Hydrodynamic characteristics of the helical flow pump.

The helical flow pump (HFP) was invented to be an ideal pump for developing the TAH and the helical flow TAH (HFTAH) using two HFPs has been developed. However, since the HFP is quite a new pump, hydrodynamic characteristics inside the pump are not clarified. To analyze hydrodynamic characteristics of the HFP, flow visualization study using the particle image velocimetry and computational fluid dynamics analysis were performed. The experimental and computational models were developed to simulate the left HFP of the HFTAH and distributions of flow velocity vectors, shear stress and pressure inside the pump were examined. In distribution of flow velocity vectors, the vortexes in the vane were observed, which indicated that the HFP has a novel and quite unique working principle in which centrifugal force rotates the fluid in the helical volutes and the fluid is transferred from the inlet to the outlet helical volutes according to the helical structure. In distribution of shear stress, the highest shear stress that was considered to be occurred by the shunt flow across the impeller was found around the entrance of the inlet helical volute. However, it was not so high to cause hemolysis. This shunt flow is thought to be improved by redesigning the inlet and outlet helical volutes. In distribution of pressure, negative pressure was found near the entrance of the inlet helical volute. However, it was not high. Negative pressure is thought to be reduced with an improvement in the design of the impeller or the vane shape.

Computational fluid dynamics analysis of the pump parameters in the helical flow pump.

The helical flow pump (HFP) was invented to develop a total artificial heart at the University of Tokyo in 2005. The HFP consists of the multi-vane impeller involving rotor magnets, a motor stator and pump housing having double-helical volutes. To investigate the characteristics of the HFP, computational fluid dynamics analysis was performed. Validation of the computational model was performed with the data of the actual pump. A control computational model in which the vane area corresponded approximately to that of the actual pump was designed for the parametric study. The parametric study was performed varying the vane height, vane width and helical volute pitch. When the vane height was varied from 0.5 to 1.5 times that of the control computational model, the H-Q (pressure head vs. flow) and efficiency curves were translated in parallel with the vane height. When the vane height was two and three times that of the control computational model, the profile of these curves changed. From the results, the best proportion for the vane was considered to be a vane height between 1.5 and 2 times the vane width. The effect of vane width was not very strong compared to that of the vane height. A similar tendency in vane height was observed by varying the helical volute pitch. The best helical volute-pitch size is considered to be between 1.5 and 2 times the vane width. Although further study is necessary to determine the best values for these parameters, the characteristics of the pump parameters in the HFP could be approximately clarified.

Development of normal-suction boundary control method based on inflow cannula pressure waveform for the undulation pump ventricular assist device.

It is desirable to obtain the maximum assist without suction in ventricular assist devices (VADs). However, high driving power of a VAD may cause severe ventricle suction that can induce arrhythmia, hemolysis, and pump damage. In this report, an appropriate VAD driving level that maximizes the assist effect without severe systolic suction was explored. The target driving level was set at the boundary between low driving power without suction and high driving power with frequent suction. In the boundary range, intermittent mild suction may occur. Driving power was regulated by the suction occurrence. The normal-suction boundary control method was evaluated in a female goat implanted with an undulation pump ventricular assist device (UPVAD). The UPVAD was driven in a semipulsatile mode with heartbeat synchronization control. Systolic driving power was adjusted using a normal-suction boundary control method developed for this study. We confirmed that driving power could be maintained in the boundary range. Occurrences of suction were evaluated using the suction ratio. We defined this ratio as the number of suction occurrences divided by the number of heartbeats. The suction ratio decreased by 70% when the normal-suction boundary control method was used.

The helical flow pump with a hydrodynamic levitation impeller.

