research team, Dr. Ramprasad Srinivasan, Sri Sakthi Amma Institute of Biomedical Research, Sri Narayani Hospital & Research Centre, Vellore, said, “The advantage of this test is that it can detect PLGF at 11-13 weeks of gestation and classify subjects into high-risk and low-risk groups. Low dose aspirin if given early to the high-risk women could decrease the incidence of pre-eclampsia. Hence, this test, let alone being diagnostic, also aids in the treatment and thereby improving maternal and neonatal outcomes.”

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TECHNICAL BACKGROUND

An ultrasensitive plasmonic fiber optic absorbance biosensor (P-FAB) platform was chosen to detect PlGF in pregnant women. This technology conventionally uses glass optical fibers (GOF). But these are expensive, fragile, and involve laborious and precise fabrication steps. Therefore, polymeric optical fibers (POF) were used by this team as an alternative to GOF.

POFs are easy to handle, robust, cost-effective, and flexible. However, the polymethyl methacrylate (PMMA) surface is chemically inert, resulting in poor antibody surface density. Hence, a generation-4 poly(amidoamine) (G4-PAMAM) dendrimer that is hyperbranched, monodispersed, globular, with a three-dimensional structure was used.

This is the first time that PAMAM dendrimer-based strategies have been reported for POF-based biosensing. The POF sensor probe-based P-FAB strategy was found to be highly promising for on-site pre-eclampsia diagnosis that is cost-effective and easy-to-use. This method could contribute towards the reduction of the global burden of mortality and morbidity from pre-eclampsia.