REMOTE MONITORING OF PROTEINS INVOLVED IN COAGULATION

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The blood response to implanted materials and devices is very difficult to monitor. One must either take periodic blood samples (using experienced personnel and very well-defined protocols to minimize artifacts) or use systemically-delivered labelled components to obtain radiographic images, using cine-radiography. The only on-line remote sensors available today include catheter tip blood gas sensors (1) and the light scattering embolus detector (2). Ideally a set of special sensors could monitor the hemostatic situation in animals and patients fitted with in vivo or ex vivo devices, analagous to the pressure and flow sensors in wide use today. We propose to study and to begin the development of specific biochemical sensors which could be used remotely, semicontinuously, and easily for extended periods to provide monitoring of the hemostatic state of patients and of experimental animals with cardio vascular implants. We propose to study a fiber optic sensor based on immobilized monoclonal antibodies (3,4). Specifically we will focus on remote immunosensors to measure antithrombin III and prothrombin. Prothrombin and antithrombin III are selected because of their importance in hemostasis and our experience with these two proteins. The development and study of successful sensors for prothrombin and antithrombin III will provide the experience and technology base for the study of sensors for other components in hemostasis. The research group's long range goal (not proposed herein) is to develop a full hemostatic screen using a multichannel fiber optic device which will provide true multichannel detection, remotely and at least semicontinuously. The availability of such sensors would significantly enhance the study of blood interactions with cardiovascular and related devices. This proposal is a resubmission. The original application was criticized as too broad and diffuse. This application is focused on two available and important coagulation proteins which provide a practical model system for studying the remote sensor concepts.