Circulatory Loop Research Articles

Simulating Radial Pressure Waveforms with a Mock Circulatory Flow Loop to Characterize Hemodynamic Monitoring Systems.

Mock circulatory loops (MCLs) can reproducibly generate physiologically relevant pressures and flows for cardiovascular device testing. These systems have been extensively used to characterize the performance of therapeutic cardiac devices, but historically MCLs have had limited use for assessing patient monitoring systems. Here, we adapted an MCL to include peripheral components and evaluated its utility for qualitative and quantitative benchtop testing of hemodynamic monitoring devices. An MCL was designed to simulate three physiological hemodynamic states: normovolemia, cardiogenic shock, and hyperdynamic circulation. The system was assessed for stability in pressure and flow values over time, repeatability, waveform morphology, and systemic-peripheral pressure relationships. For each condition, cardiac output was controlled to the nearest 0.2L/min, and flow rate and mean arterial pressure remained stable and repeatable over a 60-s period (n=5, standard deviation of±0.1L/min and±0.84mmHg, respectively). Transfer function analyses showed that the systemic-peripheral relationships could be adequately manipulated. The results from this MCL were comparable to those from other published MCLs and computational simulations. However, resolving current limitations of the system would further improve its utility. Three pulse contour analysis algorithms were applied to the pressure and flow data from the MCL to demonstrate the potential role of MCLs in characterizing hemodynamic monitoring systems. Overall, the development of robust analysis methods in conjunction with modified MCLs can expand device testing applications to hemodynamic monitoring systems. Properly validated MCLs can create a stable and reproducible environment for testing patient monitoring systems over their entire operating ranges prior to clinical use.

Intraventricular flow visualization in different heart failure stages with blood pump support in a mock circulatory loop

The intraventricular blood flow changed by blood pump flow dynamics may correlate with thrombosis and ventricular suction. The flow velocity, distribution of streamlines, vorticity, and standard deviation of velocity inside a left ventricle failing to different extents throughout the cardiac cycle when supported by an axial blood pump were measured by particle image velocimetry (PIV) in this study. The results show slower and static flow velocities existed in the central region of the left ventricle near the mitral valve and aortic valve and that were not sensitive to left ventricular (LV) failure degree or LV pressure. Strong vorticity located near the inner LV wall around the LV apex and the blood pump inlet was not sensitive to LV failure degree or LV pressure. Higher standard deviation of the blood velocity at the blood pump inlet decreased with increasing LV failure degree, whereas the standard deviation of the velocity near the atrium increased with increasing intraventricular pressure. The experimental results demonstrated that the risk of thrombosis inside the failing left ventricle is not related to heart failure degree. The "washout" performance of the strong vorticity near the inner LV wall could reduce the thrombotic potential inside the left ventricle and was not related to heart failure degree. The vorticity near the aortic valve was sensitive to LV failure degree but not to LV pressure. We concluded that the risk of blood damage caused by adverse flow inside the left ventricle decreased with increasing LV pressure.

Intra-aortic Balloon Pump Use With Extra Corporeal Membrane Oxygenation-A Mock Circulation Loop Study.

Venoarterial extracorporeal membrane oxygenation (ECMO) is used in cardiogenic shock refractory to inotropic support and intra-aortic balloon pump (IABP) support. Peripheral ECMO can lead to ventricular distention, and IABP can be used to mitigate these effects. The aim of this study was to quantify the effects of IABP concomitant with ECMO, under different simulated hemodynamic conditions in a mock circulatory loop. Different simulated states of isolated left ventricular (LV) failure and biventricular failure with graded LV failure severities were supported with ECMO and ECMO with IABP. The impact on left ventricular end-diastolic pressure (LVEDP), volume (LVEDV), coronary flow rate, and cerebral flow rate were evaluated. Left ventricular volumes and pressures increased from the heart failure states with the addition of ECMO. The IABP provided between 3% and 7% reductions in LVEDP and between 1% and 10% reductions in LVEDV. The addition of IABP had minimal effect on cerebral blood flow (0% to 7%), but the variable impact on coronary blood flow with increased diastolic coronary flow of 23% to 50%, but the reduction in mean coronary flow by up to 30%. The efficacy of the IABP was strongly related to ventricular contractility. This study demonstrates the need for careful IABP selection concomitant with ECMO.

Left atrial assist device for heart failure with preserved ejection fraction: initial results with torque control mode in diastolic heart failure model.

