This paper presents the design, fabrication, and experimental validation of a novel low-cost implantable pump for the treatment of refractory ascites (RA) based on local magnetic actuation (LMA). A reciprocating positive displacement pump displaces liquid unidirectionally through magnetic coupling with a magnetic controller placed on the outside of the patient's body. The proposed solution is intuitive to use given an alignment algorithm that exploits externally placed magnetic field sensors (MFS). The implantable device has a catheter-like shape, is electronic free (no on-board battery), has low fabrication cost (<8 USD), and is able to generate a flow-rate of 3.65 L/h while effectively pumping fluids with various viscosity (1–5.5 cP). RA is commonly treated via costly paracentesis or invasive surgical placement of a transjugular portosystemic shunt (TIPS). The proposed solution can be implanted with minimally invasive techniques and can be used on a daily basis to drain a set amount of liquid, without requiring recurrent hospital visits.

Assessing hemodynamics in vasculature is important for the development of cardiovascular diagnostic parameters and evaluation of medical devices. Benchtop experiments are a safe and comprehensive preclinical method for testing new diagnostic endpoints and devices within a controlled environment. Recent advances in three-dimensional (3D) printing have enhanced benchtop tests by allowing generation of patient-specific and pathophysiologic conditions. We used 3D printing, coupled with image processing and computer-aided design (CAD), to develop a patient-specific vascular test device from clinical data. The proximal pulmonary artery (PA) tree including the main, left, and right pulmonary arteries, with a stenosis within the left PA was selected as a representative anatomy for developing the vascular test device. Three test devices representing clinically relevant stenosis severities, 90%, 80%, and 70% area stenosis, were evaluated at different cardiac outputs (COs). A mock circulatory loop (MCL) generating pathophysiologic pulmonary pressure and flow was used to evaluate the hemodynamics within the devices. The dimensionless pressure drop–velocity ratio characteristic curves for the three stenosis severities were obtained. At a fixed CO, the dimensionless pressure drop increased nonlinearly with an increase in (a) the velocity ratio for a fixed stenosis severity and (b) the stenosis severity at a specific velocity ratio. The dimensionless pressure drop observed in vivo was similar (within 1%) to that measured in moderate area stenosis of 70% because both flows were viscous dominated. The hemodynamics of the 3D printed test device can be used for evaluating diagnostic endpoints and medical devices in a preclinical setting under realistic conditions.

Patients treated by current ventricular assist devices (VADs) suffer from various post implantation complications including gastrointestinal bleeding and arteriovenous malformation. These issues are related to intrinsically mismatch of generated flow by VADs and the physiological flow. In addition, the common primary drawback of available VADs is excessive surgical dissection during implantation, which limits these devices to less morbid patients. We investigated an alternative soft VAD (SVAD) system that generates physiological flow, and designed to be implanted using minimally invasive surgery by leveraging soft materials. A soft VAD (which is an application of intraventricular balloon pump) is developed by utilizing a polyurethane balloon, which generates pulsatile flow by displacing volume within the left ventricle during its inflation and deflation phases. Our results show that the SVAD system generates an average ejection fraction of 50.18 ± 1.52% (n = 6 ± SD) in explanted porcine hearts. Since the SVAD is implanted via the apex of the heart, only a minithoracotomy should be required for implantation. Our results suggest that the SVAD system has the performance characteristics that could potentially make it useful for patients in acute and/or chronic heart failure, thus serving as a bridge-to-transplantation or bridge-to-recovery.

