Mass spec is rapidly becoming a key tool at the vanguard of the battle against some of the biggest killers we face.
The application of mass spectrometry to biology began in the 1940s, when heavy stable isotopes were used as tracers to study processes such as CO2 production in animals.
Since then increases in sensitivity and resolution of the instruments, coupled with improvements in the analysis of data, have opened new dimensions in analyses of complex biological systems. And that growing capability has recently been taken to the clinical front line.
Sepsis kills approximately six million people globally per year, from an estimated 31 million cases. Of those who survive, many suffer from life-changing physical and psychological conditions, collectively known as post sepsis syndrome. The key to treatment is swift diagnosis and there has long been a requirement for technology capable of rapidly detecting and identifying infecting bacteria in blood cultures.
Most clinical laboratories use traditional biochemical methods for bacterial ID in sepsis cases, which can only provide more detailed information about the infecting organism once the culture is ready, approximately after 24 hours. Rushana Hussain is a Clinical Scientist in the Microbiology Department at the Royal Bolton Hospital. She focuses on the hospital’s service development and innovation and she wasn’t happy with that timescale at all. So, she conducted a comparative study between the standard laboratory protocol for processing positive blood culture broths collected from patients admitted to the A&E department with suspected sepsis, and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) diagnostic tool from Bruker.
“By incorporating MALDI-TOF MS and an innovative positive blood culture preparation kit into the laboratory workflow, we are able to inform clinicians of the ID of the infectious organism,” She explains. “This gives them more information and allows them to switch from broad-spectrum antibiotics to narrow-spectrum antibiotics, faster, therefore improving patient outcomes and saving costs.”
Hussain and her team used the Bruker MALDI Biotyper and Sepsityper protocol and found, although it takes additional time to perform, there was an overall reduction in turnaround time for a presumptive identification of between 18-23 hours. And when you are waiting to give a diagnosis, that is an impressive saving. And it also has very useful knock-on effects.
“As well as better patient outcomes, the use of technologies such as MALDI-TOF MS reduce the overall costs associated with sepsis, including length of bed stay and cost of broad-spectrum antibiotics,” says Hussain.
And sepsis isn’t the only complex biological analysis that is being taken on by those wielding MS.
Single cell analysis
Fighting cancer continues to be one of the most critical areas for today’s life science researchers around the globe. A foe as strong as cancer requires strong science and a constant push towards developing innovative analysis and testing solutions that can help drive new answers, insights, treatment strategies and drug discoveries.
The application of single-cell inductively coupled mass spectrometry (SC-ICP-MS) to study metal-based chemotherapy resistance cancer, for example, is a very recent development that PerkinElmer has introduced.
Chady Stephan, Senior Manager of Organics at PerkinElmer explains: “With SC-ICP-MS employed in this new way, researchers are now able to get high resolution into the uptake of metal containing drugs like cisplatin at the individual cell and group cell level. This allows them to evaluate how healthy and diseased cells are reacting to treatment and gain a better understanding of how resistance might be reduced or circumvented in diseased cells in the future.”
This is a very interesting step. Traditional ICP-MS only provides information at the group level while Single Cell ICP-MS offers resolution at the cellular level. And once again this MS technique is making the front line of research. Lauren Amable is Staff Scientist at the NIH’s National Institute on Minority Health and Health Disparities and has been using SC-ICP-MS for the study of metal-based chemotherapy resistance in ovarian cancer.
“The problem with studying cisplatin uptake in cells is the methodology,” she says. “Until now, there have not been effective methods to evaluate its uptake. This new technique is based on the ability to measure discrete signals generated from a cell when it enters the plasma and allows for the quantification of cisplatin within individual cells. This shows that cisplatin uptake more closely reflects what occurs within tumor cells. That, in turn, will lead to the development of new strategies to increase cisplatin uptake in cancer cells, translating to better clinical responses.”
And that, of course is always the important factor. When any new techniques are applied to healthcare they must lead to improved clinical outcomes, otherwise it is all a little academic something PerkinElmer know only too well. Stephan again: “Future studies using Single Cell ICP-MS to better understand cisplatin uptake in cancer cells will also likely lead to new therapies not only for the treatment of ovarian cancer, but also for a number of other cancers treated with cisplatin or other metal–based drugs.
“In the big picture, instead of a one-size-fits-all approach to cancer, this new technology will help advance research into personalised treatments tailored to the needs of each patient.”