Programmable Pump Research Articles

Comparison of fluid dynamics changes due to physical activity in 3D printed patient specific coronary phantoms with the Windkessel equivalent model of coronary flow

Background3D printing (3DP) used to replicate the geometry of normal and abnormal vascular pathologies has been demonstrated in many publications; however, reproduction of hemodynamic changes due to physical activities, such as rest versus moderate exercise, need to be investigated. We developed a new design for patient specific coronary phantoms, which allow adjustable physiological variables such as coronary distal resistance and coronary compliance in patients with coronary artery disease. The new design was tested in precise benchtop experiments and compared with a theoretical Windkessel electrical circuit equivalent, that models coronary flow and pressure using arterial resistance and compliance.MethodsFive phantoms from patients who underwent clinically indicated elective invasive coronary angiography were built from CCTA scans using multi-material 3D printing. Each phantom was used in a controlled flow system where patient specific flow conditions were simulated by a programmable cardiac pump. To simulate the arteriole and capillary beds flow resistance and the compliance for various physical activities, we designed a three-chamber outlet system which controls the outflow dynamics of each coronary tree. Benchtop pressure measurements were recorded using sensors embedded in each of the main coronary arteries. Using the Windkessel model, patient specific flow equivalent electrical circuit models were designed for each coronary tree branch, and flow in each artery was determined for known inflow conditions. Local flow resistances were calculated through Poiseuille’s Law derived from the radii and lengths of the coronary arteries using CT angiography based multi-planar reconstructions. The coronary stenosis flow rates from the benchtop and the electrical models were compared to the localized flow rates calculated from invasive pressure measurements recorded in the angio-suites.ResultsThe average Pearson correlations of the localized flow rates at the location of the stenosis between each of the models (Benchtop/Electrical, Benchtop/Angio, Electrical/Angio) are 0.970, 0.981, and 0.958 respectively.Conclusions3D printed coronary phantoms can be used to replicate the human arterial anatomy as well as blood flow conditions. It displays high levels of correlation when compared to hemodynamics calculated in electrically-equivalent coronary Windkessel models as well as invasive angio-suite pressure measurements.

Therapeutic Treatment Plan Optimization during the COVID-19 Pandemic: A Comprehensive Physicochemical Compatibility Study of Intensive Care Units Selected Drugs

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. Methods: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. Results: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. Conclusions: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals.

A lab-on-a-tube biosensor for automatic detection of foodborne bacteria using rotated Halbach magnetic separation and Raspberry Pi imaging

A lab-on-a-tube biosensor was established to rapidly, sensitively and automatically detect foodborne bacteria through a rotatable Halbach magnet to form and rotate magnetic nanobead (MNB) chains for specific isolation of target bacteria, gold@platinum nanocatalysts (Au@PtNCs) to label target bacteria for efficient amplification of detection signal and Raspberry Pi App to collect and analyze the image of catalysate. First, the glass tube was successively preloaded with the mixture of MNBs, sample and Au@PtNCs, the washing buffer (skim milk) and the substrate (hydrogen peroxide-3,30,5,50-tetramethylbenzidine), and they were separated by air gaps. After the tube was placed on the biosensor, the MNB chains were stably formed and continuously rotated using the Halbach magnet and the mixture was moved back and forth using a programmable peristaltic pump, thus making the formation of MNB-bacteria-Au@PtNCs complexes. After the washing buffer was moved to wash the complexes, the substrate was then moved to resuspend the complexes, resulting in the catalytic reaction that changed the color of the substrate. Finally, the catalysate was moved to the designated area, the image of which was analyzed by the Raspberry Pi App to quantitatively determine the concentration of bacteria in the samples. This biosensor was able to detect Salmonella in spiked chicken samples in 1 h with lower detection limit of 8 CFU/50 μL and a recovery from 88.96% to 99.74%. This biosensor based on a single tube is very promising to automatically detect foodborne bacteria due to its low cost, high integration and simple operation.