Mechanical circulatory support (MCS) options are limited for patients with dysfunctional single ventricle physiology. To address this unmet clinical need, we are developing an axial-flow blood pump to provide mechanical assistance to the cavopulmonary circulation. In this study, we investigate the use of high-resolution cardiac magnetic resonance imaging (MRI) to visualize the complex fluid flow conditions of mechanical circulatory assist in two patient-specific Fontan anatomies. A three-bladed axial-flow impeller coupled to a supportive cage with a four-bladed diffuser was positioned in the inferior vena cava (IVC) of each Fontan anatomy. Cardiac magnetic resonance (CMR) imaging and power efficiency studies were conducted at physiologic relevant parameters with cardiac outputs of 2, 3, and 4 L/min with impeller rotational speeds of 2000 and 4000 rpm. The axial-flow impeller was able to generate improved flow in the total cavopulmonary connection (TCPC). The higher rotational speed was able to redistribute flow in the TCPC anastomosis aiding in removing stagnant blood. No retrograde flow was observed or measured in the superior vena cava (SVC). As an extension of the CMR data, a scalar stress analysis was performed on both models and found a maximum scalar stress of approximately 42 Pa for both patient anatomies. The power efficiency experiments demonstrated a maximum energy gain of 8.6 mW for TCPC Anatomy 1 and 12.58 mW for TCPC Anatomy 2 for a flow rate of 4 L/min and at 4000 rpm. These findings support the continued development of axial blood pumps for mechanical cavopulmonary assist.

Efficient detection of pathogens is essential for the development of a reliable point-of-care diagnostic device. Magnetophoretic separation, a technique used in microfluidic platforms, utilizes magnetic microbeads (mMBs) coated with specific antigens to bind and remove targeted biomolecules using an external magnetic field. In order to assure reliability and accuracy in the device, the efficient capture of these mMBs is extremely important. The aim of this study was to analyze the effect of an electroosmotic flow (EOF) switching device on the capture efficiency (CE) of mMBs in a microfluidic device and demonstrate viability of bacteria capture. This analysis was performed at microbead concentrations of 2 × 10 6 beads/mL and 4 × 10 6 beads/mL, EOF voltages of 650 V and 750 V, and under constant flow and switching flow protocols. Images were taken using an inverted fluorescent microscope and the pixel count was analyzed to determine to fluorescent intensity. A capture zone was used to distinguish which beads were captured versus uncaptured. Under the steady-state flow protocol, CE was determined to range from 31% to 42%, while the switching flow protocol exhibited a CE of 71–85%. The relative percentage increase due to the utilization of the switching protocol was determined to be around two times the CE, with p < 0.05 for all cases. Initial testing using bacteria-bead complexes was also performed in which these complexes were captured under the constant flow protocol to create a calibration curve based on fluorescent pixel count. The calibration curve was linear on a log-log plot, with R 2 -value of 0.96. The significant increase in CE highlights the effectiveness of flow switching for magnetophoretic separation in microfluidic devices and prove its viability in bacterial analysis.

Detection and capture of circulating tumor cells (CTCs) with microfluidic chips hold significance in cancer prognosis, diagnosis, and anti-cancer treatment. The counting of CTCs provides potential tools to evaluate cancer stages as well as treatment progress. However, facing the challenge of rareness in blood, the precise enumeration of CTCs is challenging. In the present research, we designed an inertial-deformability hybrid microfluidic chip using a long spiral channel with trapezoid-circular pillars and a capture zone. To clinically validate the device, the microfluidic chip has been tested for the whole blood and lysed blood with a small number of CTCs (colorectal and nonsmall-cell lung cancer) spiked in. The capture efficiency reaches over 90% for three types of cancer cell lines at the flow rate of 1.5 mL/h. Following numerical modeling was conducted to explain the working principle and working condition (Reynolds number below 10 and Dean number around 1). This design extended the effective capture length, improved the capture efficiency, and made the CTC enumeration much easier. We believe that this hybrid chip is promising clinically in the CTCs enumeration, evaluation of cancer therapy, and pharmacological responses.

Pulsatile waves of blood pressure and flow are continuously augmented by the resistance, compliance, and inertance properties of the vasculature, resulting in unique wave characteristics at distinct anatomical locations. Hemodynamically generated loads, transduced as physical signals into resident vascular cells, are crucial to the maintenance and preservation of a healthy vascular physiology; thus, failure to recreate biomimetic loading in vitro can lead to pathological gene expression and aberrant remodeling. As a generalized approach to improve native and engineered blood vessels, we have designed, built, and tested a pulsatile perfusion bioreactor based on biomimetic impedances and a novel five-element electrohydraulic analog. Here, the elements of an incubator-based culture system were formulaically designed to match the vascular impedance of a brachial artery by incorporating both the inherent (systemic) and added elements of the physical system into the theoretical approach. Freshly harvested porcine saphenous veins were perfused within a physiological culture chamber for 6 h and the relative expression of seven known mechanically sensitive remodeling genes analyzed using the quantitative polymerase chain reaction (qPCR) method. Of these, we found plasminogen activator inhibitor-1 (SERPINE1) and fibronectin-1 (FN1) to be highly sensitive to differences between arterial- and venous-like culture conditions. The analytical approach and biological confirmation provide a framework toward the general design of long-term hemodynamic-mimetic vascular culture systems.

