ASMS 2018 - Thursday Breakfast Seminar 

Vanguard of the Digital Chemical Pathology Revolution – MALDI-ToF mass spectral profiling of a pin-prick of blood for simultaneous detection of thalassemia and haemoglobinopathies. 

--Prof. R.K. Iles (MAP Sciences, Bedford, UK) 

Digital chemical pathology is the ability to transform clinical analysis information from a laboratory test into digital format that can be utilized by Ai to become rapid, cheaper and more accurate diagnostics, driven by pattern recognition software.

Conventional laboratory testing of biological samples (blood, urine, saliva, CSF) is slow, moderately expensive but, worst of all, from a digital stand point, it is mono-dimensional i.e. a single value for a single sample.

Genetic analysis is not mono-dimensional and complete sequence data is rich in terms of disease associations. However:

• Analysis is time-consuming, expensive and complex
• Machine/chemistry has to be interfaced with optical readers to become digital
• Sequence …ATCG… data has to have purpose-built algorithms for recognition and finally association with “probability of disease development” in big data statistics

Mass spectral profiling of biological fluids is multi-dimensional and has many advantages with simultaneous identification of multiple analytes in a single sample run and relative quantification of one analyte against another. Furthermore:

• The sample volume required is micro to nano, preparation is rapid (“dilute and shoot”) and reagent costs are very low
• Data generation is rapid (<1 min) and output is directly digital with no optical interface
• Furthermore, the direct multi-dimensional numeric data is easily handled mathematically

Here we demonstrate MALDI-ToF analysis of a pin-prick of blood for the simultaneous detection of alpha- and beta-thalassemia, sickle cell and numerous haemoglobin mutations, within 30 secs. Furthermore, we demonstrate how an acquired haemoglobinopathy of sulfated Hb was rapidly diagnosed by MALDI-ToF MS when the UK NHS referral poisons unit failed to provide the critical patient diagnosis, thus demonstrating the ability to rapidly detect a non-standard pathology, in a timely manner, by adopting this MALDI-ToF MS technology.