Concentration on demand – A microfluidic system for precise adjustment of the content of single droplets

We present a novel microfluidic system that produces the required concentration of a reagent in a single droplet or that produces a sequence of droplets with a defined periodic distribution of concentrations. We use digital algorithms that, through a series of simple operations, such as merging and splitting droplets, ensure superior precision, repeatability and flexibility in concentration setting.Unlike Digital microfluidic (DMF) systems based on electrowetting on dielectric (EWOD) commonly used to implement digital algorithms in the droplet world, our approach is based on much more available channel-based microfluidics operated by programmable syringe pumps. Furthermore, the small footprint of our system makes it easy to integrate with other structures of microfluidic networks. Thus, this technique is a comprehensive component that can be built into the microfluidic networks executing laboratory analytical tasks in chemistry or biology to enrich their performance and offer new functionalities.

NO-HYPE: a novel hydrodynamic phantom for the evaluation of MRI flow measurements

Accurate and reproducible measurement of blood flow profile is very important in many clinical investigations for diagnosing cardiovascular disorders. Given that many factors could affect human circulation, and several parameters must be set to properly evaluate blood flows with phase-contrast techniques, we developed an MRI-compatible hydrodynamic phantom to simulate different physiological blood flows. The phantom included a programmable hydraulic pump connected to a series of pipes immersed in a solution mimicking human soft tissues, with a blood-mimicking fluid flowing in the pipes. The pump is able to shape and control the flow by driving a piston through a dedicated software. Periodic waveforms are used as input to the pump to move the fluid into the pipes, with synchronization of the MRI sequences to the flow waveforms. A dedicated software is used to extract and analyze flow data from magnitude and phase images. The match between the nominal and the measured flows was assessed, and the scope of phantom variables useful for a reliable calibration of an MRI system was accordingly defined. Results showed that the NO-HYPE phantom is a valuable tool for the assessment of MRI scanners and sequence design for the MR evaluation of blood flows.Graphical abstractOverview of the NOvel HYdrodynamic Phantom for the Evaluation of MRI flow measurements (NO-HYPE). Left: internal of the CompuFlow 1000 MR pump unit. Right: Setting of the NO-HYPE before a MRI acquisition session. Soft tissue mimicking material is hosted in the central part of the phantom (light blue chamber). Glass pipes pass through the chamber carrying the blood mimicking fluid.

Ender3 3D printer kit transformed into open, programmable syringe pump set

A cheap, open source 3D printer (Creality Ender 3) is transformed into an Open Hardware, programmable syringe pump set. Only 3 parts need to be purchased outside of the printer kit. All other parts are either in the Ender 3 kit, or can be 3D printed. No prior knowledge in electronics or programming languages is required. The pumps are controlled by the 3D printer firmware and motherboard and programmed in simple G-code text files. The total cost of a three pumps setup is ∼€170. The pumps are capable of reaching stable flows down to 5 µL/min using cheap, disposable 10 mL syringes. Higher flow speeds are also achievable, in the order of mL/min.

Programmable Pump for Intrathecal Morphine Delivery to Cisterna Magna: Clinical Implications in Novel Management of Refractory Pain Above Middle Thoracic Vertebrae Level Utilizing a Prospective Trial Protocol and Review.

BackgroundThe cisterna Intrathecal Drug Delivery system (IDDS) with morphine has proven to be effective in treating refractory cancer pain above the middle thoracic vertebrae level in some countries. However, it has not been fully investigated in others. We designed the current project to investigate the efficacy and safety of cisterna IDDS for pain relief in refractory pain above the middle thoracic vertebrae level in advanced cancer patients.MethodsThis study protocol allows for eligible cancer patients to receive the cisterna IDDS operation. Pain intensity (Visual Analogue scale, VAS), quality of life (36-Item Short-Form Health Survey, SF-36), and depression (Self-Rating Depression scale, SDS) are assessed along with side effects in the postoperative follow-up visits. Recent literature suggests a potential role for cisterna IDDS morphine delivery for refractory pain states above the middle thoracic level.ConclusionThe results of this study may provide further evidence that cisterna IDDS of morphine can serve as an effective and safe pain relief strategy for refractory pain above the middle thoracic vertebrae level in advanced cancer patients.

