While platelets are vital blood cells to maintain vascular integrity and foster tissue repair, unfortunately they may become ?inappropriately? activated in a wide range of disease states. To reduce this activation risk anti- thrombotic drugs are routinely prescribed to an ever increasing variety of patients, in fact being leading agents prescribed by physicians today. While these drugs are therapeutically effective they unfortunately increase the bleeding risk of the patient as a result of drug-induce platelet dysfunction. This is particularly problematic in the setting of acute illness and trauma with bleeding, when physicians need to make rapid decisions as to the effectiveness of a patient?s platelets as to coagulation competency; and the need for emergent platelet transfusions. Platelet aggregation is the tool to aid in this decision making, yet remains underutilized due to present device limitations. What is missing is a rapid, proximate, inexpensive means of assessing platelet function. Here we present a solution to this need. The UA consortium PI has led the development of clinical technologies including drug eluting stents, polymer paving, biodegradable electronics, and total artificial heart, and is a pioneer in the study of platelet mechanobiology and thrombotic mechanisms providing valuable expertise in the cardiovascular device diagnostics and therapeutics. Our described ?MICELI? (MICrofluidic, ELectrical, Impedance) aggregometer improves on current technology to measure aggregation by decreasing the footprint and complexity of the assay, its cost and overall time to perform. Current aggregometers are large, expensive and require large blood volumes and multiple processing steps. The MICELI platform works via impedance measured across 2 electrodes, submerged in platelet sample within a closed cartridge. Impedance between electrodes increases in correspondence to platelet aggregation; the impedance data are converted into aggregation values: magnitude (?), velocity (? /min), and area under the curve (??min). A small blood volume is required (250 uL) and time between blood collection and results is under 10 minutes. The accuracy and precision of the MICELI has been successfully verified against standard aggregometers with whole blood and platelet-rich plasma. The feasibility of the MICELI aggregometer has been established at a proof-of-concept level; our goal is to translate the MICELI into a clinically relevant, point-of-care device. We will achieve this objective using a disciplined design control process with specific successful completion of aims. (SA1) We will validate the MICELI using human whole blood with collagen & TRAP-6 as aggregation agonists, verifying its sensitivity and detection limits for platelet count, hematocrit and conventional antithrombotic therapies. Current impedance aggregometry methods require highly-accurate, manual adding of liquid agonist and platelet sample to the reaction chamber, introducing source of error and lack of standardization between users. Therefore, we will design an improved MICELI cartridge that allows for (SA2) lyophilization and stability of aggregation agonists and (SA3) completely enclosed reaction chamber cartridge for volume-controlled blood sample filling and precision manufactured electrodes. A successful outcome of this proposal is an inexpensive, rapid, precise, disposable, bio-stable, MICELI cartridge prototype. Commercialization of the complete MICELI aggregometer system (housing for cartridge, electronics, data processing algorithm, and user interface) is the subject of a future Phase II submission.
Exposing blood to disease, foreign material, or turbulent flow is associated with increased thrombotic complication. In these cases, clinicians administer antithrombotic drug regimens to prevent occlusive thrombosis, which while effective carries an untoward bleeding risk. When faced with trauma or acute illness these drug administered patients need rapid physician assessment of platelet function at the site of clinical decision making to reduce blood product use (transfusions) and to save lives. An equilibrium exists in the ?hemostatic state? of blood between clotting and bleeding; identifying and quantifying this ?state? can be a complicated, expensive, and time-consuming effort, risking hemorrhagic or thrombotic events in patients waiting for results. Our project seeks to further develop our prototype and design a novel point-of-care device that will make identification of this patient-specific hemostasis state faster, more user- friendly and ultimately more cost-effective, thereby positively impacting healthcare.