Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.

BACKGROUND: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. METHODS: This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). RESULTS: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. CONCLUSIONS: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.

CMIC: predicting DNA methylation inheritance of CpG islands with embedding vectors of variable-length k-mers.

BACKGROUND: Epigenetic modifications established in mammalian gametes are largely reprogrammed during early development, however, are partly inherited by the embryo to support its development. In this study, we examine CpG island (CGI) sequences to predict whether a mouse blastocyst CGI inherits oocyte-derived DNA methylation from the maternal genome. Recurrent neural networks (RNNs), including that based on gated recurrent units (GRUs), have recently been employed for variable-length inputs in classification and regression analyses. One advantage of this strategy is the ability of RNNs to automatically learn latent features embedded in inputs by learning their model parameters. However, the available CGI dataset applied for the prediction of oocyte-derived DNA methylation inheritance are not large enough to train the neural networks. RESULTS: We propose a GRU-based model called CMIC (CGI Methylation Inheritance Classifier) to augment CGI sequence by converting it into variable-length k-mers, where the length k is randomly selected from the range [Formula: see text] to [Formula: see text], N times, which were then used as neural network input. N was set to 1000 in the default setting. In addition, we proposed a new embedding vector generator for k-mers called splitDNA2vec. The randomness of this procedure was higher than the previous work, dna2vec. CONCLUSIONS: We found that CMIC can predict the inheritance of oocyte-derived DNA methylation at CGIs in the maternal genome of blastocysts with a high F-measure (0.93). We also show that the F-measure can be improved by increasing the parameter N, that is, the number of sequences of variable-length k-mers derived from a single CGI sequence. This implies the effectiveness of augmenting input data by converting a DNA sequence to N sequences of variable-length k-mers. This approach can be applied to different DNA sequence classification and regression analyses, particularly those involving a small amount of data.

In vitro hemocompatibility investigation for the development of low-flow centrifugal blood pumps with less platelet clogging.

Low-flow blood pumps rated under 1 L/min are emerging for new medical applications, such as hemofiltration in acute use. In those pumps, platelet adhesion and aggregation have to be carefully considered because of clogging risk in the filter part. To find an acceptable hemocompatibility that can be applied to low-flow centrifugal blood pump design, the platelet aggregation index, clogging on a micromesh filter, and the hemolysis index were investigated using a low-flow blood pump designed for hemofiltration use. We conducted circulation testing in vitro using fresh porcine blood and two centrifugal pumps with different impeller inlet shapes. The Negative Log Platelet Aggregation Threshold Index (NL-PATI), which reflects the ability of residual platelets to aggregate, and flow rate were measured during reflux for 60 min, and the Normalized Index of Hemolysis (NIH (g/20 min)) was calculated. In addition, blood cell clogging after reflux was observed on the micromesh filter by SEM, and the adhesion rate was calculated. Our results showed that the platelet clogging on the micromesh filter occurred when the average NL-PATI was greater than 0.28 and the average NIH (g/20 min) was greater than 0.01. In contrast, platelet clogging on the micromesh was suppressed when NL-PATI was less than 0.17 and the NIH (g/20 min) was less than 0.003. These values might be used as acceptable hemocompatibility of low-flow centrifugal blood pumps with suppressed platelet clogging for hemofiltration pumps.

Individual Variability in von Willebrand Factor Fragility in Response to Shear Stress: A Possible Clue for Predicting Bleeding Risk.

Acquired von Willebrand syndrome (AVWS), characterized by reduced von Willebrand factor (VWF) large multimers, has recently been implicated as the principal mechanism underlying bleeding in patients implanted with left ventricular assist devices (LVADs). Hematological severity of AVWS varies among patients, even if an identical device is implanted. We investigated whether this diversity in hematological severity is due to individual variability in VWF fragility, according to responses to incremental shear stress. Whole-blood samples were sheared at 20,000-40,000 s -1 shear rate, an index of shear stress, using a custom-made shear stressor that could generate shear stress compatible with that produced by an LVAD. The degree of VWF large multimers degradation was evaluated using the VWF large multimer index. A significant inverse correlation was observed between the VWF large multimer index and LVAD-compatible magnitudes of shear stress: the VWF large multimer indices were 68.5 ± 18.3, 48.0 ± 13.9, 33.9 ± 12.1, 23.7 ± 7.9, and 18.7% ± 8.7% at 20,000, 25,000, 30,000, 35,000, and 40,000 s -1 of shear rates, respectively ( P < 0.0001). Furthermore, experimental VWF large multimer index values were compatible with those derived from patients with implanted LVADs (median; 28.9%). Finally, reduction in the VWF large multimer index corresponding to shear stress showed individual variation. We demonstrated that the combined use of a novel high shear stress loading device and quantitative evaluation of VWF large multimers may predict risk of bleeding before LVAD implantation.