Dielectrophoresis (DEP) can be an effective tool to show the physiological change of bacterial cells. The behavior of bacterial cells under an electric field is complicated due to the combined effects of electrokinetic phenomena. This paper presents the study of the electrokinetic behavior of heat-treated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cells for a cell counting method. Through numerical and experimental study, heat-treated BCG cells are compared with control BCG cells. At various frequencies with the medium conductivity of 0.07 S/m, the equilibrium positions of both control- and heat-treated cells are analyzed in the combined fields of DEP and AC electroosmosis (ACEO). As DEP changes from negative to positive in electroosmotic flow, the equilibrium position of cells is bifurcated from the upper center between two electrodes onto the edges of both electrodes. It was found that the cells floating on electrodes should not be counted as attracted cells because the floating was resulted from the combined effect of the negative DEP and ACEO. According to the analysis, an optimum frequency is proposed to differentiate control cells from heat-treated cells using a cell counting method. The presented study will offer physical insight for the cell counting to differentiate live and dead Mycobacterium bovis BCG cells treated with heat and drugs.

A fully implantable circulatory assistance device without external connection and lifetime energy supply can eliminate a significant source of morbidity and mortality for patients. Here, we present and discuss concept and preliminary results of an original project for a not-motorized, fully implantable circulatory assistance device. The not-motorized implantable circulatory assistance device (NICA) has been tested into a cardiac simulator that was conceived according to the FDA and ISO standards. The instrumentation incorporated to the cardiac simulator includes probes for the aortic pressure (AoP) proximally to the device, a temperature control system, and one electromagnetic flowmeter to acquire the flow rate (AoF) proximally to the device. A control software allows to modulate the drive parameters such as velocity, acceleration, number of revolutions, the stroke volume, and the heart rate. Experiments have been performed with three different circuit resistances: 2100 dyn s/cm 5 , 1400, and 700. The AoF increased in the assisted cycles: 71% at 2100 dyn s/cm 5 , 67% at 1400 dyn s/cm 5 , and 25% at 700 dyn s/cm 5 . NICA performs a partial but significant support of AoF without energy supply. The improvement of AoF increases with the increasing of vascular resistances. The feedback received by this preliminary bench experiment acted as a preliminary proof of concept of this new device.

This presents the influence of gamma irradiation on Pharmacopeia specifications, mechanical and flow parameters of polypropylene (PP) syringes. There has been significant progress in the terminal sterilization of single-use, disposable medical devices with gamma radiation sterilization due to the growing awareness of toxic residues during the ethylene oxide (EtO) sterilization. PP is a widely used polymer for the production of syringes because of its excellent mechanical and thermal properties and has expanded continuously over the last decade. Although 25 kGy was generally recommended for the gamma radiation sterilization of medical products, this radiation dose is high enough to produce substantial damage. Electron spin resonance (ESR) characteristics of irradiated syringes were also studied at normal (25 °C, 60% relative humidity) and accelerated (40 °C, 75% relative humidity) stability test conditions. It was found that the chemical and radiolytic changes and sterility assurance levels (SAL) after gamma radiation sterilization were different in PP syringes. It was shown that for two commercial syringes, E1 and E3, a SAL of 10 −4 could be attained with only 10 kGy, with there being less detrimental radiation effects on E1. The differences in the radiosensitivity of the propylene syringes could be due to the different formulations and manufacturing processes. The results indicated that a commercial syringe, identified as E1 could be safely sterilized with gamma irradiation as the radicals decay over a period of days under normal conditions and quenched much faster under stability conditions. Furthermore, ESR technique could be used successfully in monitoring the radiosterilization of this material. Additionally, the confirmation and validation of the SAL doses which are below 25 kGy, will decrease the time and cost of the sterilization with less damaging effects of ionizing irradiation.

