Mass spectrometry: How this important research tool is used in a clinical setting

by Anna Lodge

Mass spectrometry may be a technique you only vaguely remember from your chemistry A-levels. Although you may not have thought much about it since then, mass spectrometry is now one of biomedicine’s most powerful imaging methods. Mass spectrometry imaging (MSI) has been used by scientists in fields as diverse as oncology, neurology, cardiology, and rheumatology since the 1960s, yet it’s not widely understood outside those circles.

Figure 1: Ejection of particles from a sample surface after being blasted by primary ions.

How does mass spectrometry work?

MSI is used to visualise the spatial distribution of a substance in a sample. A mass spectrometer comprises 3 main parts: the ion source, the mass analyser, and the ion detector. All of these are essential in measuring the mass-to-charge ratio (m/z) of an ion. By selecting a peak corresponding to the m/z of an ion in a compound of interest, the compound’s distribution in a sample can be mapped, creating an image.

I conducted my master’s research on time-of-flight secondary ion mass spectrometry (ToF-SIMS). To simplify, “ToF” refers to the type of mass analyser, and “SIMS” refers to the ion source. SIMS works by blasting high-energy primary ions onto the sample surface, which causes particle ejections. A ToF mass analyser determines the m/z of an ejected secondary ion by measuring its time of flight from the sample surface to the detector. The sample being imaged can be a thin film, such as a mixture of amino acids, or a solid surface, such as cells or a section of an organ.

Figure 2: ToF-SIMS instrument (Ionoptika, UK).

How is MSI useful?

ToF-SIMS’s high sensitivity and spatial resolution with no need for labelling make it a valuable tool for biomedical imaging. Its application ranges from histological studies of tissue to measuring drug uptake in cells.

ToF-SIMS has shown considerable potential for studying 3D spatial biomolecular distribution in biological samples. For example, it’s been used to measure the depth of distribution of two antibiotics produced by a microbial system (Streptomyces coelicolor). Using ToF-SIMS, researchers were able to show that one antibiotic is located at the microbe’s surface, and the other is predominately located subsurface. This technique has enabled a better understanding of drug resistance and bacterial perseverance.

Another area where ToF-SIMS has value is in drug development. Because of the high attrition rate of trial compounds, many medicines are costly. To minimise costs, drug failures must be identified early. Being able to determine the concentration of a drug at its target site would enable more accurate predictions of its pharmacological effect.

My research using mass spectrometry

My master’s research focused on improving quantitative analysis using ToF-SIMS to facilitate biomedical research. To this end, I imaged sections of mouse kidney tissue doped with paracetamol. The objective was to test the sensitivity of SIMS to paracetamol on a tissue matrix.

Figure 3: Secondary ion image of paracetamol deposited onto kidney tissue.

In Figure 3, we can see 2 signals: blue, which corresponds to choline (m/z 104.13), and pink, which corresponds to paracetamol (m/z 152.07). Choline, a metabolite, is vital in maintaining normal membrane function and structure. It’s also a precursor of betaine, which is produced by the kidney to maintain water balance. In this image, the blue signal represents the structure of the kidney tissue.

Continuing advancements in MSI are now facilitating its use in clinically relevant studies. Perhaps we’ll start to hear more about this exciting technique?