A convolutional neural network-based regression model to infer the epigenetic crosstalk responsible for CG methylation patterns.

BACKGROUND: Epigenetic modifications, including CG methylation (a major form of DNA methylation) and histone modifications, interact with each other to shape their genomic distribution patterns. However, the entire picture of the epigenetic crosstalk regulating the CG methylation pattern is unknown especially in cells that are available only in a limited number, such as mammalian oocytes. Most machine learning approaches developed so far aim at finding DNA sequences responsible for the CG methylation patterns and were not tailored for studying the epigenetic crosstalk. RESULTS: We built a machine learning model named epiNet to predict CG methylation patterns based on other epigenetic features, such as histone modifications, but not DNA sequence. Using epiNet, we identified biologically relevant epigenetic crosstalk between histone H3K36me3, H3K4me3, and CG methylation in mouse oocytes. This model also predicted the altered CG methylation pattern of mutant oocytes having perturbed histone modification, was applicable to cross-species prediction of the CG methylation pattern of human oocytes, and identified the epigenetic crosstalk potentially important in other cell types. CONCLUSIONS: Our findings provide insight into the epigenetic crosstalk regulating the CG methylation pattern in mammalian oocytes and other cells. The use of epiNet should help to design or complement biological experiments in epigenetics studies.

Quantitative investigation of platelet aggregation under high shear force for anti-platelet aggregation in vitro tests.

Blood pumps are often used for hemofiltration in patients with renal failure. To design effective centrifugal blood pumps for hemofiltration, it is important to suppress clogging caused by platelet aggregation. However, the optimal conditions for conducting anti-platelet aggregation tests in vitro have not yet been established. This study aimed to quantify the effect of the shear loading value and shear loading time on platelet aggregation and determine the optimal conditions for anti-platelet aggregation testing in vitro. To quantitatively evaluate platelet aggregation in terms of the negative logarithm-platelet aggregation threshold index (NL-PATI), which reflects the propensity of residual platelets to aggregate after shear loading, the following parameters were examined: blood collection method (collected from porcine vein using a syringe or collected from a slaughterhouse), type of anticoagulant (sodium citrate or heparin), shear rate, and shear time. The results showed that platelet aggregation in porcine blood increased under a high shear load applied at shear rates of approximately 20,000 s-1 or higher for 30 s. Platelet aggregation propensity was 2-3 times higher in heparin-anticoagulated blood than in sodium citrate-anticoagulated blood. Moreover, platelet aggregation was 1.5-2 times more in blood collected from the slaughterhouse than in syringe-collected blood. Testing with an integrated shear time of 30 s or less in relation to the total blood volume may be effective for conducting in vitro circulation experiments using hemofiltration blood pumps. The conditions established in this study may be useful for hemocompatibility testing of cardiovascular devices based on NL-PATI.

Improvement of hemolysis performance in a hydrodynamically levitated centrifugal blood pump by optimizing a shroud size.

We have developed a hydrodynamically levitated centrifugal blood pump. In the blood pump having hydrodynamic bearings, the narrow bearing gap has a potential for high hemolysis. The purpose of the this study is to improve hemolysis performance in a hydrodynamically levitated centrifugal blood pump by optimizing a shroud size. The impeller was levitated passively at the position where the thrust forces acting on the impeller were balanced. We focused on a size of a bottom shroud with a hydrodynamic bearing that could change the bottom hydrodynamic force to balance the thrust force at the wide bearing gap for reducing hemolysis. Five test models with various shroud size were compared: 989 mm2 (HH-10.5), 962 mm2 (HH-12), 932 mm2 (HH-13.5), 874 mm2 (HH-16), and 821 mm2 (HH-18). A numerical analysis was first performed to estimate the bearing gaps in the test model. The bearing gaps were then measured to validate the numerical analysis. Finally, an in vitro hemolysis test was performed. The numerical analysis revealed that the HH-13.5 model had the widest bearing gap of 129 µm. In the measurement test, the estimation error for the bearing gap was less than 10%. In the hemolysis test, the HH-13.5 model achieved the lowest hemolysis level among the five models. The present study demonstrated that the numerical analysis was found to be effective for determining the optimal should size, and the HH-13.5 model had the optimal shroud size in the developed hydrodynamically levitated centrifugal blood pump to reduce hemolysis.