A novel pump, the left atrial assist device (LAAD), is a device specifically for the treatment of heart failure with preserved ejection fraction (HFpEF). The LAAD is a mixed-flow pump that is implanted in the mitral position and delivers blood from the left atrium to the left ventricle. During the development process, we aimed to explore whether device activation in torque control (TC) mode would improve the function of the LAAD. The TC mode causes adjustment of the pump speed automatically during each cardiac cycle in order to maintain a specified torque. In this study, we tested four different TC settings (TC modes 0.9, 1.0, 1.25, and 1.5) using an in vitro mock circulatory loop. Mild, moderate, and severe diastolic heart failure (DHF) conditions, as well as normal heart condition, were simulated with the four TC modes. Also, we evaluated the LAAD in vivo with three calves. The LAAD was implanted at the mitral position with four TC settings (TC modes 0.9, 1.0, 1.1, 1.2). With LAAD support, the in vitro cardiac output and aortic pressure recovered to normal heart levels at TC 1.25 and 1.5 even under severe DHF conditions with little pump regurgitation. The TC mode tested in vivo with three calves, and it also showed favorable result without elevating the left ventricular end-diastolic pressure. These initial in vitro and in vivo results suggest that the TC mode could be potentially effective, and the LAAD could be a treatment option for HFpEF patients.

Experimental investigation of the influence of the hydraulic performance of an axial blood pump on intraventricular blood flow.

Blood flow inside the left ventricle (LV) is a concern for blood pump use and contributes to ventricle suction and thromboembolic events. However, few studies have examined blood flow inside the LV after a blood pump was implanted. In this study, in vitro experiments were conducted to emulate the intraventricular blood flow, such as blood flow velocity, the distribution of streamlines, vorticity and the standard deviation of velocity inside the LV during axial blood pump support. A silicone LV reconstructed from computerized tomography (CT) data of a heart failure patient was incorporated into a mock circulatory loop (MCL) to simulate human systemic circulation. Then, the blood flow inside the ventricle was examined by particle image velocimetry (PIV) equipment. The results showed that the operating conditions of the axial blood pump influenced flow patterns within the LV and areas of potential blood stasis, and the intraventricular swirling flow was altered with blood pump support. The presence of vorticity in the LV from the thoracic aorta to the heart apex can provide thorough washing of the LV cavity. The gradually extending stasis region in the central LV with increasing blood pump support is necessary to reduce the thrombosis potential in the LV.

Understanding the Impact of Hypertension on Left Ventricular Assist Device Pump Function and Thrombotic Risk.

Understanding the Impact of Hypertension on Left Ventricular Assist Device Pump Function and Thrombotic Risk.

Using the Sinoatrial Node to Induce Pulsatility in Mechanical Circulatory Support Devices

<h3>Purpose</h3> Mechanical Circulatory Support (MCS) devices such as ventricular assist devices (VADs) are increasingly important in managing patients with end-stage heart failure. Current generation VADs, such as the HVAD operate on a continuous flow basis. Many authors have identified the lack of pulsatility as a limitation. We tested the feasibility of using a signal from ex-vivo tissue of rabbit sinoatrial node (SAN) to induce pulsatility in an HVAD as well as the BiVACOR total artificial heart through synchronous speed variation. <h3>Methods</h3> Seven different rabbits had SAN tissue extracted, placed in a tissue bath and superfused with Krebs-Ringer solution. An extracellular fine metal electrode was placed into the tissue preparation for activity capture. The rate of spontaneous SAN activity was modulated by changing the temperature of the superfusing solution. Electrical activity was captured and identified using a data acquisition system and custom-made software. This was used to trigger a stepwise speed change in an HVAD as well as the BiVACOR running in a mock circulatory loop. Signal capture was tested across a range of heart rates. <h3>Results</h3> Electrogram signals were successfully recorded for all tissue extracts. To simulate physiological settings, we implemented a 100ms delay between capture and effect, as well as a speed change duration of 30% per cycle (obtained from beat-to-beat variation). HVAD motor speed was successfully increased from 2500RPM to 2800RPM in synchronicity with the firing of the SAN. We were also able to achieve a speed reduction from 2500RPM to 2000RPM in synchronicity with the firing of the SAN. The BIVACOR was similarly able to undergo motor speed increase and decrease in synchrony with the SAN at the lower heart rate setting. <h3>Conclusion</h3> We successfully captured electrical activity from the SAN, then relayed it to both an HVAD and the BiVACOR controller, in doing so we were able to induce pulsatility through speed variation in synchrony with SAN activity. This has the potential to change MCS haemodynamics.