Retransfusion of a patient's own shed blood during cardiac surgery is attractive since it reduces the need for allogeneic transfusion, minimizes cost, and decreases transfusion related morbidity. Evidence suggests that lipid micro-emboli associated with the retransfusion of the shed blood are the predominant causes of the neurocognitive disorders. We have developed a novel acoustophoretic filtration system that can remove lipids from blood at clinically relevant flow rates. Unlike other acoustophoretic separation systems, this ultrasound technology works at the macroscale, and is therefore able to process larger flow rates than typical micro-electromechanical system (MEMS) scale acoustophoretic separation devices. In this work, we have first demonstrated the systematic design of the acoustic device and its optimization, followed by examining the feasibility of the device to filter lipids from the system. Then, we demonstrate the effects of the acoustic waves on the shed blood; examining hemolysis using both haptoglobin formation and lactate dehydrogenase release, as well as the potential of platelet aggregation or inflammatory cascade activation. Finally, in a porcine surgical model, we determined the potential viability of acoustic trapping as a blood filtration technology, as the animal responded to redelivered blood by increasing both systemic and mean arterial blood pressure.

The multiphotodiode array (MPA) is a novel transmission photoplethysmography (PPG) sensor to measure pulse wave velocity (PWV) in the finger. To validate the MPA, a setup was built to generate a red laser dot traveling over the MPA with known and constant scanning velocities. These scanning velocities were chosen to include speeds at least twice as high as those found in the normal range of PWV in healthy populations and were set at 12.9, 25.8, 36, or 46.7 m/s. The aim of this study was to verify the functionality of the MPA: performing local noninvasive PWV measurements. To illustrate the applicability of the MPA in clinical practice, an in vivo pilot study was conducted using the flow-mediated dilation (FMD) technique. The in vitro accuracy of the MPA was ±0.2%, 0.3%, 0.5%, and 0.6% at the applied scanning velocities. The MPA can measure PWVs with a maximum deviation of 3.0%. The in vivo pilot study showed a PWV before the FMD of 1.1±0.2 m/s. These results suggest that this novel MPA can reliably and accurately measure PWV within clinically relevant ranges and even well beyond.

We present a proof-of-concept design and preliminary data to demonstrate a novel syringe infusion pump that is low cost, nonelectric, reusable, and adjustable. This device addresses the need for infusion therapy in low- and middle-income countries (LMIC), where intermittent electrical power precludes the use of conventional electronic infusion pumps and limited financial resources make high costs of disposable infusion pumps impractical. Our design uses a pneumatically pressurized, hydraulic (air over oil) drive piston coupled to a closed-circuit flow restriction to drive a syringe plunger at a constant velocity, thus providing a constant volumetric flow rate to the patient. The device requires no proprietary or precision consumables, significantly reducing treatment costs compared with other methods. The highly adjustable device provides constant flow rates across the range of 0.5–8 mL/h when used with a 30-mL syringe. The user interface is simple and intuitive; the hardware is robust and portable. This novel technology platform has broad applications in addressing priority health needs in LMIC.

Cardiovascular disease (CVD), as the most prevalent human disease, incorporates a broad spectrum of cardiovascular system malfunctions/disorders. While cardiac transplantation is widely acknowledged as the optional treatment for patients suffering from end-stage heart failure (HF), due to its related drawbacks, such as the unavailability of heart donors, alternative treatments, i.e., implanting a ventricular assist device (VAD), it has been extensively utilized in recent years to recover heart function. However, this solution is thought problematic as it fails to satisfactorily provide lifelong support for patients at the end-stage of HF, nor does is solve the problem of their extensive postsurgery complications. In recent years, the huge technological advancements have enabled the manufacturing of a wide variety of reliable VAD devices, which provides a promising avenue for utilizing VAD implantation as the destination therapy (DT) in the future. Along with typical VAD systems, other innovative mechanical devices for cardiac support, as well as cell therapy and bioartificial cardiac tissue, have resulted in researchers proposing a new HF therapy. This paper aims to concisely review the current state of VAD technology, summarize recent advancements, discuss related complications, and argue for the development of the envisioned alternatives of HF therapy.