The helical flow pump (HFP) is a novel rotary blood pump invented for developing a total artificial heart (TAH). The HFP with a hydrodynamic levitation impeller, which consists of a multi-vane impeller involving rotor magnets, stator coils at the core position, and double helical-volute pump housing, was developed. Between the stator and impeller, a hydrodynamic bearing is formed. Since the helical volutes are formed at both sides of the impeller, blood flows with a helical flow pattern inside the pump. The developed HFP showed maximum output of 19 l/min against 100 mmHg of pressure head and 11 % maximum efficiency. The profile of the H-Q (pressure head vs. flow) curve was similar to that of the undulation pump. Hydrodynamic levitation of the impeller was possible with higher than 1,000 rpm rotation speed. The normalized index of the hemolysis ratio of the HFP to centrifugal pump (BPX-80) was from 2.61 to 8.07 depending on the design of the bearing. The HFP was implanted in two goats with a left ventricular bypass method. After surgery, hemolysis occurred in both goats. The hemolysis ceased on postoperative days 14 and 9, respectively. In the first experiment, no thrombus was found in the pump after 203 days of pumping. In the second experiment, a white thrombus was found in the pump after 23 days of pumping. While further research and development are necessary, we are expecting to develop an excellent TAH with the HFP.

Results of animal experiments with the fourth model of the undulation pump total artificial heart.

Animal experiments using a total artificial heart in a goat are not easy to perform. The fourth model of the undulation pump total artificial heart (UPTAH4), which was designed to perform a long-term physiological experiment including pulsatile and nonpulsatile TAH operations with a conductance- and arterial pressure-based control method named 1/R control, was implanted in 31 goats weighing 38.5 to 60.4 kg (average of 46.8 kg). The 1/R control is a physiological flow control method of TAH developed with a conductance (1/R: reciprocal of a resistance) parallel circuit model. The survival periods were from 0.1 to 153 days (average of 14.5 days). The causes of termination were postoperative bleeding in eight goats, respiratory failure in five goats, device failure in 14 goats, dissected aneurysm in two goats, and thrombus in one goat. The thrombus case was the longest surviving goat. The respiratory failure tended to occur when the extracorporeal circulation time was prolonged. Autotransfusion was effective for the prolongation of survival time. The left-right balance control and the suction control were performed successfully in all goats. The 1/R control was performed for a long time in five goats that survived for more than 1 month. With three goats that survived for 48, 52, and 53 days mainly with the pulsatile mode, the 1/R control was stable. With a goat that survived for 73 days, the nonpulsatile mode with the 1/R control could be tested for 3 weeks. With the longest surviving goat that was maintained mainly with the pulsatile mode, the 1/R control was unstable, possibly due to the mismatching of the response time of the control system between the computer and the body. However, liver and kidney functions were almost normal, and the total protein level recovered. Further study to stabilize the 1/R control in the UPTAH is necessary.

Automatic calibration of the inlet pressure sensor for the implantable continuous-flow ventricular assist device.

Significant progress in the development of implantable ventricular assist devices using continuous-flow blood pumps has been made recently. However, a control method has not been established. The blood pressure in the inflow cannula (inlet pressure) is one of the candidates for performing an adequate control. This could also provide important information about ventricle sucking. However, no calibration method for an inlet pressure sensor exists. In this study, an automatic calibration algorithm of the inlet pressure sensor from the pressure waveform at the condition of ventricle sucking was proposed. The calibration algorithm was constructed based on the consideration that intrathoracic pressure could be substituted for atmospheric pressure because the lung is open to air. We assumed that the inlet pressure at the releasing point of the sucking would represent the intrathoracic pressure, because the atrial pressure would be low owing to the sucking condition. A special mock circulation system that can reproduce ventricle sucking was developed to validate the calibration algorithm. The calibration algorithm worked well with a maximum SD of 2.1 mmHg for 3-min measurement in the mock circulation system. While the deviation was slightly large for an elaborate calibration, it would still be useful as a primitive calibration. The influence of the respiratory change and other factors as well as the reliability of the calibration value should be investigated with an animal experiment as a next step.

Use of in vivo insert molding to form a jellyfish valve leaflet.

We developed an in vivo insert molding technique to form tissue-derived biomaterials into the desired shape, and with sufficient strength and durability, for use in artificial organs. Molds of acrylic resin with inserted velour cloth were implanted under the skin of goats to form a circular leaflet for a jellyfish valve. The valve leaflets were successfully produced in the molds after 17-60 days. Dense connective tissue covered the velour cloth, and loose connective tissue was formed within it. Tissue was radially formed from the hole in the mold. The tissue was simultaneously formed and shrunk. It is necessary to increase the connected portion between the tissue inside and outside the mold so that the tissue can completely cover the inserted materials without shrinkage.