Aortic arch aneurysm repair – Unsteady hemodynamics and perfusion at different heart rates

The aortic arch aneurysm is a complex disease that requires branching of one or more aortic arch vessels and can be fatal if left untreated. In this in vitro study, we examine the effect of the treatment approach on the unsteady hemodynamics and blood perfusion to the upper vessel's in models of an aortic arch aneurysm, and of the three common repair approaches: open-chest surgical repair, chimney, and hybrid approach. A particle image velocimetry method was used to quantify the unsteady hemodynamics in the four models simulated in a mock circulatory loop, to evaluate unsteady hemodynamic parameters and measure perfusion to the brain and the upper body.According to the findings, in terms of perfusion to the brain and upper body, the surgery model has the highest flow rate comparing to the other models in most heart-rate conditions. It also shows oscillatory parameters in the upper vessels which in normal arteries are correlated with a better arterial function. Between the two endovascular procedures, the hybrid model exhibits slightly better hemodynamic characteristics than the chimney model, with lower shear stresses and more oscillatory flow and WSS in the upper vessels. The hybrid model had lower perfusion flow rates to upper vessels during rest conditions (90BPM). However, unlike the other models, perfusion in the hybrid model increased with heart rate, thus at 135 BPM, it results in flow rate to upper vessels similar to that of the chimney model. The results of this study may shed light on future endograft' design and placement techniques.

Altered hemodynamics by 4D flow cardiovascular magnetic resonance predict exercise intolerance in repaired coarctation of the aorta: an in vitro study

BackgroundCoarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair. Altered flow patterns have been identified due to abnormal aortic arch geometry. Our previous work demonstrated aorta size mismatch to be associated with exercise intolerance in this population. In this study, we studied aortic flow patterns during simulations of exercise in repaired CoA using 4D flow cardiovascular magnetic resonance (CMR) using aortic replicas connected to an in vitro flow pump and correlated findings with exercise stress test results to identify biomarkers of exercise intolerance.MethodsPatients with CoA repair were retrospectively analyzed after CMR and exercise stress test. Each aorta was manually segmented and 3D printed. Pressure gradient measurements from ascending aorta (AAo) to descending aorta (DAo) and 4D flow CMR were performed during simulations of rest and exercise using a mock circulatory flow loop. Changes in wall shear stress (WSS) and secondary flow formation (vorticity and helicity) from rest to exercise were quantified, as well as estimated DAo Reynolds number. Parameters were correlated with percent predicted peak oxygen consumption (VO2max) and aorta size mismatch (DAAo/DDAo).ResultsFifteen patients were identified (VO2max 47 to 126% predicted). Pressure gradient did not correlate with VO2max at rest or exercise. VO2max correlated positively with the change in peak vorticity (R = 0.55, p = 0.03), peak helicity (R = 0.54, p = 0.04), peak WSS in the AAo (R = 0.68, p = 0.005) and negatively with peak WSS in the DAo (R = − 0.57, p = 0.03) from rest to exercise. DAAo/DDAo correlated strongly with change in vorticity (R = − 0.38, p = 0.01), helicity (R = − 0.66, p = 0.007), and WSS in the AAo (R = − 0.73, p = 0.002) and DAo (R = 0.58, p = 0.02). Estimated DAo Reynolds number negatively correlated with VO2max for exercise (R = − 0.59, p = 0.02), but not rest (R = − 0.28, p = 0.31). Visualization of streamline patterns demonstrated more secondary flow formation in aortic arches with better exercise capacity, larger DAo, and lower Reynolds number.ConclusionsThere are important associations between secondary flow characteristics and exercise capacity in repaired CoA that are not captured by traditional pressure gradient, likely due to increased turbulence and inefficient flow. These 4D flow CMR parameters are a target of investigation to identify optimal aortic arch geometry and improve long term clinical outcomes after CoA repair.

