Direct detection of tuberculosis infection in blood serum using three optical label-free approaches

We describe a new and rapid method for diagnosing tuberculosis-specific antibodies in undiluted human blood serum by surface sensitive biosensors. An integrated optical grating coupler, an interferometric biosensor and a device based on the reflectometric interference spectroscopy (BIAffinity, Analytik Jena AG) were used to determine tuberculosis-specific antibodies, which are present in blood serum of infected persons. The specific sensor surface was generated by immobilized 38-kDa tuberculosis antigen and real-time detection was performed without any label in all cases. Unspecific binding effects caused by serum proteins were suppressed by appropriate coupling chemistry. 1,4-Phenylenediisothiocyanate was used as a crosslinker for the coupling of the antigen achieving the effect of complete surface coverage. This enables label-free serodiagnosis of tuberculosis infection with a specificity of 100% and a sensitivity of 75%. Based on our results, we anticipate that a label-free detection procedure with one or more marker antigens is possible for a rapid, economical and accurate routine diagnosis of tuberculosis and other infectious diseases in the future. (c) 2007 Elsevier B.V. All rights reserved.