Abstract: A method for DNA sequencing, and particularly for sequencing of the entire human genome. Different base-specific reactions are utilized to use different sets of DNA fragments from a piece of DNA of unknown sequence. Each of the different sets of DNA fragments has a common origin and terminates at a particular base along the unknown sequence. The molecular weight of the DNA fragments in each of the different sets is detected by a matrix assisted laser absorption mass spectrometer to determine the sequence of the different bases in the DNA. The methods and apparatus of the present invention provide a relatively simple and low cost technique which may be automated to sequence thousands of gene bases per hour, and eliminates the tedious and time consuming gel electrophoresis separation technique conventionally used to determine the masses of DNA fragments.

Abstract: A mass analyzer for the analysis of mass spectra of ions derived from organic molecules includes an electrospray ion source having means to transport the molecules of interest in a solvent of pure water free of organic solvents. The electrospray ion source sprays the water solution, under an imposed voltage, through a metal syringe needle having a sharp etched point and into a conductive capillary tube having a sharpened entrance orifice.

Abstract: In mass spectrometry, a time of flight (TOF) mass spectrometer is used to measure the mass spectrum of organic molecules of mass ranging from 200 Dalton to greater than 200,000 Dalton. Ions from the sample are desorbed by striking the probe tip with laser pulses in a spot size, on the tip, in the range of 0.03-3.0 mm.sup.2. The time of flight of the ions is measured and displayed with a resolution of the ion molecular signal in the range of 300-500 full width at half-maximum definition (FWHM).

Abstract: An electrospray ion source is designed for ready and simple plugging into commercial mass analyzers for mass spectrometric analysis of organic molecules. The electrospray is carried out is the ambient air and the ions and other charged species enter the mass analyuzer through a long metal capillary tube and three stages of differential pumping. The use of the long tube allows (a) convenient injection of the ions into the mass analyzer (b) optimization of the spray by direct visualization in the air (c) efficient and controlled heat transfer to the droplets and (d) efficient pumping of the region between the capillary exit and the skinner. Desolvation of the solvated ions is carried out using a combination of controlled heat transfer to the charged droplets during the transit through the tube and collisional activation in a region of reduced pressure. Desolvation with this system does not involve use of a strong countercurrent flow of heated gas.