Real-time, non-invasive thrombus detection in an extracorporeal circuit using micro-optical thrombus sensors.

INTRODUCTION: Real-time, non-invasive monitoring of thrombus formation in extracorporeal circuits has yet to be achieved. To address the challenges of conventional optical thrombus detection methods requiring large devices that limit detection capacity, we developed a micro-optical thrombus sensor. METHODS: The proposed micro-optical thrombus sensor can detect the intensity of light scattered by blood at wavelengths of 660 and 855 nm. Two thrombus sensors were installed on in vitro circuit: one at the rotary blood pump and one at a flow channel. To evaluate the variation in the ratio of incident light intensity at each wavelength of the two sensors, Rfluct (for 660 nm) and Ifluct (for 855 nm) were defined. Using fresh porcine blood as a working fluid, we performed in vitro tests of haematocrit (Hct) and oxygen saturation (SaO2) variation and thrombus detection. Thrombus tests were terminated after Rfluct or Ifluct showed a larger change than the maximum range of those in the Hct and SaO2 variation test. RESULTS: In all three thrombus detection tests, Ifluct showed a larger change than the maximum range of those in the Hct and SaO2 variation test. After the tests, thrombus formation was confirmed in the pump, and there was no thrombus in the flow channel. The results indicate that Ifluct is an effective parameter for identifying the presence of a thrombus. CONCLUSION: Thrombus detection in an extracorporeal circuit using the developed micro-optical sensors was successfully demonstrated in an in vitro test.

Suitable hemolysis index for low-flow rotary blood pumps.

A suitable index is needed for hemolysis tests that use low-flow pumps, such as pediatric blood pumps or blood purification pumps. To create such an index, the present study investigates the change of plasma-free hemoglobin in the pump circuit with time and the change of the hemolysis rate with flow rate and impeller rotational speed. The results show that the hemolysis rate or the increase rate of the total free hemoglobin are suitable measures for hemolysis evaluation for low-flow pumps.

Plasma skimming efficiency of human blood in the spiral groove bearing of a centrifugal blood pump.

This work investigates the plasma skimming effect in a spiral groove bearing within a hydrodynamically levitated centrifugal blood pump when working with human blood having a hematocrit value from 0 to 40%. The present study assessed the evaluation based on a method that clarified the limitations associated with such assessments. Human blood was circulated in a closed-loop circuit via a pump operating at 4000 rpm at a flow rate of 5 L/min. Red blood cells flowing through a ridge area of the bearing were directly observed using a high-speed microscope. The hematocrit value in the ridge area was calculated using the mean corpuscular volume, the bearing gap, the cross-sectional area of a red blood cell, and the occupancy of red blood cells. The latter value was obtained from photographic images by dividing the number of pixels showing red blood cells in the evaluation area by the total number of pixels in this area. The plasma skimming efficiency was calculated as the extent to which the hematocrit of the working blood was reduced in the ridge area. For the hematocrit in the circuit from 0 to 40%, the plasma skimming efficiency was approximately 90%, meaning that the hematocrit in the ridge area became 10% as compared to that in the circuit. For a hematocrit of 20% and over, red blood cells almost completely occupied the ridge. Thus, a valid assessment of plasma skimming was only possible when the hematocrit was less than 20%.

Detection of thrombosis in a magnetically levitated blood pump by vibrational excitation of the impeller.