Design of non-autonomous pH oscillators and the existence of chemical beat phenomenon in a neutralization reaction

The beat in physical systems is a transparent and well-understood phenomenon. It may occur in forced oscillatory systems and as a result of the interference of two waves of slightly different frequencies. However, in chemical systems, the realization of the latter type of the beat phenomenon has been lacking. Here we show that a periodic titration of acid and alkaline solutions with each other using programmable syringe pumps in a continuous stirred-tank reactor exhibits the beat phenomenon in the temporal pH oscillation pattern if the time periods of sinusoidal inflow rates of the reagents are slightly different. Interestingly, the frequency of the chemical beat pattern follows the well-known relationship from physics, namely the frequency of the beat is equal to the absolute value of the difference of the two wave frequencies. Based on our strategy, we can design and engineer non-autonomous pH oscillatory systems, in which the characteristics of the temporal oscillations (amplitude, time period) can easily and precisely be controlled by the experimental conditions such as the inflow rates and feed concentrations. The demonstrated phenomena can be exploited in practical applications, we use the non-autonomous pH oscillators to drive the reversible assembly and disassembly of pH-sensitive building blocks (oleic acid and gold nanoparticles), both highly relevant in nanotechnology and biomedical applications.

An automated image analysis platform for the study of weakly -adhered cells

Details of the design and implementation of an open-source platform for studying the adhesion of cells attached to solid substrata are provided. The hardware is based on a laser-cut flow channel connected to a programmable syringe pump. The software automates all aspects of the flow rate profile, data acquisition and image analysis. An example of the pelagic diatom Thalassiosira rotula adhered to poly(dimethyl siloxane) surfaces is provided. The procedure described enables the shear rate to be converted to drag force for arbitrary-shaped objects, of utility to the study of many cell species, especially ones that are obviously non-spherical. It was determined that 90% of cells are removed with the application of drag forces < N, and that this value is relatively independent of the incubation time on the surface. This result is important to understand how marine species interact with polymer surfaces that are used in electrical insulator applications.

Assessment of OTT Pluvio2 Rain Intensity Measurements

AbstractThis study investigates the OTT Pluvio2 weighing precipitation gauge’s random and systematic error components as well as stabilization of the measurements on time-varying rainfall intensities (RI) under laboratory conditions. A highly precise programmable peristaltic pump that provided both constant and time-varying RI was utilized in the experiments. Abrupt, gradual step, and cyclic step changes in the RI values were evaluated. RI readings were taken in real time (RT) at different time resolutions (6–60 s) for the RI range of 6–70 mm h−1. Our analysis indicates that the lower threshold for the OTT Pluvio2’s real-time RI measurements should be redefined as 7 mm h−1 at a 1-min resolution. Tolerance intervals containing 95% of the repeated measurements with a probability of 0.95 are given. It is shown that the measurement variances are unequal over the range of RI and the measurement repeatability is not uniform. A statistically significant negative bias was observed for the RI values of 7 and 8 mm h−1, while there was not a statistically significant linearity problem. Through the use of statistical control limits, it is shown that means of the RI measurements stabilized on the actual RI value. A detailed investigation on RT bucket weight measurements revealed a time delay in bucket weight measurements, which causes notable errors in reported RI measurements under dynamic rainfall conditions. To demonstrate the potentiality of large errors in Pluvio2’s real-time RI measurements, a set of equations was developed that faithfully reproduced the Pluvio2’s internal (hidden) algorithm, and results from dynamic laboratory and in situ rainfall scenarios were simulated. The results of this investigation show the necessity of modifying the present Pluvio2 RI algorithm to enhance its performance and show the possibility of postprocessing the existing Pluvio2 RI datasets for improved measurement accuracies.

Low-cost, programmable infusion pump with bolus mode for in-vivo imaging

Syringe pumps are routinely used in biomedical imaging laboratories for delivering contrast agents and either infusing or injecting a precise amount of liquids. Commercial syringe pumps that are developed by specialized companies are expensive and only have standard functions, which often do not meet the requirements of individual experiments. In this paper, we demonstrate an open–source single syringe pump with the possibility of adapting to the needs of a researcher. The device that was designed, is controlled by an Arduino Leonardo, along with the stepper motor driver. For sending commands and receiving the current plunger position, a C# software was developed with serial communication via USB. Additionally, the 3D models were made in a universal way, which allows for the use of any syringe size. An example of the application of the syringe pump for biomedical applications was demonstrated using electron resonance imaging (ERI). The single syringe pump tests were demonstrated by simulating the filling of a particular volume inside the resonator. This example reflects the clearance process after an intravascular (I.V) drug administration in the murine model. The experiments were performed on an ERI TM 600 tomograph. The results confirmed that the designed syringe pump allowed for controlling the infusion speed and injected volume. Moreover, we present a user-friendly and open-source graphical interface that is a low-cost alternative for commercial devices.