A nonpulsatile total artificial heart with 1/R control.

A total artificial heart (TAH) using continuous flow pumps is promising for size reduction of the device; however, the role of pulsatility in TAHs has been a subject of great debate. Additionally, it is unclear whether, in a nonpulsatile TAH, a physiological control method such as 1/R control can keep the experimental animal in good condition. To realize a nonpulsatile TAH with 1/R control, the artificial valves were removed from undulation pump total artificial hearts (UPTAHs), which can produce both pulsatile and nonpulsatile flows using a single device. The UPTAHs were implanted into 18 goats, and 4 goats survived for more than 1 month. Three weeks of long-term nonpulsatile TAH operation could be tested in the goat that survived for 72 days, and it was proved that 1/R control is possible not only with a pulsatile TAH but also with a nonpulsatile TAH. The general condition of the goat and its organ function did not change on the application of nonpulsatile mode. Cardiac output and arterial pressure changed with the condition of the goat in pulsatile and also in nonpulsatile modes, and the changes seemed almost identical. However, the sucking effect of the atria was very significant in nonpulsatile mode, resulting in hemolysis. Therefore, nonpulsatile TAHs under 1/R control are considered to be inadequate unless some pulsatility can be introduced to avoid fatal sucking effects and to ensure sufficient inflow. During nonpulsatile operation, regular fluctuations were sometimes found in the aortic pressure, and these were caused by the periodic sucking effect in the left atrium that was possibly influenced by respiratory changes.

Relation between left atrial pressure and the corresponding pulse pressure in the helical flow total artificial heart.

The present control method used in our helical flow total artificial heart (HFTAH) would only need four parameters. Nowadays, gauge pressure sensors are being used to obtain the pressure needed for control parameters. Nevertheless, there are also many following problems such as calibration, maintenance, offset drift and infection due to the skin-penetrative lines for the usage of gauge pressure sensor. Therefore, it is preferable to find another substitutional way instead of the gauge sensor to measure the pressure. In addition, with an eye to completing an implantable HFTAH, we would like to do without any lines through the experiment animal. Therefore, it was confirmed in this study that whether there is a relation between the left atrial pressure (LAP) and its pulse pressure (amplitude). Subsequently the mean value of LAP and its amplitude were quantified. There are two methods used in this study to process the data. Method one, frequency spectrum analysis, is to quantify the signals by getting the absolute value of amplitude for a fixed heartbeat analysis. Method two, by using the synchronous detection method, it is postulated to be more applicable to variant heartbeat data with 1/R control. By the relation of LAP and the pulse pressure acquired in the above two methods, as long as the amplitude of LAP is known by the absolute pressure sensor, it's able to obtain the mean value of LAP (for it suggests a linear relation). Therefore the characteristic could substitute one of the control parameter (that is the LAP), and the other three parameters will be acquired by estimation thus it doesn't need to measure them additionally. Consequently, it is expected that acquiring LAP by absolute pressure sensor for one of the control parameters could attain to an implantable HFTAH.

The helical flow total artificial heart: implantation in goats.

To realize a total artificial heart (TAH) with high performance, high durability, good anatomical fitting, and good blood compatibility, the helical flow TAH (HFTAH) has been developed with two helical flow pumps having hydrodynamic levitation impeller. The HFTAH was implanted in goats to investigate its anatomical fitting, blood compatibility, mechanical stability, control stability, and so on. The size of the HFTAH was designed to be 80 mm in diameter and 84 mm wide. The maximum output was 19 L/min against 100 mmHg of pressure head. Eight adult female goats weighting from 45 to 56.3 kg (average 49.7 kg) were used. Under the extracorporeal circulation, natural heart was removed at the atrioventricular groove and the HFTAH was implanted. The HFTAH was driven with a pulsatile mode. The 1/R control was applied when the right atrial pressure recovered. The HFTAH could be implanted with good anatomical fitting in all goats. Two goats survived for more than a week. One goat is ongoing. Other goats did not survive for more than two days with various reasons. In the goats that survived for more than a week, the hydrodynamic bearing was worn and broken, which indicated that the bearing touched to the shaft. The cause was supposed to be the influence of the sucking effect. The potential of the HFTAH could be demonstrated with this study. The stability of the hydrodynamic bearing in a living body, especially the influence of the sucking effect, was considered to be very important and a further study should be necessary.

