Sub-micron particle manipulation in an ultrasonic standing wave: Applications in detection of clinically important biomolecules

Separation of particles from the suspending phase is of interest, among others, to clinical analysts. A system that enables manipulation of sub-micron sized particles in suspensions of analytical scale volume (10-50 mul) using a non-cavitating ultrasonic standing wave is described. Particle suspensions, contained in glass capillary tubes of 1-2 mm internal dimension, are treated on the axis of a tubular transducer generating a radial standing wave field at 4.5 MHz. Microparticles (of average diameter range 0.3-10 mum) suspended in buffer are concentrated within seconds at preferred regions separated by submillimetre distances. Concentration of suspended latex particles was inhibited in solutions containing protein at levels similar to those occurring in clinical specimens when the suspensions were sonicated in capillaries of circular cross-section. This effect was associated with acoustic streaming of the suspending fluid. Silica microparticles (more dense and less compressible than latex) could be concentrated in the presence of streaming. Latex particles concentrated readily in square cross-section capillaries where no streaming was observed. With sub-micron particles, the geometry of the sample chamber, the suspending phase composition and the size, density and compressibility of the microparticles all influence particle manipulation. The radial standing wave system has been used to enhance agglutination of antibody-coated latex microparticles in the presence of antigen allowing rapid and highly sensitive detection of clinically important biomolecules. The sensitivity of conventional diagnostic tests for microbial antigen has been improved by application of ultrasound and clinical utility has been demonstrated, in particular, for detection of meningitis-causing bacteria.