In vivo probes: problems and perspectives

Devices constructed for potential use as invasive bioprobes incorporate a selective receiving site for molecular or ionic recognition, and a transducer which is capable of translating a perturbation of physical chemistry of the determinant-site reaction (interaction) into a usable signal. Four types are envisioned--implants for general hospital use, transient-use probes to replace classical blood tests, short-term implantable probes and the long-term variety. Performance criteria are selectivity, sensitivity, fast response, site-reversible, small, rugged, inexpensive, biocompatible, calibratible, facile use by non-expert personnel and ease of telemetry. These demands, not surprisingly, create enormous challenges to the sensor specialist. With respect to biocompatibility the sensor must not be involved in infection, clot formation or antigenic response, and, furthermore, protein adsorption, etc., which can affect the sensor response should be avoided. Calibration remains a problem of monumental proportions. Many devices drift from calibrated levels even in in vitro experiments, let alone in the implanted milieu. One solution has been to carry out on-line switching between patient blood and standard solutions. However, this type of approach leaves a lot to be desired with respect to portability. Another method which is attracting increasing attention is the chemometric or artificial intelligence system involving compensation by multi-sensor array configurations. Sensitivity and limit-of-detection have attracted little research due to the overwhelming nature of other difficulties. In the present paper we evaluate a number of these technical problems and discuss the architecture of devices that are currently available. Finally, some thoughts as to priorities for re-directing sensor research in the bioprobe area are presented.