Object‐Oriented Lumped‐Parameter Modeling of the Cardiovascular System for Physiological and Pathophysiological Conditions

AbstractIn this work, a lumped‐parameter Windkessel model of the cardiovascular system that simulates biomechanical parameters of the human physiology is presented. The object‐oriented platform provided by the MATLAB‐based modeling environment SIMSCAPE is employed to compute blood pressures and flows in each heart chamber and at various sites of the vascular tree. The hydraulic domain allows the determination of cardiovascular hemodynamics intuitively from geometrical and mechanical properties of the system, while custom elements model the pumping action of the heart and the effects of respiration on blood flow. The model is validated by comparing predicted hemodynamics with normal physiology during both systole and diastole, demonstrating that changes in arterial pressures with breathing are consistent with reported physiological effects of cardiorespiratory coupling. The capabilities of this platform are explored through two exemplary case studies: i) pressure‐overload heart failure due to aortic constriction, validated in vitro and via finite element analysis, and ii) single‐ventricle Fontan physiology, validated in vitro and compared with the clinical literature. This platform provides a practical tool for the calculation of cardiovascular hemodynamics from hydraulic parameters, enabling the intuitive creation of in silico representations of complex circulatory loops, the planning and optimization of medical interventions, and the prediction of clinically relevant patient‐specific hemodynamics.

Building the complex architectures of vascular networks: Where to branch, where to connect and where to remodel?

The cardiovascular system is the first organ to become functional during vertebrate embryogenesis and is responsible for the distribution of oxygen and nutrients to all cells of the body. The cardiovascular system constitutes a circulatory loop in which blood flows from the heart through arteries into the microvasculature and back through veins to the heart. The vasculature is characterized by the heterogeneity of blood vessels with respect to size, cellular architecture and function, including both larger vessels that are found at defined positions within the body and smaller vessels or vascular beds that are organized in a less stereotyped manner. Recent studies have shed light on how the vascular tree is formed and how the interconnection of all branches is elaborated and maintained. In contrast to many other branched organs such as the lung or the kidney, vessel connection (also called anastomosis) is a key process underlying the formation of vascular networks; each outgrowing angiogenic sprout must anastomose in order to allow blood flow in the newly formed vessel segment. It turns out that during this "sprouting and anastomosis" process, too many vessels are generated, and that blood flow is subsequently optimized through the removal (pruning) of low flow segments. Here, we reflect on the cellular and molecular mechanisms involved in forming the complex architecture of the vasculature through sprouting, anastomosis and pruning, and raise some questions that remain to be addressed in future studies.

Left atrial assist device function at various heart rates using a mock circulation loop.

We are developing a new left atrial assist device (LAAD) for patients who have heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the hemodynamic effects of the LAAD under both normal heart conditions and various diastolic heart failure (DHF) conditions using a mock circulatory loop. A continuous-flow pump that simulates LAAD, was placed between the left atrial (LA) reservoir and a pneumatic ventricle that simulated a native left ventricle on a pulsatile mock loop. Normal heart (NH) and mild, moderate, and severe DHF conditions were simulated by adjusting the diastolic drive pressures of the pneumatic ventricle. With the LAAD running at 3200 rpm, data were collected at 60, 80, and 120 bpm of the pneumatic ventricle. Cardiac output (CO), mean aortic pressure (AoP), and mean LA pressure (LAP) were compared to evaluate the LAAD performance. With LAAD support, the CO and AoP rose to a sufficient level at all heart rates and DHF conditions (CO; 3.4-3.8 L/min, AoP; 90-105 mm Hg). Each difference in the CO and the AoP among various heart rates was minuscule compared with non-pump support. The LAP decreased from 21-23 to 17-19 mm Hg in all DHF conditions (difference not significant). Furthermore, hemodynamic parameters improved for all DHF conditions, independent of heart rate. The LAAD can provide adequate flow to maintain the circulation status at various heart rates in an in vitro mock circulatory loop.

In vitro calcification studies on bioprosthetic and decellularized heart valves under quasi-physiological flow conditions

