Flow Modeling - Computational Fluid Dynamics (CFD) - Life Sciences
Fluids, fluid dynamics, and associated transport phenomena loom large within medicine and life sciences because the field has evolved to use them as building blocks, components, and subsystems, as well as mechanisms of signaling, sustenance, regeneration, and destruction. Furthermore, as we have developed means of engineering life through medical devices, pharmaceuticals, and biologics, the same pathways and physical forms were used for the delivery of our work product (as in catheters, implantable artificial hearts, solutions, and inhaled biologics). Hence, understanding and predicting fluid behavior and transport has become a differentiated advantage for companies that operate within the medical device, pharmaceuticals, and biologics sectors of the life sciences industry. Computational Fluid Dynamics (CFD) is the name of the set of tools that enable fluid behavior prediction. These set of tools have been utilized within Life Sciences to stress-test the design before prototyping, reduce the volume of in-vitro tests with blood and other biological fluids, reduce the need for pre-clinical testing, assess the product function at and beyond the established design boundaries and to elucidate failure mechanisms during root cause analysis. Exponent has expertise in Computational Fluid Dynamics (CFD) analysis for the life sciences industry using state-of-the-art model definition and analysis software (MIMICS, ScanIP, ANSYS® [Fluent], COMSOL®, STAR CCM+®, openfoam, and custom codes).
Exponent professionals have robust experience in life science product development and hence are able to deploy CFD within the framework of other computer aided engineering tools (computer aided design [CAD], reverse engineering/domain definition, multi-physics modeling, additive manufacturing for prototype generation, computer aided manufacturing [CAM] and testing [CAT]).
Blood Flow and Fluid Path Analysis
Exponent engineers use CFD models to characterize and evaluate medical device performance for non-implanted cardiovascular (oxygenation, heat exchangers, cardiotomy reservoirs, filters), neurovascular (embolization catheters), pulmonary, dialysis (peritoneal dialysis [PD] and hemo-), membrane/centrifugal and magnetic cell separation, blood collection and transfusion, IV administration, and ENT applications.
Our team has considerable experience understanding hemodynamics and blood-device interactions. Modeling efforts have focused on understanding device priming characteristics, ability of the device to mitigate air and gas, localized shear rate, shear stress and pressure of blood and its components and its effect on biological phenomena such as blood damage and trauma, hemolysis, depletion of oxygen and nutrients, build-up of waste products, and localized clotting. Specific work has included the following:
- Hydrodynamics and thermal simulation of cardiac ablation catheters.
- Evaluation of localized shear stress in the fluid path to avoid shear-induced hemolysis.
- Identification of stagnant regions and regions of secondary flow where blood flow recirculates locally may cause shear-induced trauma, hypoxemia, and accumulation of toxic agents and localized thrombus formation.
- Assessment of the heating and cooling of blood and biological fluids to examine potential for denaturing protein components or freezing of the aqueous phase.
- Identification of a lack or incompleteness of fluid-path priming to minimize the inability to initiate flow, degradation flow rate, loss of flow accuracy, and flow stoppage during clinical use.
- Generation of models to assess device capability in handling dissolved gases or incipient gas bubbles through bubble traps.
- Generation of coupled fluid dynamics and transport models for peritoneal and hemodialysis, where ultrafiltration and marker solutes were of interest.
- Generation of models for a membrane device to separate plasma into high- and low-molecular-weight fractions.
- Development of models for plasmapheresis through a Taylor-Vortex device, including effects of cell-based fouling of the membrane.
Exponent has developed structural FEA and CFD models of various cardiovascular implants for evaluating design, manufacturing, and delivery procedures, along with clinical performance. This core competency is also complemented with our stent and valve testing experimental capability as well as MRI qualification core competency.
Modeling experience includes the following:
- Artificial heart valves and devices (percutaneous (TAVI/TAVR) and surgically placed) to assess dead-zones, hemolysis levels and pressures on the valve leaves.
- Bridge to implant or destination therapy LVADs
- Cardiovascular and peripheral stents—self-expanding and balloon expanding
- Vena cava filters
- Abdominal aortic aneurysm (AAA) grafts
- Ventricular reconstruction modeling
- Device-life predictions using implant/vessel interaction models
Flow Within Containers and Devices
Exponent engineers have developed computational strategies and methods for flow of solutions and therapeutics (pharmaceuticals and biologics) in flexible containers, syringes, and custom unit dosage forms; as well as through devices from which the products were delivered.
- Conducting handling and drainage analysis of flexible containers during use
- Ad-mix and reconstitution analysis of lyophilized drug forms into flexible containers using vial access devices or coupling systems
- Reconstitution flow and foam generation analysis during the preparation of high-risk pharmaceuticals (oncolytics) or biologics presented in glass vial dose form
- Delivery of strongly non-newtonian (shear thinning, denaturing, or viscoelastic) homogeneous or particle-loaded solutions.
- Modeling, characterization and development support for various pumping systems, including linear peristaltic pumps, cassette-based membrane pumps for blood component separation and dialysis, piston-based pumps for biologics delivery, and curvilinear or shuttle-based peristalsis-based pumps for infusion
- Modeling of disposable components and sub-systems for access, valving, sensing, and control of the fluid flow through devices
Hemostats, Surgical Sealants, and Glues
Exponent has developed modeling capabilities to understand the physics of delivery, risks attending to the delivery (such as gas embolism in pneumatically assisted spray devices) and sealing capabilities of biomaterials that are used as hemostats, surgical sealants, and glues.
Drug Delivery Systems
Exponent also has expertise in the performance evaluation and optimization of devices, including inhalation delivery systems such as propellant metered dose inhalers (pMDIs), dry powder inhalers (DPIs), and nebulizers, as well as diffusion-based drug delivery.
Modeling experience includes the following:
- Oral, transdermal, and buccal deliveries
- Medication delivery pumps
- Elastomeric infusion pumps
- Analysis of air flow through respiratory cavities, including the nasal cavity, trachea, and lungs
- Analysis of drug distribution in the spinal CSF space
- Controlled-release polymers and hydrogels, drug elution from stents
Manufacturing and Distribution Processes
Exponent engineers have modeling expertise that has been leveraged successfully in manufacturing and distribution processes, as they are able to combine knowledge of coupled fluid dynamics with transport processes and understanding of manufacturing environment complexity.
Some examples are:
- Development of models for manual and automated filling lines to reduce splashing, foaming, and control of liquid and air-space tolerances, including form-fill-seal (FFS) environments
- Development of thermal models in support of a first-in-class flexible-container biologics regulatory submission, to assess total thermal load on the product during manufacturing
- Modeling of the lyophilization process phases
- Developing heat-sealing models for flexible container manufacturing
- Modeling container-specific temperature distribution during moist heat sterilization for identification of cold spots, assessing F0 values, and predicting solute degradation using first-order kinetics
- Modeling low-power e-beam sterilization systems to understand shadowing effects and support gun development to reduce replacement costs
- Modeling warehouses to understand heat history variations in the product post-sterilization
- Modeling pallet loads during shipping to understand bounds of product temperature excursions as a function of shipping/storage ambient temperature and conditions.