Diagnostic particle agglutination using ultrasound: a new technology to rejuvenate old microbiological methods

Microbial antigen in clinical specimens can be detected rapidly by commerci al test-card latex agglutination, but poor sensitivity is a potential diffi culty, Antigen detection by immuno-agglutination of coated latex micro-part icles can be enhanced in comparison with the conventional, test-card method in both rate and sensitivity by the application of a non-cavitating ultras onic standing wave. Antibody-coated micro-particles suspended in the acoust ic field are subjected to physical forces that promote the formation of agg lutinates by increasing particle-particle contact. This report reviews the application of ultrasound to immuno-agglutination testing with several comm ercial antibody-coated diagnostic micro-particles. This technique is more s ensitive than commercial card-based agglutination tests by a factor of up t o 500 for fungal cell-wall antigen, 64 for bacterial polysaccharide and 16 for viral antigen (in buffer). The detection sensitivity of meningococcal c apsular polysaccharide in patient serum or CSF has been increased to a stag e where serotyping by ultrasound-enhanced agglutination is comparable to th at achievable with the PCR, but is available more rapidly Serum antigen con centration as measured by ultrasonic agglutination has prognostic value. In creasing the sensitivity of antigen detection by increasing the acoustic fo rces that act on suspended particles is considered. Employing turbidimetry to measure agglutination as part of an integrated ultrasonic system would e nable the turnover of large numbers of specimens. Ultrasound-enhanced latex agglutination offers a rapid, economical alternative to molecular diagnost ic methods and may be useful in situations where microbiological and molecu lar methods are impracticable.