Vortex dynamics and transport phenomena in stenotic aortic models using Echo-PIV

Atherosclerosis is the most fatal cardiovascular disease. As disease progresses, stenoses grow inside the arteries blocking their lumen and altering blood flow. Analysing flow dynamics can provide a deeper insight on the stenosis evolution. In this work we combined Eulerian and Lagrangian descriptors to analyze blood flow dynamics and fluid transport in stenotic aortic models with morphology, mechanical and optical properties close to those of real arteries. To this end, vorticity, particle residence time (PRT), particle's final position (FP) and finite time Lyapunov's exponents (FTLE) were computed from the experimental fluid velocity fields acquired using ultrasonic particle imaging velocimetry (Echo-PIV). For the experiments, CT-images were used to create morphological realistic models of the descending aorta with 0%, 35% and 50% occlusion degree with same mechanical properties as real arteries. Each model was connected to a circuit with a pulsatile programmable pump which mimics physiological flow and pressure conditions. The pulsatile frequency was set to ≈0.9 Hz (55 bpm) and the upstream peak Reynolds number (Re) was changed from 1100 to 2000. Flow in the post-stenotic region was composed of two main structures: a high velocity jet over the stenosis throat and a recirculation region behind the stenosis where vortex form and shed. We characterized vortex kinematics showing that vortex propagation velocity increases with Re. Moreover, from the FTLE field we identified Lagrangian coherent structures (i.e. material barriers) that dictate transport behind the stenosis. The size and strength of those barriers increased with Re and the occlusion degree. Finally, from the PRT and FP maps, we showed that independently of Re, the same amount of fluid remains on the stenosis over more than a pulsatile period.

Novel semi-automated graphene nanosheets based pipette-tip assisted micro-solid phase extraction as eco-friendly technique for the rapid detection of emerging environmental pollutant in waters

In this work, a new semi-automated syringe infusion-pump assisted graphene nanosheets (GNSs) based pipette-tip micro-solid phase extraction (PT-μSPE) as a green sample preparation technique was demonstrated for the sensitive analysis of emerging environmental pollutant in environmental waters using HPLC-UV. Microwave-assisted synthesized GNSs powder was packed into a 100 μL pipette-tip (as PT-μSPE cartridge) connected with a commercial plastic syringe (contains water sample). This setup was attached to a programmable auto-syringe infusion pump for the GNSs-PT-μSPE process. Triclosan (TCS) is an emerging environmental pollutant chosen as a target analyte to examine the extraction capacity and feasibility of GNSs as a sorbent material for PT-μSPE. Parameters affecting the extraction capability were systematically evaluated and thoroughly optimized. At optimized experimental parameters, excellent linearity (r2 = 0.9979) was achieved over the concentration range of 2–250 ng mL−1 for TCS, with a detection limit of 0.5 ng mL−1. Applicability of the presented method was examined with real water samples, and extraction recoveries obtained were ranged between 94.6–102.4% with RSD less than 7.8%. The presented protocol is a simple, semi-automated, eco-friendly, low-cost, and efficient sample pretreatment technique for quick analysis of TCS in environmental wastewaters.

Challenges in hemodynamics assessment in complex neurovascular geometries using computational fluid dynamics and benchtop flow simulation in 3D printed patient specific phantoms.