Pulsatile driving of the helical flow pump.

The helical flow pump (HFP) is newly developed blood pomp for total artificial heart (TAH). HFP can work with lower rotational speed than axial and centrifugal blood pump. It can be seen reasonable feature to generate pulsatile flow because high response performance can be realized. In this article, pulsatility of HFP was evaluated using mock circulation loop. Pulsatile flow was generated by modulating the rotational speed in various amplitude and heart rate. In the experiment, relationship between Pump flow, pump head, rotational speed amplitude, heart rate and power consumption is evaluated. As the result, complete pulsatile flow with mean flow rate of 5 L/min and mean pressure head of 100 mmHg can be obtained at ± 500 rpm with mean rotational speed of 1378 to 1398 rpm in hart rate from 60 to 120. Flow profiles which are non-pulsatile, quasi-pulsatile or complete flow can be adjusted arbitrarily. Therefore, HFP has excellent pulsatility and control flexibility of flow profile.

Development of a durable fiber-optic oxygen sensor for harsh underground environments.

This paper focuses on effects of protection with a silicone resin to develop a fiber-optic oxygen sensor with long-term stability and durability in harsh underground environments. Ruthenium (II) complexes were used as oxygen-sensing compounds. A uniform composite film composed of silicone resin and the Ru complex was prepared with spin coating technique. A comparison of dissolved-oxygen (DO) sensitivity between the composite film and a Ru complex film was made by exposing to hot water (80 degrees C). The result of the accelerated degradation test showed that sensitivity of the Ru complex film was stable; meanwhile that of the composite film increased with exposure time in a short period. In order to improve stability, the Ru complex film overcoated with silicone resin was prepared. Differences in sensitivity for saturated DO (8.5 ppm) between with and without the silicone resin overcoating on the Ru complex film were investigated by exposing to the hot water and simulated underground water. These results revealed that the sensitivities and response times of the overcoated films were stable and slow, respectively, compared to those of non-overcoated films. Then, optodes were evaluated for effects of the overcoating on sensing properties by exposing to 100 vol.% oxygen gas. The experiment showed that: (1) the response time was significantly influenced by the thickness of the overcoating; and (2) response speed of the overcoated optode was slow by a factor of about 35 compared to that of the non-overcoated. We concluded that the overcoating was effective in the application to mid- and long-term oxygen monitoring in the harsh environments.

Preliminary study of physiological control for the undulation pump ventricular assist device.

The undulation pump ventricular assist device (UPVAD) is a small implantable ventricular assist device using an undulation pump. The UPVAD can produce pulsatile flow by changing the motor rotation speed of the UPVAD. Because the undulation pump is a volume displacement type pump, the inflow sucking occurs easily. The purpose of this study is to develop a suitable control method for the UPVAD. The UPVAD inflow cannula equipped with an implantable pressure sensor was inserted into the ventricle. Therefore, pressure variation that synchronized with the natural heartbeat and negative pressure spike caused the inflow sucking were observed. By changing the motor rotation speed that responded to the inflow pressure, the UPVAD could synchronize with the natural heartbeat and the UPVAD could generate a co-pulse assist flow. The inflow sucking could be released by reducing the motor rotation speed, if the inflow sucking was detected. The newly developed control method exhibited superior characteristics than existing ones due to high immunity against pressure sensor drift. The assist flow could be increased more than 15% and the inflow sucking occurrence could be decreased with this control method. The UPVAD could generate the suitable assist flow with the developed control method.

Development of a three-dimensional bioprinter: construction of cell supporting structures using hydrogel and state-of-the-art inkjet technology.

