Hi everyone!
We have found that a mass spectrometry based technology we are working on can do really fast measurements of targeted proteins.
We would like to demonstrate the technology with established biomarkers that have known troubles with conventional assays (e.g. poor selectivity with exiting ELISA approaches etc).
But being the dumb chromatography person that I am, I am not too familiar with which markers that are notoriously in need of better assays.
Therefore: Do you have any suggestions for cool biomarkers to test a proof of concept for a novel MS tech?
I wish you all a great weekend!
It depends on what you mean by fast and sensitive. I know in most fields Elisas can take days depending on the analyze preparation or as quick as 1 hour. If you're both quick
Steven, having worked now for 2+ years in a a hospital - the field is VERY conservative, but also very much cost-driven. MS will always have a very tough time against established techniques such as ELISA on individual existing tests. It also is costly to establish in a lab.
Technical proof of concept has been done already using e.g. PSA as a single biomarker (however valuable it might be), the CPTAC round-robin studies and other. Another challenge though is to prove "commercial" viability - can you do not only same or better, but faster or in a more streamlined way than e.g. ELISA?
MS for targeted assays has one huge potential advantage which is multiplexing, as it carries the promise of high cost efficiency, as well as providing a lot of differential information (think cancer subtyping).
From my point of view the "perfect scenario" for MS is in high-cost environments (disease which is expensive to treat; food or biotherapeutics production) where either multiple testing or combined testing of multiple parameters can be offered.
Hi Christof! Thanks again for such an insightful answer. If think the multiplexing aspect is highly relevant. For example, LC-MS (and GC-MS) is very routine in many hospitals for detemining dozens of small molecule markers in a single method. My experience is also that hospitals are very conservative, and somethime too conservative considering that ELISA methods/tests are not always very reliable og reproducible. E.g. a recent study blew apart virtually all the work done with ELISA on oxytocin. I also think that "high-cost environments" is a good target, towards personal diagnostics in critical cases etc.
Steven, how fast? nanoLC-MS? Responsive gradients? We routinely analyse the peptide hepcidin-25 with cycle time of 2.5 min on a 2.1mm ID column. nanoLC is not an option so far. Downscaling to nanoLC would make a great difference in sensitivity, but we have the issue of dwell volumes and long gradient times.
nanoLC would be nice for say copeptin analysis, at 1-12 pM, and off course all the interleukins at low pg/L (IL-1, etc).
As always, I suspect you have a revolutionary solution, you clever fox :-)
Dear Steven and all - my company has developed several biomarker tests based on mass spec measurement. The argument is a bit more complex than outlined. Are you developing screening or diagnostic tests using MS? They have to different analytical and commercial requirements: Screening tests have to be highly clinically sensitive with generally lower specificity; but it must be simple, fast and above all cheap. These accompany a diagnostic test with must have high specificity but allows lower sensitivity but can be slower more complex and expensive. If you confuse the two then you fail?
we are using MALDI-toF for direct sample analysis in predominantly screening test development.
PS we were surprised that by looking at the clinical pathology and not the existing bio-chemical marker we have developed totally new MS approaches to clinical diagnostics
There are many difficulties with the assay of sclerostin with current kits
In analysis of biomarkers with high demand and need for automation, robotics and stat analysis, mass spectrometry currently can not adequately respond to these needs, although solving ability and specificity are better.
Fernando has a point, and when developing new methods I always stay clear of the "urgently needed" analyses. These cannot be practically implemented at nigh shifts.
Dear Fernando,
With respect but it is because we can use spotting robots , automate and use pattern recognition software that we are using MALDI - Tof mass spectrometry as new faster and cheaper methods in haematology and clinical chemistry. Microbiology is being revolutionised by MALDI-Tof direct identification of bacteria - this is the future.
Steven,
check out something like high mobility group box1 protein. It has quite a few post translational modifications that are being looked at as biomarkers for specific states. For eg acetylation hmgb1 indicates innate immune activation, whilst reduced hmgb1 indicates necrosis. Each of these are only detectable by mass spec, but the methods are published.
http://www.ncbi.nlm.nih.gov/pubmed/22266604
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