Complex hemodynamics assessments, as those related to carotid stenosis, are not always easily straightforward due to multifaceted challenges presented by the collateral flow in the Circle of Willis (CoW) and brain flow autoregulation. Advanced computational and benchtop methods to investigate hemodynamics aspects related to such complex flows are often used, however both have limitations and could lead to results which may diverge. In this study we investigated these aspects by performing correlated computational fluid dynamics (CFD) simulations and benchtop experiments in patient specific 3D printed phantoms. To investigate the flow in patients with carotid stenosis, we built two patient specific phantoms which contained the arterial lesion of interest, all main arteries leading to the brain, the CoW and main arteries branching from it. Each phantom was connected to a generic aortic arch. A programmable pump was connected and flow parameters were measured proximal and distal to the lesion and the contralateral arteries. The patient 3D geometry was used to perform a set of CFD simulations where inflow boundary conditions matched the experimental ones. Flow conditions were recorded at the same locations as the experimental setup. Further exploration into the translation from experimental to CFD was also performed by customizing vascular segmentation and physically manipulating arterial compliance properties. We initially observed significant differences between the CFD recordings and the experimental setup. Most of the differences were due to changes in phantom geometry when subjected to physiological pressures and simplistic outflow boundary conditions in the CFD simulations which do not account for pulsatility and nonlinear phenomena. Further work confirms the need for dynamic mesh behavior within CFD simulations attempting to computationally mimic 3D-printed benchtop experiments. Additionally, CFD simulation may benefit from considering geometry specific to a 3D-printed vascular phantom.

Design of Radial Artery Simulation Platform Based on Waveform Drive

In order to obtain the three-dimensional pulse information and blood pressure waveform needed in the study, a radial artery simulation platform with programmable controlled injection pump as the core was constructed by using the circulation theory of human cardiovascular system and pulse wave formation mechanism. Gaussian function model was selected to synthesize multi-type pulse wave to program and drive the platform. The three-dimensional pulse information and blood pressure waveform of the simulated radial artery were collected by binocular visual pulse detection system and pressure transmitter respectively, and the platform stability and repeatability were tested by Pearson correlation. The experimental results show that the radial artery simulation platform is stable, reliable and repeatable, and can generate multiple types of three-dimensional pulse information and blood pressure waveform at the simulated radial artery. The platform is simple in structure, low in cost, and produces many types of pulsating flow. It provides an experimental research platform for revealing the relationship between the three-dimensional pulse information of radial artery and the change of pressure inside the vessel, as well as the prediction of blood pressure waveform from the three-dimensional pulse information.

Modular Microphysiological System for Modeling of Biologic Barrier Function.

Microphysiological systems, also known as organs-on-chips, are microfluidic devices designed to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to established microfabrication methods, and properties that make it suitable for biological applications such as low cytotoxicity, optical transparency, gas permeability. However, absorption of small molecules and leaching of uncrosslinked oligomers might hinder the adoption of PDMS-based organs-on-chips for drug discovery assays. Here, we have engineered a modular, PDMS-free microphysiological system that is capable of recapitulating biologic barrier functions commonly demonstrated in PDMS-based devices. Our microphysiological system is comprised of a microfluidic chip to house cell cultures and pneumatic microfluidic pumps to drive flow with programmable pressure and shear stress. The modular architecture and programmable pumps enabled us to model multiple in vivo microenvironments. First, we demonstrate the ability to generate cyclic strain on the culture membrane and establish a model of the alveolar air-liquid interface. Next, we utilized three-dimensional finite element analysis modeling to characterize the fluid dynamics within the device and develop a model of the pressure-driven filtration that occurs at the glomerular filtration barrier. Finally, we demonstrate that our model can be used to recapitulate sphingolipid induced kidney injury. Together, our results demonstrate that a multifunctional and modular microphysiological system can be deployed without the use of PDMS. Further, the bio-inert plastic used in our microfluidic device is amenable to various established, high-throughput manufacturing techniques, such as injection molding. As a result, the development plastic organs-on-chips provides an avenue to meet the increasing demand for organ-on-chip technology.

A SAR-ADC-Assisted DC-DC Buck Converter With Fast Transient Recovery

This brief presents a successive-approximation-register (SAR) analog-to-digital converter (ADC) assisted DC-DC buck converter, which operates in discontinuous conduction mode (DCM) and achieves fast load transient recovery characteristics. The power inductor of the buck converter uses the bondwire inductance. During the load transient, the dynamic low-power SAR ADC samples the converter's undershoot/overshoot output voltage and controls the programmable current pump circuit to charge/discharge the output capacitor, thus speeding up and smoothing the load transient response. An additional compensation circuit is also designed to ensure the stability of the voltage mode control loop and the current pump. The chip fabricated in a 65-nm CMOS technology occupies an area of 1 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The converter, switching at 100 MHz, achieves a peak power efficiency of 81% when V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">IN</sub> = 1.2 V, V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OUT</sub> = 1 V and I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Load</sub> = 50 mA. When the load current steps from 2 mA to 50 mA, the measured undershoot/overshoot voltage is 101/92 mV, and the recovery time is 175/406 ns.