The use of contactless support technology for the impeller has led to an increase in the durability of ventricular assist devices (VADs), and these have been in clinical use worldwide. However, pump thrombosis and stroke are still issues to be solved. We have developed a method for detecting the thrombosis in a magnetically levitated blood pump without the need for additional sensors or other equipment. In the proposed method, a sinusoidal current is applied to the electromagnets used for the magnetic bearing, resulting in vibration of the impeller. The phase difference between the current and displacement of the impeller increases with pump thrombosis. First, we describe the principle by which the pump thrombosis is detected. Pump thrombosis reduces the narrowest fluid gap in the pump and this gives rise to a change in the phase difference. Second, we report on experiments in which we changed the narrowest fluid gap using oriented polypropylene tape and showed that decreasing the narrowest fluid gap resulted in an increase in phase difference. For these experiments, the measurements were repeated three times for each condition. Third, we examine the relationship between the pump thrombosis and the phase difference evaluated by observations of the underside of the impeller when operating the pump with porcine blood. Since light was unable to penetrate the blood layer, the erythrocytes were removed for this observation. Only one observation was made. The results showed the phase difference rapidly increased at the same moment when the pump thrombosis was observed. This implies the proposed method has the potential to detect the early stages of pump thrombosis. Finally, in vitro experiments to detect thrombosis when using whole porcine blood in the pump were conducted. The experiment was carried out five times. To intentionally form a thrombus inside the pump, the activated clotting time was controlled to be less than 200 s. In every case, the phase difference increased by more than one degree after tens of minutes. Then, the pump was disassembled and a small amount of pump thrombosis was observed. We conclude that real-time diagnosis of pump thrombosis may be realized by measuring the phase difference without the need for additional sensors.

Development of an Intelligent Ventricular Assist Device with a Function of Sensorless Thrombus Detection.

Thrombus is one of the major problems in ventricular assist devices (VADs). However, method for detecting thrombus in early stage has not been established yet. In this study, we propose an intelligent function that the VAD itself can detect thrombus automatically and alert it to medical staffs. In the proposed method, thrombus formation inside a blood pump is detected by monitoring blood viscosity. This viscosity measurement is performed by using magnetic levitation system for the impeller. Hence, it can be implemented without any additional sensors or mechanisms in principle. For verification of the method, at first, we visualized inside of the pump during thrombus formation with measuring blood viscosity by using erythrocytes removed porcine blood. The result showed that the viscosity of the blood increased as blood coagulation progressed. Then, we conducted in vitro principle verification experiments with three different whole porcine blood. In all experiments, the measured blood viscosity increased and small thrombus was observed inside the pump. From these results, we confirmed that the proposed method has a possibility to detect and predict the thrombus in early stage.

Red blood cells aggregability measurement of coagulating blood in extracorporeal circulation system with multiple-frequency electrical impedance spectroscopy.

Red blood cells (RBCs) aggregability AG of coagulating blood in extracorporeal circulation system has been investigated under the condition of pulsatile flow. Relaxation frequency fc from the multiple-frequency electrical impedance spectroscopy is utilized to obtain RBCs aggregability AG. Compared with other methods, the proposed multiple-frequency electrical impedance method is much easier to obtain non-invasive measurement with high speed and good penetrability performance in biology tissues. Experimental results show that, RBCs aggregability AG in coagulating blood falls down with the thrombus formation while that in non-coagulation blood almost keeps the same value, which has a great agreement with the activated clotting time (ACT) fibrinogen concertation (Fbg) tests. Modified Hanai formula is proposed to quantitatively analyze the influence of RBCs aggregation on multiple-frequency electrical impedance measurement. The reduction of RBCs aggregability AG is associated with blood coagulation reaction, which indicates the feasibility of the high speed, compact and cheap on-line thrombus measurement biosensors in extracorporeal circulation systems.

Determining the minimum number of protein-protein interactions required to support known protein complexes.

The prediction of protein complexes from protein-protein interactions (PPIs) is a well-studied problem in bioinformatics. However, the currently available PPI data is not enough to describe all known protein complexes. In this paper, we express the problem of determining the minimum number of (additional) required protein-protein interactions as a graph theoretic problem under the constraint that each complex constitutes a connected component in a PPI network. For this problem, we develop two computational methods: one is based on integer linear programming (ILPMinPPI) and the other one is based on an existing greedy-type approximation algorithm (GreedyMinPPI) originally developed in the context of communication and social networks. Since the former method is only applicable to datasets of small size, we apply the latter method to a combination of the CYC2008 protein complex dataset and each of eight PPI datasets (STRING, MINT, BioGRID, IntAct, DIP, BIND, WI-PHI, iRefIndex). The results show that the minimum number of additional required PPIs ranges from 51 (STRING) to 964 (BIND), and that even the four best PPI databases, STRING (51), BioGRID (67), WI-PHI (93) and iRefIndex (85), do not include enough PPIs to form all CYC2008 protein complexes. We also demonstrate that the proposed problem framework and our solutions can enhance the prediction accuracy of existing PPI prediction methods. ILPMinPPI can be freely downloaded from http://sunflower.kuicr.kyoto-u.ac.jp/~nakajima/.

