A Single Cell time-of-flight Mass Spectrometer (SCMS) that is enabled by the use of a nanoparticle based MALDI matrix will be fabricated and tested. Unlike traditional surface-receptor-based cell phenotyping and identification techniques, the SCMS system will be able to differentiate between cell types that are indistinguishable using traditional antibody based methods. The label-free method will provide molecular information on individual cells that will lead to a new understanding of the molecular variance in heterogeneous cell mixtures. Another mode of operation allows for the use of either fluorescent, nanoparticle or elemental tags (e.g. lanthanides), to provide a highly multi-plexed labeling method using the single cell mass spectrometer as the detector. The SCMS will also have the capability to be coupled to a cytometer which can be used to isolate cell populations of interest prior to mass spectrometry analysis. Here, cell populations labeled with a fluorescent antibody can be further analyzed to measure the variance and identify sub-populations within the tagged cells.