We have developed a new technology for producing three-dimensional (3D) biological structures composed of living cells and hydrogel in vitro, via the direct and accurate printing of cells with an inkjet printing system. Various hydrogel structures were constructed with our custom-made inkjet printer, which we termed 3D bioprinter. In the present study, we used an alginate hydrogel that was obtained through the reaction of a sodium alginate solution with a calcium chloride solution. For the construction of the gel structure, sodium alginate solution was ejected from the inkjet nozzle (SEA-Jet, Seiko Epson Corp., Suwa, Japan) and was mixed with a substrate composed of a calcium chloride solution. In our 3D bioprinter, the nozzle head can be moved in three dimensions. Owing to the development of the 3D bioprinter, an innovative fabrication method that enables the gentle and precise fixation of 3D gel structures was established using living cells as a material. To date, several 3D structures that include living cells have been fabricated, including lines, planes, laminated structures, and tubes, and now, experiments to construct various hydrogel structures are being carried out in our laboratory.

Fundamental study to develop a fiber-optic gap sensor for a rotary undulation pump.

The rotary undulation pump is believed to be a good candidate for the next-generation artificial heart. Due to its complex movement, it is desirable to magnetically levitate the rotor and dynamically control the gap. In this article, the applicability of a fiber-optic gap sensor to the dynamic position control of the rotor in the rotary undulation pump was investigated. The fiber-optic gap sensor consisted of two plastic-core fibers and a reflection plate. Two 1-mm-diameter optical fibers were aligned parallel: one for source light propagation and the other for reflected light transmission. The basic properties of gap sensors using four different light sources were explored in five media (air, physiologic saline, and blood samples with three different hematocrit levels). The influence of the oxygen saturation level in the blood on sensing was investigated with two types of light sources. It is desirable to use a light source the wavelength of which shows similar absorption coefficients for both oxygenated blood and deoxygenated blood. The effect of the distance between the two fibers on the sensing and range was also investigated. The results indicated that the fiber-optic gap sensor is quite promising for the active control of rotor positioning in the rotary undulation pump.

Development of mechanical circulatory support devices at the University of Tokyo.

The development of mechanical circulatory support devices at the University of Tokyo has focused on developing a small total artificial heart (TAH) since achieving 532 days of survival of an animal with a paracorporial pneumatically driven TAH. The undulation pump was invented to meet this purpose. The undulation pump total artificial heart (UPTAH) is an implantable TAH that uses an undulation pump. To date, the UPTAH has been implanted in 71 goats weighting from 39 to 72 kg. The control methods are very important in animal experiments, and sucking control was developed to prevent atrial sucking. Rapid left-right balance control was performed by monitoring left atrial pressure to prevent acute lung edema caused by the rapid increase in both arterial pressure and venous return associated with the animal becoming agitated. Additionally, 1/R control was applied to stabilize the right atrial pressure. By applying these control methods, seven goats survived more than 1 month. The maximum survival period was 63 days. We are expecting to carry out longer term animal experiments with a recent model of TAH. In addition to the TAH, an undulation pump ventricular assist device (UPVAD), which is an implantable ventricular assist device (VAD), has been in development since 2002, based on the technology of the UPTAH. The UPVAD was implanted in six goats; three goats survived for more than 1 month. While further research and development is required to complete the the UPVAD system, the UPVAD has good potential to be realized as an implantable pulsatile-flow VAD.

Progress in the control system of the undulation pump total artificial heart.

The undulation pump total artificial heart (UPTAH) is a small implantable total artificial heart. As the UPTAH generates outflow and inflow at the same time, control of the UPTAH is very difficult. Therefore suitable control methods specifically for the UPTAH should be established. Various motor control, left-right flow balance control, and physiological control methods were examined and tried for the UPTAH control in this study. The control system is divided into seven categories. It has a hierarchical structure and all control modes work at the same time. The UPTAH with the newly developed control method has been implanted into the chest cavities of 48 goats. Until now, six goats survived for more than one month, including 63 days in the longest case. The good condition of the UPTAH implanted animal could be maintained with the newly developed control scheme, consisting of the 1/R control and several other additional controls.