MISER - 650K Injections in 6 Months
MISER: Multiple Injection, Single Experiment Run
High-throughput LC-MS/MS solutions are needed to quickly run assays on libraries of hundreds of thousands, or millions, or drug candidates. Pushing our Waters Acquity HPLC stack to its limit yields a cycle time of 40 seconds, but with some experimental firmware and hardware modifications we can push this to 18 seconds.
While not as fast as, for example, the Agilent Rapidfire with <8s cycle times, this could be a cheap, user-installed modification to existing Acquity instruments that would enable high-throughput analyses.
I worked through various hardware changes and firmware modifications in order to gradually push down our cycle times while retaining adequate analytical performance. With a custom packed C18 column, we had stable elution peaks at 80,000 injections, even with our ~3K PSI pulses of pressure per injection. And with custom wash sequences, we can reduce our carryover to 1-3%.
Since no existing Waters software could handle our volume and form of data, I wrote a raw file reader and analysis tool in C++/Armadillo (Grover.exe) that could extract MRM traces, pick peaks, and calculate some useful summary statistics.
I then prototyped an R/Shiny app that could quickly visualize the output from my C++ parser.
A picture of our setup:
I broke a lot of parts testing this prototype system:
← Back to home