Development of a real-time and quantitative thrombus sensor for an extracorporeal centrifugal blood pump by near-infrared light.

We developed an optical thrombus sensor for a monopivot extracorporeal centrifugal blood pump. In this study, we investigated its quantitative performance for thrombus detection in acute animal experiments of left ventricular assist using the pump on pathogen-free pigs. Optical fibers were set in the driver unit of the pump. The incident light at the near-infrared wavelength of 810 nm was aimed at the pivot bearing, and the resulting scattered light was guided to the optical fibers. The detected signal was analyzed to obtain the thrombus formation level. As a result, real-time and quantitative monitoring of the thrombus surface area on the pivot bearing was achieved with an accuracy of 3.6 ± 2.3 mm2. In addition, the sensing method using the near-infrared light was not influenced by changes in the oxygen saturation and the hematocrit. It is expected that the developed sensor will be useful for optimal anticoagulation management for long-term extracorporeal circulation therapies.

RocSampler: regularizing overlapping protein complexes in protein-protein interaction networks.

BACKGROUND: In recent years, protein-protein interaction (PPI) networks have been well recognized as important resources to elucidate various biological processes and cellular mechanisms. In this paper, we address the problem of predicting protein complexes from a PPI network. This problem has two difficulties. One is related to small complexes, which contains two or three components. It is relatively difficult to identify them due to their simpler internal structure, but unfortunately complexes of such sizes are dominant in major protein complex databases, such as CYC2008. Another difficulty is how to model overlaps between predicted complexes, that is, how to evaluate different predicted complexes sharing common proteins because CYC2008 and other databases include such protein complexes. Thus, it is critical how to model overlaps between predicted complexes to identify them simultaneously. RESULTS: In this paper, we propose a sampling-based protein complex prediction method, RocSampler (Regularizing Overlapping Complexes), which exploits, as part of the whole scoring function, a regularization term for the overlaps of predicted complexes and that for the distribution of sizes of predicted complexes. We have implemented RocSampler in MATLAB and its executable file for Windows is available at the site, http://imi.kyushu-u.ac.jp/~om/software/RocSampler/ . CONCLUSIONS: We have applied RocSampler to five yeast PPI networks and shown that it is superior to other existing methods. This implies that the design of scoring functions including regularization terms is an effective approach for protein complex prediction.

Optical Dynamic Analysis of Thrombus Inside a Centrifugal Blood Pump During Extracorporeal Mechanical Circulatory Support in a Porcine Model.

Complications due to pump thrombus remain the weak point of mechanical circulatory support (MCS), such as the use of a left ventricular assist device (LVAD) or extracorporeal membrane oxygenation, leading to poor outcomes. Hyperspectral imaging (HSI) is an effective imaging method using a hyperspectral (HS) camera, which comprises a spectrophotometer and a charge-coupled device camera to discriminate thrombus from whole blood. Animal experiments were conducted to analyze dynamic imaging of thrombus inside a prototype of a hydrodynamically levitated centrifugal blood pump using an HSI system. Six pigs were divided into a venous circulation group (n = 3) and an arterial circulation group (n = 3). Inflow and outflow cannulae were inserted into the jugular veins in the venous circulation group. The latter simulated an LVAD application. To create thrombogenic conditions, pump flow was maintained at 1 L/min without anticoagulation. An image of the bottom surface of the pump was captured by the HS camera every 4 nm over the wavelength range of 608-752 nm. Real-time dynamic images of the inside of the pump were displayed on the monitor. Appearance of an area displaying thrombus was detected within 24 h after the start of the circulation in every experiment. This imaging system also succeeded in determining the origins of pump thrombus: from inside the pump in two cases, and from outside in four cases. Two main possible sources of pump thrombus originating outside the pump were identified on autopsy: wedge thrombus around the inflow cannula; and string-like thrombus at the junction between the pump inlet and circuit tube. The results of this study from close observation of the changing appearance of pump thrombus may contribute to improvements in the safety of extracorporeal MCS.

Long-term durability test of axial-flow ventricular assist device under pulsatile flow.