The lifespan of biological heart valve prostheses available in the market is limited due to structural alterations caused by calcium phosphate deposits formed from blood plasma in contact with the tissues. The objective of this work is to present a comparative methodology for the investigation of the formation of calcium phosphate deposits on bioprosthetic and tissue-engineered scaffolds in vitro and the influence of mechanical forces on tissue mineralization. Based on earlier investigations on biological mineralization at constant supersaturation, a circulatory loop simulating dynamic blood flow and physiological pressure conditions was developed. The system was appropriately adapted to evaluate the calcification potential of decellularized (DCV) and glutaraldehyde-fixed (GAV) porcine aortic valves. Results indicated that DCV calcified at higher, statistically nonsignificant, rates in comparison with GAV. This difference was attributed to the tissue surface modifications and cell debris leftovers from the decellularization process. Morphological analysis of the solids deposited after 20 h by scanning electron microscopy in combination with chemical microanalysis electron-dispersive spectroscopy identified the solid formed as octacalcium phosphate (Ca8(PO4)6H2·5H2O, OCP). OCP crystallites were preferentially deposited in high mechanical stress areas of the test tissues. Moreover, GAV tissues developed a significant transvalvular pressure gradient increase past 36 h with a calcium deposition distribution similar to the one found in explanted prostheses. In conclusion, the presented in vitro circulatory model serves as a valuable prescreening methodology for the investigation of the calcification process of bioprosthetic and tissue-engineered valves under physiological mechanical load.

Characterization of a pulsatile rotary total artificial heart.

This article describes the properties and performance of a rotary total artificial heart (TAH) that produces inherently pulsatile flow. The hydraulic performance of the TAH was characterized using a mock circulatory loop to simulate four physiologically relevant conditions: baseline flow, increased flow, systemic hypertension, and pulmonary hypertension. The pump has a variable shuttle rate (beats per minute), percentage dwell time, and angular velocity on either side (revolutions per minute), which allows for full control of the flow rate and pulsatility over a range of healthy and pathologic pressures and flow rates. The end-to-end length and displacement volume of the TAH are 9.8cm and 130mL, respectively, allowing it to fit in smaller chest cavities including those of smaller adults and juvenile humans.

In-vitro particle image velocimetry assessment of the endovascular haemodynamic features distal of stent-grafts that are associated with development of limb occlusion

ABSTRACT Aneurysms are common vascular diseases which affect normal haemodynamics in the aorta. Endovascular aortic repair (EVAR) using stent-grafts is a common treatment that excludes the aneurysm from the circulation, preventing further growth and eventual rupture. However, complications such as endoleak, dislocation or limb occlusion have been reported after EVAR. This study hypothesized that the compliance mismatch between the graft and parent artery causes haemodynamic disturbances at the distal edge of the graft. Therefore, the potential for the graft to cause limb occlusion was assessed. A compliant phantom was fabricated. A circulatory loop was developed to run the fluid and generate a physiological flow waveform. Particle Image Velocimetry was utilised to capture fluid dynamics in the replica. The result showed a low velocity region at the graft trailing edge wall. The low velocity boundary layer thickness decreased downstream of the graft. A flow recirculation was initiated and increased in size during the mid-acceleration at the low velocity region. Shear stresses fluctuated at the trailing edge of the graft which is a risk factor for intimal thickening followed by graft or limb occlusion. It was concluded that this haemodynamic behaviour was due to the graft and parent artery compliance mismatch.

Aorta size mismatch predicts decreased exercise capacity in patients with successfully repaired coarctation of the aorta

ObjectiveCoarctation of the aorta (CoA) is associated with decreased exercise capacity despite successful repair with no residual stenosis; however, the hemodynamic mechanism remains unknown. This study aims to correlate aortic arch geometry with exercise capacity in patients with successfully repaired CoA and explain hemodynamic changes using 3-dimensional–printed aorta models in a mock circulatory flow loop. MethodsA retrospective chart review identified patients with CoA repair who had cardiac magnetic resonance imaging and an exercise stress test. Measurements included aorta diameters, arch height to diameter ratio, left ventricular function, and percent descending aorta (%DAo) flow. Each aorta was printed 3-dimensionally for the flow loop. Flow and pressure were measured at the ascending aorta (AAo) and DAo during simulated rest and exercise. Measurements were correlated with percent predicted peak oxygen consumption (VO2 max). ResultsFifteen patients (mean age 26.8 ± 8.6 years) had a VO2 max between 47% and 126% predicted (mean 92 ± 20%) with normal left ventricular function. DAo diameter and %DAo flow positively correlated with VO2 (P = .007 and P = .04, respectively). AAo to DAo diameter ratio (DAAo/DDAo) negatively correlated with VO2 (P < .001). From flow loop simulations, the ratio of %DAo flow in exercise to rest negatively correlated with VO2 (P = .02) and positively correlated with DAAo/DDAo (P < .01). ConclusionsThis study suggests aorta size mismatch (DAAo/DDAo) is a novel, clinically important measurement predicting exercise capacity in patients with successful CoA repair, likely due to increased resistance and altered flow distribution. Aorta size mismatch and %DAo flow are targets for further clinical evaluation in repaired CoA.

