The research field in which Dr. Anand Natrajan (50) has been working for more than 20 years is highly focused, with only about a dozen or so research groups worldwide working in the area. It deals with the structures and properties of acridinium esters — molecules that emit light in the presence of certain specific chemical triggers. The practical application of this phenomenon called chemiluminescence is in automated immunoassays — that is, in the state-of-the-art test laboratories of large hospitals and central laboratories for clinical diagnostics.

Analytical immunochemistry, commonly referred to as immunoassay, is based on specific interactions between biomolecules, namely the binding of proteins known as antibodies, that are produced by the immune system, to various substances in blood. This binding is highly specific and can be detected and quantified with the help of  ‘labels’ that emit a measurable signal. The first usable immunoassays were developed in the 1970s by the Nobel Prize laureate Rosalyn Yalow, who succeeded in measuring insulin using radioactive isotopes as labels. However, since radioactive materials can only be used under extremely stringent security measures, researchers were on the lookout for more environmentally friendly yet highly sensitive labels.

Luminescent technologies, fluorescence and chemiluminescence, gradually started to replace radioisotopes in clinical immunoassays 

“People started experimenting with chemiluminescent acridinium esters as labels for immunoassays in the 1980s but these labels were quite unstable,” recalls Natrajan. At that time he had just received his doctorate in organic chemistry from Case Western Reserve University in Ohio and was doing postdoctoral research at the University of Virginia. “In 1992, when I went looking for a job, I wanted both to do basic research and to produce results with practical relevance,” explains Natrajan.

Natrajan found a good match in his first job, at the Ciba-Corning Diagnostics company, which was later acqiured by Siemens Healthcare Diagnostics. He, along with his colleagues, started studying chemiluminescent acridinium esters and their modifications for applications in automated immunoassays. Siemens invented the first stable acridinium tracer (Dimethyl Acridinium Ester or DMAE) in the late 1980s.Stable acridinium ester technology proved to be particularly suitable for automation and the first commercial chemiluminescence-based immunoassays were introduced by Siemens Healthcare Diagnostics.

Natrajan has spent almost 20 years studying and manipulating the structures of acridinium esters to produce the best test results in Siemens automated immunoassays. His work encompasses both empirical studies to identify molecules that would be advantageous to use in highly sensitive assays because they emit more light and have less background signal and also basic research to understand the fundamental properties of the light emitting process. As an example of the former, he invented a molecule that emits three times more light and this molecule is used in a highly sensitive assay for the cardiac marker troponin, a biomarker that is indicative of myocardial injury.

More recently he has invented molecules called zwitterionic-acridinium esters that are very water soluble and these new molecules are implemented in assays for Vitamin D and infectious diseases such as hepatitis B. As a chemist who works with chemicals, he is also concerned about the environmental impact of his work. Recently, he identified a chemical process that reduces usage of the toxic chemical propane sultone that is needed for the synthesis of acridinium esters. This new process, which also minimizes potential exposure of personnel to the toxic chemical, is now implemented in the manufacturing of acridinium esters.

Thanks to the results of his work, the technology of immunoassays using chemiluminescent labels has continually improved. Today, automated immunoassays in Siemens Healthcare Diagnostics’ ADVIA Centaur® systems use acridinium ester technology for a wide range of clinical diagnostics in infectious disease testing, endocrinology, fertility, oncology, cardiology etc.   “To this day, I stand in the lab and work with chemicals like a traditional chemist almost every day,” says Natrajan about his work. As a Senior Key Expert, he is particularly happy that he can choose his own approaches to his research. He passes the results of his basic research on to his colleagues in Development, who implement them in the latest generation of ADVIA Centaur® assays. “It’s very satisfying to see how the results of my research lead to new products,” says Natrajan. The results of his creativity include 21 inventions, 47 individual patents granted, and 12 IPR families.

The passionate chemist, who lives with his wife and two golden retrievers in New Hampshire, U.S., is also a car and jazz fan, and spends a large part of his free time reading specialist journals. His favorite ways to relax is to drive his BMW roadster through the New England countryside on a sunny day or playing with his golden retrievers in the park. 

 

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