NUS News

World’s first real-time in-vivo molecular diagnostic system

The complex process of cancer diagnosis can be made simpler, faster and more objective. An NUS biomedical engineering team demonstrated this possibility with a breakthrough In-Vivo Molecular Diagnostic System that they have developed.

This diagnostic system is the only one in the world, so far, clinically proven to be usable in human patients for diagnosing in real time even pre-cancerous tissue in gastrointestinal tract during endoscopic examination. Unlike conventional endoscopic techniques that rely on doctors’ eyeball interpretation of the images, followed by pathologists’ analysis of the biopsy specimen several days later, their diagnostic system utilises computer analysis of biomolecular information and can therefore provide objective diagnosis of cancer almost instantly.

Commenting on the subjectivity of common endoscopic screening techniques, team lead Associate Professor Huang Zhiwei from the Department of Biomedical Engineering explained that the operator’s interpretation of the results is often dependent on and limited by his or her experience and visualisation of the images acquired. Their system, on the other hand, yields results that are independent of the operator.

Time for data collection and assessment is also cut short with the use of a proprietary confocal fibre-optic probe and customised online software control system designed by the NUS team. The confocal fibre-optic probe enables the collection of biomolecular fingerprint of tissues in less than a second; while the online software enables the biomolecular information collected to be extracted and analysed with diagnostic result presented in real time during endoscopic examination.

Based on Raman spectroscopy, a vibrational spectroscopic technique used to collect a unique chemical fingerprint of molecules, the system, however, does not face the typical problem of weak Raman signals, which imply a long wait in data collection. Its specially designed confocal probe not only overcomes this problem but also the technical challenges of high-fibre background noise and lack of depth perception.


To date, the team’s In-Vivo Molecular Diagnostic System has been used in more than 500 patients in Singapore across diverse cancer types such as stomach, oesophagus, colon, rectum, head and neck, and cervix. The researchers have published over 40 peer-reviewed publications—their latest being “Fiberoptic Confocal Raman Spectroscopy for Real Time In-Vivo Diagnosis of Dysplasia in Barret’s Esophagus” (January 2014) in Gastroenterology, the most prominent journal in that field. They have also filed two US and two UK patents for their invention.

For the clinical testing, the NUS Engineering team has been collaborating with researchers from the NUS Yong Loo Lin School of Medicine, led by the School’s Dean Associate Professor Yeoh Khay Guan, Head of Medicine Professor Ho Khek Yu, and Head of Pathology Associate Professor Teh Ming.

Looking back on the team’s research, Assoc Prof Huang said: “It has been a long and tedious journey of more than 10 years. The journey could be longer if not for the excellent cross-disciplinary teamwork at NUS. The contribution of the NUS clinical team is invaluable in demonstrating the clinical benefits of the system.”

On the groundbreaking invention, NUS Medicine Dean Assoc Prof Yeoh said: “This is a first in the world development, pioneered here in Singapore. It has the potential to make enormous clinical impact on how cancer is diagnosed and managed. The immediate point-of-care diagnosis during live endoscopic examinations will provide benefits in time and cost-savings, and will improve our patients’ prognosis as a result of early diagnosis.”

Moving forward, Assoc Prof Huang said they will be conducting clinical trials on a larger scale to further validate the clinical utility of their novel system, especially in gastrointestinal cancers.

Gastrointestinal cancer as a class is very prevalent in Asia, with stomach and colorectal cancer being the most common cancer types. It is also a very treatable cancer class when diagnosed early. Unfortunately, mortality within gastrointestinal cancer is disproportionately high—gastrointestinal cancer is currently the second highest contributor to cancer deaths.

“We look forward to improving the prognosis of patients with gastrointestinal cancer by facilitating early cancer diagnosis with our In-Vivo Molecular Diagnostic System,” he said.

This research is supported by Singapore’s National Research Foundation under its Translational and Clinical Research (TCR) Flagship programme, and is administered by the Ministry of Health’s National Medical Research Council.