The induction of a mild reduction in body core temperature has been demonstrated to provide neuroprotection for patients who have suffered a medical event resulting in ischemia to the brain or vital organs. Temperatures in the range of 32–34 °C provide the required level of protection and can be produced and maintained by diverse means for periods of days. Rewarming from hypothermia must be conducted slowly to avoid serious adverse consequences and usually is performed under control of the thermal therapeutic device based on a closed-loop feedback strategy based on the patient's core temperature. Given the sensitivity and criticality of this process, it is important that the device control system be able to interact with the human thermoregulation system, which itself is highly nonlinear. The therapeutic hypothermia device must be calibrated periodically to ensure that its performance is accurate and safe for the patient. In general, calibration processes are conducted with the hypothermia device operating on a passive thermal mass that behaves much differently than a living human. This project has developed and demonstrated an active human thermoregulation simulator (HTRS) that embodies major governing thermal functions such as central metabolism, tissue conduction, and convective transport between the core and the skin surface via the flow of blood and that replicates primary dimensions of the torso. When operated at physiological values for metabolism and cardiac output, the temperature gradients created across the body layers and the heat exchange with both an air environment and a clinical water-circulating cooling pad system match that which would occur in a living body. Approximately two-thirds of the heat flow between the core and surface is via convection rather than conduction, highlighting the importance of including the contribution of blood circulation to human thermoregulation in a device designed to calibrate the functioning of a therapeutic hypothermia system. The thermoregulation simulator functions as anticipated for a typical living patient during both body cooling and warming processes. This human thermoregulatory surrogate can be used to calibrate the thermal function of water-perfused cooling pads for a hypothermic temperature management system during both static and transient operation.

A new type of therapeutic equipment is designed herein, using concepts of convective heat transfer and spray cooling, to treat patients suffering from brain-hyperthermia. The equipment is aimed to provide emergency treatment in order to prevent disability or possible mortality because thermoregulatory system of the patients fails to maintain a homeostasis. The equipment uses noncontact method of forced convection, applied uniformly at body exteriors. The heat exchanger is designed to contain four independent pipe-sections with orifice openings around the body. The cool-air, maintained within ASHRAE’s thermal comfort bounds, is sprayed through the orifices. Design improvements have been made on the basis of image analysis of the flow. The boundary layer (BL) analysis has also been performed over a specially designed mannequin with induced hyperthermia characteristics. The testing indicates a decay of ∼6 °C in 280 min with a time constant of 2 h. Comparative to existing techniques, in addition to being a noncontact approach, the equipment shows better thermoregulatory performance along with a flexibility to accommodate different body contours.

Anticoagulants are the treatment of choice for pulmonary embolism. When these fail or are contraindicated, vena cava filters are effective devices for preventing clots from the legs from migrating to the lung. Many uncertainties exist when a filter is inserted, especially during physiological activity such as normal breathing and the Valsalva maneuver. These activities are often connected with filter migration and vena cava damage due to the various related vein geometrical configurations. In this work, we analyzed the response of the vena cava during normal breathing and Valsalva maneuver, for a healthy vena cava and after insertion of a commercial Günther-Tulip® filter. Validated computational fluid dynamics (CFD) and patient specific data are used for analyzing blood flow inside the vena cava during these maneuvers. While during normal breathing, the vena cava flow can be considered almost stationary with a very low pressure gradient, during Valsalva the extravascular pressure compresses the vena cava resulting in a drastic reduction of the vein section, a global flow decrease through the cava but increasing the velocity magnitude. This change in the section is altered by the presence of the filter which forces the section of the vena cava before the renal veins to keep open. The effect of the presence of the filter is investigated during these maneuvers showing changes in wall shear stress and velocity patterns.