A 3-dimensional-printed left ventricle model incorporated into a mock circulatory loop to investigate hemodynamics inside a severely failing ventricle supported by a blood pump.

Intraventricular blood stasis is a design consideration for continuous flow blood pumps and might contribute to adverse events such as thrombosis and ventricular suction. However, the blood flow inside left ventricles (LVs) supported by blood pumps is still unclear. In vitro experiments were conducted to imitate how the hydraulic performance of an axial blood pump affects the intraventricular blood flow of a severe heart failure patient, such as velocity distribution, vorticity, and standard deviation of velocity. In this study, a silicone model of the LV was constructed from the computed tomography data of one patient with heart failure and was 3D printed. Then, intraventricular flow was visualized by particle image velocimetry equipment within a mock circulation loop. The results showed that the axial blood pump suctions most of the blood in a severely failing LV, there was an altered flow status within the LV, and blood stasis appeared in the central region of the LV. Some blood may be suctioned from the aortic valve to the blood pump because the patient's native heart was severely failing. Blood stasis at the LV center may cause thrombosis in the LV. The vortex flow near the inner wall of the LV can thoroughly wash the left ventricular cavity.

A Combined In Vivo, In Vitro, In Silico Approach for Patient-Specific Haemodynamic Studies of Aortic Dissection

The optimal treatment of Type-B aortic dissection (AD) is still a subject of debate, with up to 50% of the cases developing late-term complications requiring invasive intervention. A better understanding of the patient-specific haemodynamic features of AD can provide useful insights on disease progression and support clinical management. In this work, a novel in vitro and in silico framework to perform personalised studies of AD, informed by non-invasive clinical data, is presented. A Type-B AD was investigated in silico using computational fluid dynamics (CFD) and in vitro by means of a state-of-the-art mock circulatory loop and particle image velocimetry (PIV). Both models not only reproduced the anatomical features of the patient, but also imposed physiologically-accurate and personalised boundary conditions. Experimental flow rate and pressure waveforms, as well as detailed velocity fields acquired via PIV, are extensively compared against numerical predictions at different locations in the aorta, showing excellent agreement. This work demonstrates how experimental and numerical tools can be developed in synergy to accurately reproduce patient-specific AD blood flow. The combined platform presented herein constitutes a powerful tool for advanced haemodynamic studies for a range of vascular conditions, allowing not only the validation of CFD models, but also clinical decision support, surgical planning as well as medical device innovation.

The Effects of Preserving Mitral Valve Function on a Left Atrial Assist Device: An In Vitro Mock Circulation Loop Study.

We are developing a left atrial assist device (LAAD) to pump blood from the left atrium to the left ventricle for patients who have heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the hemodynamics with the LAAD implanted at two different levels: the mitral valve (MV) level, after removing the MV; and the supravalvular level, preserving MV function conditions using an in vitro mock circulatory loop. Normal heart and mild, moderate, and severe diastolic heart failure conditions were simulated, and the LAAD was set at three different speeds. Without the LAAD support, cardiac output (CO) decreased from 3.7 to 1.1 L/min, aortic pressure (AoP) decreased from 100 to 33 mm Hg, and left atrial pressure (LAP) increased from 16 to 23 mm Hg as the diastolic function became impaired. With high pump support after removing the MV, CO and AoP readings were comparable with those for preserved MV function (CO reached 3.9-4.1 L/min, AoP reached more than 110 mm Hg, and LAP dropped to 16-17 mm Hg under both conditions at high pump speeds). In the mock circulatory loop, our LAAD appeared to have sufficient ability to maintain the hemodynamic status at both positions.

Isomer separation enabled by a micro circulatory gas chromatography system.

Isomers, holding similar chemical and physical properties, are difficult to separate especially by utilizing a microfabricated gas chromatography system due to limited column lengths mainly imposed by low-pressure (<20 kPa) micropump capability. In this paper, we demonstrated the separation of a pair of structural isomers, isopentane and pentane, in a micro-scale gas chromatography system with a circulatory loop of two 25-cm micro open tubular columns, while operating under a minimal pressure requirement of <10 kPa. The developed micro circulatory gas chromatography (MCGC) system achieved an effective column length of 12.5 meters by circulating the isomer gases for 25 cycles, the longest micro open tubular column length ever reported by any microfabricated GC systems yet.