A microfluidic platform enabling real-time control of dynamic biochemical stimuli to biological cells

In the present study, we report a microfluidic platform that enables real-time control of biochemical stimuli to biological cells. The microfluidic platform is designed by integrating a ‘Christmas tree’ inlet for pre-generating spatially linear concentration gradient, with a Y-shaped channel to modulate dynamic signals with an external programmable air pump. The proposed design is simple and straightforward, has negligible response time compared to the traditional Y-shaped channel, and for the first time, provides the capability of generating versatile waveforms of dynamic stimuli and implementing multiple dynamic stimulating signals with different amplitudes synchronously. The feasibility of the microfluidic platform is proved by both computational fluid dynamics simulation and fluorescein experiment. The applicability of the proposed platform is demonstrated by characterizing the intracellular calcium ion dynamics in human umbilical vein endothelial cells in response to multiple dynamic stimuli within a single run. The proposed platform provides a simple approach to rapidly control dynamic stimuli with versatile waveforms to biological cells and shows the potential for the quantitative study of biological cellular dynamic responses.

Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study.

We studied the feasibility, safety, tolerability and pharmacokinetics of intracerebroventricular delivery of recombinant human vascular endothelial growth factor in patients with amyotrophic lateral sclerosis. In this phase I study in patients with amyotrophic lateral sclerosis, the study drug was delivered using an implantable programmable pump connected to a catheter inserted in the frontal horn of the lateral cerebral ventricle. A first cohort received open label vascular endothelial growth factor (0.2, 0.8 and 2 µg/day), a second cohort received placebo, 0.8 or 2 µg/day of study dug. After the 3-month study period, all patients could participate in an open label extension study. In total, 18 patients with amyotrophic lateral sclerosis, seen at the University Hospitals in Leuven were included. The surgical procedure was well tolerated in most patients. One patient had transient postoperative seizures, due to an ischemic lesion along the catheter tract. The first 3-month study period was completed by 15/18 patients. Administration of 2 µg/day vascular endothelial growth factor resulted in sustained detectable levels in cerebrospinal fluid. A pulmonary embolus occurred in 3 patients, in 1 patient in the first 3-month study, and in 2 patients during the open label extension study. The study drug was well tolerated in the other patients, for up to 6 years in the open label extension study. Our study shows that intracerebroventricular administration of 2 µg/day of vascular endothelial growth factor to patients with amyotrophic lateral sclerosis is feasible, results in detectable cerebrospinal fluid levels and is well tolerated in most patients. The most common serious adverse event was a pulmonary embolus.

Patient-specific 3D-printed coronary models based on coronary computed tomography angiography volumes to investigate flow conditions in coronary artery disease

Background: 3D printed patient-specific coronary models have the ability to enable repeatable benchtop experiments under controlled blood flow conditions. This approach can be applied to CT-derived patient geometries to emulate coronary flow and related parameters such as Fractional Flow Reserve (FFR). Methods: This study uses 3D printing to compare such benchtop FFR results with a non-invasive CT-FFR research software algorithm and catheter based invasive FFR (I-FFR) measurements. Fifty-two patients with a clinical indication for I-FFR underwent a research Coronary CT Angiography (CCTA) prior to catheterization. CT images were used to measure CT-FFR and to generate patient-specific 3D printed models of the aortic root and three main coronary arteries. Each patient-specific model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for two coronary outflow rates (‘normal’, 250 ml min−1; and ‘hyperemic’, 500 ml min−1) by adjusting the model’s distal coronary resistance. Results: Pearson correlations and ROC AUC were calculated using invasive I-FFR as reference. The Pearson correlation factor of CT-FFR and B-FFR-500 was 0.75 and 0.71, respectively. Areas under the ROCs for CT-FFR and B-FFR-500 were 0.80 (95%CI: 0.70–0.87) and 0.81 (95%CI: 0.64–0.91) respectively. Conclusion: Benchtop flow simulations with 3D printed models provide the capability to measure pressure changes at any location in the model, for ultimately emulating the FFR at several simulated physiological blood flow conditions. Clinical Trial Registration: https://clinicaltrials.gov/show/NCT03149042