Promise of multiphoton detection in discovery and diagnostic proteomics.

Proteomics has lacked adequate methods for handling the complexity (hundreds of thousands of different proteins) and range of protein concentrations (> or =10(6)) of eukaryotic proteomes. New multiphoton-detection methods for ultrasensitive detection of proteins produce 10,000-fold gains in sensitivity and allow highly quantitative, linear detection of 50 zmol (30,000 molecules) to 500 fmol of proteins in complex samples. The potential of multiphoton detection in top-down proteomics analyses is illustrated with applications in monitoring proteomes in very small numbers of cells, in identifying and monitoring complex functional isoforms of cancer-related proteins, and in super-sensitive immunoassays of serum proteins for high-performance detection of cancer.