The Acceleration of Innovative Clinical Mass Spectrometry

Mass Spectrometry (MS) has been used in clinical research since the 1970s, and has been used in routine clinical labs for some years now. In the late 1990s, tandem MS was being utilized for neonatal metabolic screening, and the same technology has also been used for drug monitoring since the mid 1990s.

However, the perception of MS is sometimes outdated, that the machines are archaic and very difficult to use analytical giants, hidden in laboratory basements. The reality of modern MS couldn’t be more different. These days, MS is state-of-the-art and, while they are not yet completely ‘turnkey’ analyzers, the technology is certainly much more user-friendly than it once was. MS is also a cost-effective option for the clinical lab, as once the technology has been implemented, running costs can be modest.

Custom-Built Facility

If proof of the era of the modern clinical mass spectrometer is required, one needs look no further than Cheshire, UK. In September 2014, Waters Corporation opened a brand new, custom-built MS facility in Wilmslow. The facility has been designed and equipped to accelerate innovation in the field of MS. It is at this facility that Mike Morris, Waters Corporation’s Senior Director of Mass Spectrometry Research and his team are developing revolutionary new MS technology that can be applied to potential clinical diagnostic applications.

In July 2014, Waters acquired Rapid Evaporative Ionization Mass Spectrometry (REIMS) technology from MediMass Ltd. REIMS is an ionization technique for the direct analysis of samples by mass spectrometry. This ambient sampling technique has shown promise in a number of different applications such as; food safety, microbiology and clinical diagnostics.

REIMS technology has been used by researchers to characterize ex vivo tissue samples, creating a database of nearly 3000 tissue-specific mass profiles (1). In order to adapt the technology for use in vivo, the same researchers created an electrosurgical knife known as the Intelligent Knife or iKnife. The iKnife heats tissue as it cuts, creating a smoke or vapor from the tissue that is ionized using REIMS technology. This smoke is then analyzed using a mass spectrometer to give chemical composition information on the cells that the iKnife is cutting.

Real-Time Diagnostics

The iKnife is currently in development between Water and Imperial College London, where the research team published a paper last year in the journal Science Translational Medicine (1). The article gave results of a preliminary study aimed at validating the techniques possible application for in vivo diagnostic during surgery – by analyzing fresh tissue samples ex vivo. The results of the study showed that the REIMS approach was able to differentiate in 100% of cases between distinct histological and histopathological tissue types. The research team is now conducting larger studies to assess whether the iKnife can be used to provide diagnostic information in real-time during surgical procedures.

The iKnife shows huge promise for surgical teams; analyzing in vivo tissue reduces the chance that diseased tissue might not be removed during surgery; and could potentially eliminate the requirement for samples to be excised mid-surgery and sent to the lab for analysis while the patient remains under anaesthesia. Other clinical diagnostic applications for REIMS technology could be envisioned in the histopathology laboratory, where it is thought that the technology could be used to help chemically characterize particular tissue types in histology tissue sections. Furthermore, once an extensive database of tissue samples has been generated, it is theoretically possible that REIMS technology could be used to not just characterize tissue types, but also to diagnose different disease states.

Mass spectrometry as a technique has specific advantages in clinical chemistry and toxicology over the more traditional immunoassays widely employed; in particular, mass spectrometry offers improved analytical sensitivity and specificity. Now that Waters Corporation is developing REIMS technology, the advantages of mass spectrometry for use in clinical diagnostics has expanded considerably, to include exciting applications in both microbiology and histopathology. This is an area to watch with interest over the next few years.


References:
1. J. Balog, L. Sasi-Szabó, J. Kinross, M. R. Lewis, L. J. Muirhead, K. Veselkov, R. Mirnezami, B. Dezső, L. Damjanovich, A. Darzi, J. K. Nicholson, Z. Takáts, Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry. Sci. Transl. Med. 5, 194ra93 (2013).

Image: In September 2014, Waters Corporation opened a brand new, custom-built MS facility in Wilmslow.