In luminescence-based ultrasensitive analysis, such as single-molecule detection by flow cytometry, the luminescence background from impurities present in the solvent or reagents can ultimately determine the detection limits. A simple, versatile method for reducing luminescence background is described. The method is based on photobleaching the reagent stream immediately before it enters the detection flow cell. Dramatic reduction (an order of magnitude or more) of both low-level continuous background and single-molecule fluorescence bursts is demonstrated. Application and enhancements of the technique are discussed.

We have developed a near-field scanning optical microscope with the sensitivity to detect single fluorescent molecules. Our microscope is based on scanning a sample under a tapered and metal coated fiber optic probe and has an illumination-aperture diameter as small as 100 nm. The microscope simultaneously acquires a shear force image with a height noise of {approximately} 1 nm. We have used this system to demonstrate the detection of single molecules of Rhodamine-6G on silica. In this paper, we explore the use of NSOM for investigations of biological molecules. We have prepared and imaged double-stranded DNA intercalated with thiazole orange homodimer (TOTO); single chromosomes stained with propidium iodide; and {beta}-phycoerythrin proteins on dry, borosilicate-glass surfaces. At very dilute coverages, isolated fluorescent spots are observed for the un-intercalated TOTO dye and for {beta}-phycoerythrin. These fluorescent spots exhibit-emission intensity fluctuations and abrupt bleaching transitions, similar to the intensity behavior observed previously for single Rhodamine 6G molecules on silica.

The development of our rapid, continuous DNA sequencing technology, based on single molecule detection of fluorescently-tagged nucleotides, has proceeded along separate research fronts, each with specific goals: the faithful replication of long sequences of template DNA using one or more fluorescent nucleotide analogues, the incorporation and stable mounting of a single DNA strand into a flow chamber, the enzymatic cleavage of labeled DNA by exonucleases, and the detection of single fluorescent nucleotides in a flow stream by the method of time-gated photon counting. Each individual goal of the sequencing technology has now been realized, and we have begun integrating these efforts in order to demonstrate the feasibility of flow-based sequencing. We are currently detecting photon bursts from TRITC labeled nucleotides which have been cleaved from DNA suspended in our flow cell. The sample size is estimated to be tens of DNA strands.

We are developing a laser-based technique for the rapid sequencing of large DNA fragments (several kb in size) at a rate of 100 to 1000 bases per second. Our approach relies on fluorescent labeling of the bases in a single fragment of DNA, attachment of this labeled DNA fragment to a support, movement of the supported DNA into a flowing sample stream, sequential cleavage of the end nucleotide from the DNA fragment with an exonuclease, and detection of the individual fluorescently labeled bases by laser-induced fluorescence.

The reconciliation of quantum mechanics and gravity on varying distance scales requires changes to General Relativity that may have testable implications. We briefly review the status of tests with matter of the inverse square law and the principle of equivalence, then report on progress on the drift-tube measurement section of PS-200, the experiment to measure the gravitational acceleration of antiprotons.

A measurement of the acceleration of antiprotons in the Earth's gravitational field was proposed to C.E.R.N. in 1986 and was accepted as experiment PS200 for operation at LEAR. In preparation for this experiment up to 50,000 antiprotons have been captured into a large Penning trap and stored for several minutes. This paper describes the experimental technique used and possible improvements in the total number of particles captured and the storage time achieved. We also discuss the current status of the development of the gravity experiment.

We have conducted a systematic study of the performance of a microchannel plate at cryogenic temperatures, and in a magnetic field perpendicular to the plate surface of up to 2.5 T. We observe no change in the characteristic pulse height distribution down to temperatures near 4 K if the count rate is kept sufficiently low. With increasing count rates the onset of saturation effects can be observed to be temperature dependent. For the specific plate used, this occurs around 1 kHz at the lowest temperature. This behavior is in good agreement with calculations based on a widely used model for the gain function of microchannel plates, if the plate resistance is allowed to be temperature dependent. Additionally we have studied the detection efficiency for low energy hydrogen ions of a chevron type microchannel plate under a variety of operating conditions at room temperature, and find the detection efficiency to level off around 60% at energies above 1 keV, if the plate is operated in a saturated gain mode.