high-performance instrumentation: Mass spectrometry

Challenge

Build a bench top mass spectrometer for protein profiling by non-specialists (biologists).

Key challenges included ensuring quantitative reproducibility, achieving the required dynamic range, and respecting aggressive cost targets.

Solutions

Extensive setup and calibration algorithms to automate the operation of the instrument making it operate at the same level of performance for expert and non-expert users.

Ion optics with very high collection efficiency for quantitative reproducibility. Essentially all ions leaving the surface of the sample are transported to the detector while maintaining the required mass resolution.

Noise shaping, non-linear electronics for optimal dynamic range. Both individual ions and large bunches of ions are clearly resolved above the noise floor of the system. The following spectrum of insulin gives an example of the capabilities of the ion optics together with the electronics. When a relatively high laser intensity is used for desorption, both insulin monomers and insulin multimers are desorbed. The three panels in the figure show a single spectrum at different magnifications on the vertical scale (1x; 100x; 10,000x). The insulin monomer and the multimers from the dimer up to the 36-mer can be clearly seen. The ratio of the intensity of the insulin monomer to the intensity of the 36-mer is 1:85,000.