Vol.5 No.1 2012

Research paper : Research and development of a monopivot centrifugal blood pump for clinical use (T. Yamane et al.)−20−Synthesiology - English edition Vol.5 No.1 (2012) of 8 mm in diameter. Though the pump is made mainly of the usual material, polycarbonate, the straight path structure and the assembling method without seals or adhesive materials are the original ideas of the company.4 Role and fruits of AIST in the product design and the design verification4.1 Engineering evaluation in the laboratoryBefore the application to Pharmaceuticals and Medical Devices Agency (PMDA), the efficacy, safety, and quality designated in pharmaceutical law should be evaluated. The company was in charge of the evaluation of safety and quality. AIST was in charge of the evaluation of efficacy and conducted a flow visualization test, an in vitro thorombogenicity test, and a durability test for design evaluation.The AIST empirical standard for thrombus formation is shear rate of less than 300 s-1. As a result of flow visualization, since flow region of less than 300 s-1 was found at a sharp corner of the pivot support, a geometrical modification was performed for the corner[5][6] (Fig. 4).In the durability test the impeller axial displacement was continuously measured with a laser confocal displacement meter. It was verified that the axial wear rate of the female pivot was as small as 1.1 m/day. Though the geometry of the wear section generally becomes the letter W for rotational wear tests, the trace of wear was not observable. The operation was found to be sufficiently silent. The in vitro thrombogenic test was proposed by AIST to investigate whether thrombus forms or not before animal experiments.[7] The closed circuit including a test pump was filled with purchased bovine blood, and sodium citrate and calcium chloride were used to maintain the active clotting time (ACT) to be around 200 s and the temperature at 37 °C for two hours. As a result of this method, the thrombus induced by a small difference of male/female pivot radii was successfully removed by adjusting the radii (Fig. 5).4.2 Animal tests as M/E collaborationWe repeated more than 20 animal tests with sheep at University of Tsukuba with prototype blood pumps to eliminate thrombus and finally found no thrombus in a five-week animal experiment. The mass production models were also tested at Tohoku University and no thrombus were found in a 4-week animal test (Fig. 6). As mentioned above, the medical team advised us of the concept of evidence-based medicine, namely we do not go directly to multiple animal experiments but utilize in vitro testing to obtain scientific evidences. We conducted sufficient flow visualization experiments and in vitro thrombogenic tests and minimized the number of animal experiments. The important advice led to an efficient development and this can be regarded as the fruit of the M/E collaboration.Generally speaking, M/E collaboration has two patterns. One is where a hospital supports a company to test a product based on a company’s seed. This is because a company cannot be a user of medical products by itself. The other is where a university, a hospital, or a research facility offers a seed and a company joins to realize a product. The case presented in this paper corresponds to the latter case. Former cases of similar patterns for VADs are as follows and most of them are accomplished products:a pulsatile VAD with pneumatic driver of Xeon Medical/University of Tokyoa pulsatile VAD with pneumatic driver of Toyobo/National Cardiovascular Centera rotary VAD with a magnetic bearing of Terumo/Kyoto Universitya rotary VAD with a mechanical seal of Sun Medical Fig. 3 Difference of hemolysis levels due to difference of pivot geometries1. Indices of Monopivot Pumps(g/100L)Relative ratioHemolysis index of controlHemolysis IndexGeometryContact area, Point contactContact area 8.0 mm2Contact area 3.6 mm2Contact area 1.6 mm2dcbaFemaleMaleφ3.0φ1.4FemaleMaleφ3.0φ2.0FemaleMaleφ3.0φ2.7FemaleMaleφ3.0φ5.0


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