A long-term durability test was conducted on a newly developed axial-flow ventricular assist device (VAD) with hydrodynamic bearings. The mock circulatory loop consisted of a diaphragm pump with a mechanical heart valve, a reservoir, a compliance tank, a resistance valve, and flow paths made of polymer or titanium. The VAD was installed behind the diaphragm pump. The blood analog fluid was a saline solution with added glycerin at a temperature of 37 °C. A pulsatile flow was introduced into the VAD over a range of flow rates to realize a positive flow rate and a positive pressure head at a given impeller rotational speed, yielding a flow rate of 5 L/min and a pressure of 100 mmHg. Pulsatile flow conditions were achieved with the diastolic and systolic flow rates of ~0 and 9.5 L/min, respectively, and an average flow rate of ~5 L/min at a pulse rate of 72 bpm. The VAD operation was judged by not only the rotational speed of the impeller, but also the diastolic, systolic, and average flow rates and the average pressure head of the VAD. The conditions of the mock circulatory loop, including the pulse rate of the diaphragm pump, the fluid temperature, and the fluid viscosity were maintained. Eight VADs were tested with testing periods of 2 years, during which they were continuously in operation. The VAD performance factors, including the power consumption and the vibration characteristics, were kept almost constant. The long-term durability of the developed VAD was successfully demonstrated.

Development of an Optical Detector of Thrombus Formation on the Pivot Bearing of a Rotary Blood Pump.

Continuous optical monitoring of thrombus formation in extracorporeal mechanical circulatory support (EMCS) devices will contribute to safe, long-term EMCS. A clinically applicable optical detector must be able to distinguish among the optical characteristics of oxygen saturation (SaO2 ), hematocrit (Hct), and thrombus formation. In vitro studies of spectral changes at wavelengths from 400 to 900 nm associated with SaO2 , Hct, and thrombus formed around the top pivot bearing of a Gyro C1E3 pump were conducted. Fresh porcine blood anticoagulated with sodium citrate was circulated in a mock circuit using the pump. The SaO2 , Hct, and anticoagulation activity were altered using an oxygenator, autologous plasma, and calcium chlorite injection, respectively. Light from a xenon lamp was guided by an incident fiber perpendicularly fixed on the top bearing. This light was scattered by blood pooled between the male and female pivots. The detection fiber was perpendicularly fixed against the incident fiber, and the side-scattered light was detected and guided to a spectrophotometer. As a result, light at two different wavelengths, 420 and 810 nm, was identified as suitable for thrombus detection because it was negligibly influenced by SaO2 and was able to detect the optical characteristics of fibrin. The light at these two wavelengths responded more quickly to thrombus formation than the inlet or outlet pressure, and flow rate change. The optical changes showed the changes in Hct around the top pivot bearing, which is caused by the reduction in density of fibrin-trapped red blood cells (RBCs) due to the RBCs being swept away by the surrounding blood flow. The proposed method was also able to detect fibrin production by extracting subtle differences in the optical characteristics between the Hct and thrombus formation.

Plasma Skimming in a Spiral Groove Bearing of a Centrifugal Blood Pump.

Plasma skimming is a phenomenon in which discharge hematocrit is lower than feed hematocrit in microvessels. Plasma skimming has been investigated at a bearing gap in a spiral groove bearing (SGB), as this has the potential to prevent hemolysis in the SGB of a blood pump. However, it is not clear whether plasma skimming occurs in a blood pump with the SGB, because the hematocrit has not been obtained. The purpose of this study is to verify plasma skimming in an SGB of a centrifugal blood pump by developing a hematocrit measurement method in an SGB. Erythrocyte observation using a high-speed microscope and a bearing gap measurement using a laser confocal displacement meter was performed five times. In these tests, bovine blood as a working fluid was diluted with autologous plasma to adjust the hematocrit to 1.0%. A resistor was adjusted to achieve a pressure head of 100 mm Hg and a flow rate of 5.0 L/min at a rotational speed of 2800 rpm. Hematocrit on the ridge region in the SGB was measured using an image analysis based on motion image of erythrocytes, mean corpuscular volume, the measured bearing gap, and a cross-sectional area of erythrocyte. Mean hematocrit on the ridge region in the SGB was linearly reduced from 0.97 to 0.07% with the decreasing mean bearing gap from 38 to 21 µm when the rotational speed was changed from 2250 to 3000 rpm. A maximum plasma skimming efficiency of 93% was obtained with a gap of 21 µm. In conclusion, we succeeded in measuring the hematocrit on the ridge region in the SGB of the blood pump. Hematocrit decreased on the ridge region in the SGB and plasma skimming occurred with a bearing gap of less than 30 µm in the hydrodynamically levitated centrifugal blood pump.