This paper introduces a new design for individually controlled magnetic artificial cilia for use in fluid devices and specifically intended to improve the mixing in DNA microarray experiments. The design has been implemented using a low-cost prototype that can be fabricated using polydimethylsiloxane (PDMS) and off-the-shelf parts and achieves large cilium deflections (59% of the cilium length). The device's performance is measured via a series of mixing experiments using different actuation patterns inspired by the blinking vortex theory. The experimental results, quantified using the relative standard deviation of the color when mixing two colored inks, show that exploiting the individual control leads to faster mixing (38% reduction in mixing time) than when operating the device in a simultaneous-actuation mode with the same average cilium beat frequency. Furthermore, the experimental results show an optimal beating pattern that minimizes the mixing time. The existence and character of this optimum is predicted by simulations using a blinking-vortex approach for 2D ideal flow, suggesting that the blinking-vortex model can be used to predict the effect of parameter variation on the experimental system.

Endovascular aneurysm repair (EVAR) is a clinically effective technique for treating anatomically eligible abdominal aortic aneurysms (AAAs), involving the deployment of an endograft (EG) that is designed to prevent blood leakage in the aneurysmal sac. While most EGs have equivalent operating principles, the hemodynamic environment established by different EGs is not necessarily the same. So, to unveil the post-EVAR hemodynamic properties, we need an EG-specific computational approach that currently lacks from the literature. Endurant and Excluder are two EGs with similar pre-installation designs. We assumed that the flow conditions in the particular EGs do not vary significantly. The hypothesis was tested combining image reconstructions, computational fluid dynamics (CFD), and statistics, taking into account the postimplantation position of the EGs. Ten patients with Endurant EGs and ten patients with Excluder EGs were included in this study. The two groups were matched with respect to the preoperative morphological characteristics of the AAAs. The EG models are derived from image reconstructions of postoperative computed tomography scans. Wall shear stress (WSS), displacement force, velocity, and helicity were calculated in regions of interest within the EG structures, i.e., the main body, the upper and lower part of the limbs. Excluder generated higher WSS compared to Endurant, especially on the lower part of the limbs (p = 0.001). Spatial fluctuations of WSS were observed on the upper part of the Excluder limbs. Higher blood velocity was induced by Excluder in all the regions of interest (p = 0.04, p = 0.01, and p = 0.004). Focal points of secondary flow were detected in the main body of Endurant and the limbs of Excluder. The displacement force acting on the lower part of the Excluder limbs was stronger compared to the Endurant one (p = 0.03). The results showed that two similar EGs implanted in similar AAAs can induce significantly different flow properties. The delineation of the hemodynamic features associated with the various commercially available EGs could further promote the personalization of treatment offered to aneurysmal patients and inspire ideas for the improvement of EG designs in the future.

The hemodynamic energy loss through the surgically implanted conduits determines the postoperative cardiac output and exercise capacity following the palliative repair of single-ventricle congenital heart defects. In this study, the hemodynamics of severely deformed surgical pathways due to torsional deformation and anastomosis offset are investigated. We designed a mock-up total cavopulmonary connection (TCPC) circuit to replicate the mechanically failed inferior vena cava (IVC) anastomosis morphologies under physiological venous pressure (9, 12, 15 mmHg), in vitro, employing the commonly used conduit materials: Polytetrafluoroethylene (PTFE), Dacron, and porcine pericardium. The sensitivity of hemodynamic performance to torsional deformation for three different twist angles (0 deg, 30 deg, and 60 deg) and three different caval offsets (0 diameter (D), 0.5D, and 1D) are digitized in three dimensions and employed in computational fluid dynamic (CFD) simulations to determine the corresponding hydrodynamic efficiency levels. A total of 81 deformed conduit configurations are analyzed; the pressure drop values increased from 80 to 1070% with respect to the ideal uniform diameter IVC conduit flow. The investigated surgical materials resulted in significant variations in terms of flow separation and energy loss. For example, the porcine pericardium resulted in a pressure drop that was eight times greater than the Dacron conduit. Likewise, PTFE conduit resulted in a pressure drop that was three times greater than the Dacron conduit under the same venous pressure loading. If anastomosis twist and/or caval offset cannot be avoided intraoperatively due to the anatomy of the patient, alternative conduit materials with high structural stiffness and less influence on hemodynamics can be considered.