A Process-Oriented Architecture for Complex System Modelling

A fine-grained massively-parallel process-oriented model of platelets (potentially artificial) within a blood vessel is presented. This is a CSP inspired design, expressed and implemented using the occam-pi language. It is part of the TUNA pilot study on nanite assemblers at the universities of York, Surrey and Kent. The aim for this model is to engineer emergent behaviour from the platelets, such that they respond to a wound in the blood vessel wall in a way similar to that found in the human body -- i.e. the formation of clots to stem blood flow from the wound and facilitate healing. An architecture for a three dimensional model (relying strongly on the dynamic and mobile capabilities of occam-pi) is given, along with mechanisms for visualisation and interaction. The biological accuracy of the current model is very approximate. However, its process-oriented nature enables simple refinement (through the addition of processes modelling different stimulants/inhibitors of the clotting reaction, different platelet types and other participating organelles) to greater and greater realism. Even with the current system, simple experiments are possible and have scientific interest (e.g. the effect of platelet density on the success of the clotting mechanism in stemming blood flow: too high or too low and the process fails). General principles for the design of large and complex system models are drawn. The described case study runs to millions of processes engaged in ever-changing communication topologies. It is free from deadlock, livelock, race hazards and starvation em by design, employing a small set of synchronisation patterns for which we have proven safety theorems

A System Utilizing Metal Hydride Actuators to Achieve Passive Motion of Toe Joints for Prevention of Pressure Ulcers: A Pilot Study

This paper describes the influence of human toe movement on blood flow and the design of a toe joint passive motion system for preventing pressure ulcers. First, we measured lower extremity blood flow in the foot during active and passive motion of the toe to facilitate the design of new rehabilitation equipment. Also, the flexion and extension angles and the force of the toe joints were measured to determine appropriate specifications for the system. Increases in blood flow were observed at the external malleolus during movement. Flexion and extension angles and the force of the toe joints were found to differ significantly among participants. It is shown that a toe joint passive motion system can be effective in preventing pressure ulcers. On the basis of these results, a device using alloys of metal hydride (MH) as an actuator that is suitable for the system to initiate toe motion, was developed

Optogenetic Interrogation and Manipulation of Vascular Blood Flow in Cortex

Understanding blood flow regulatory mechanisms that correlate the regional blood flow with the level of local neuronal activity in brain is an ongoing research. Discerning different aspects of this coupling is of substantial importance in interpretation of functional imaging results, such as functional magnetic resonance imaging (fMRI), that rely on hemodynamic recordings to detect and image brain neuronal activity. Moreover, this understanding can provide insight into blood flow disorders under different pathophysiological conditions and possible treatments for such disorders. The blood regulatory mechanisms can be studied at two different; however, complementary levels: at the cellular level or at the vascular level. To fully understand the regulatory mechanisms in brain, it is essential to discern details of the coupling mechanism in each level. While, the cellular pathways of the coupling mechanism has been studied extensively in the past few decades, our understanding of the vascular response to brain activity is fairly basic. The main objective of this dissertation is to develop proper methods and instrumentation to interrogate regional cortical vasodynamics in response to local brain stimulation. For this purpose we offer the design of a custom-made OCT scanner and the necessary lens mechanisms to integrate the OCT system, fluorescence imaging, and optogenetic stimulation technologies in a single system. The design uses off-the-shelf components for a cost-effective design. The modular design of the device allows scientists to modify it in accordance with their research needs. With this multi-modal system we are able to monitor blood flow, blood velocity, and lumen diameter of pial vessels, simultaneously. Additionally, the system design provides the possibility of generating arbitrary spatial stimulation light pattern on brain. These abilities enables researchers to capture more diverse datasets and, eventually, obtain a more comprehensive picture of the vasodynamics in the brain. Along with the device we also proposed new biological experiments that are tailored to investigate the spatio-temporal properties of the vascular response to optical neurostimulation of the excitatory neurons. We demonstrate the ability of the proposed methods to investigate the effect of length and amplitude of stimulation on the temporal pattern of response in the blood flow, blood velocity, and diameter of the pial vessels. Moreover, we offer systemic approaches to investigate the spatial characteristics of the response in a vascular network. In these methods we apply arbitrary spatial patterns of optical stimulation to the cortex of transgenic mice and monitor the attributes of surrounding vessels. With this flexibility we were able to image the brain region that is influenced by a pial artery. After characterizing the spatio-temporal properties of the vascular blood flow response to optical neuro-modulation, we demonstrate the design and application of an optogenetic-based closed-loop controller mechanism in the brain. This controller, uses a proportional–integral–derivative (PID) compensator to engineer temporal optogenetic stimulation light pulses and maintain the flow of blood at various user defined levels in a set of selected arteries. Upon tuning the gain values of the PID controller we obtained a near to critically-damped response in the blood flow of selected arterial vessels

RANCANG BANGUN SISTEM PENGAMANAN TRANSFUSI DARAH BERBASIS MIKROKONTROLER ATMega 8535

Blood warmer is a tool that is used to warm blood in the process of blood transfusion. Inside the blood warmer there are several main parts that must be considered, in the main part that must be considered is the blood fluid detector section. With the main purpose so that blood does not rise again fill the blood bag. The design of this tool aims to get the design of a security system for blood transfusion by using a photodiode detector as an indicator of blood flow that will be displayed in the form of sound. This research starts from the stages of collecting various sources, gathering information, designing tool products, designing and performing function tests. The hardware includes the design of the power supply circuit, the minimum system circuit of the ATMega8535 microcontroller, the liquid blood detector circuit, the buzzer circuit, and the servo motor circuit. While the design for software includes basic complier language programming. The working principle of the overall system is: The photodiode detector circuit will provide input to the microcontroller to be processed and produce output in the form of buzzer and servo motor closing the hos

Ultrasonic blood flow detection: Doppler techniques for obstetrics

Ultrasonic Doppler techniques have been developed for the detection of uterine blood flow. The work was undertaken to provide a noninvasive method for the study of foetal haemodynamics.The operation of the continuous wave and the pulsed wave Doppler instruments and the factors which influence their performance are discussed. The different types of Doppler signal extraction techniques which can be used with the pulsed wave Doppler are described. A design for a 2.5 MHz pulsed wave Doppler instrument is presented. The results of in vivo and in vitro trials with this instrument are presented.A blood flow instrument specially designed for examining blood flow in the pregnant uterus is described. It consists of a real time ultrasonic scanner of rotating transducer design used in conjunction with the above types of Doppler instrument. In vivo evaluation of this equipment is presented.A novel type of continuous wave Doppler instrument, the intersecting zone Doppler is described. This device overcomes the problem of lack of localisation normally associated with the continuous wave device.A composite blood flow system incorporating all three Doppler techniques is described. Blood flow spectrograms from various sites within the pregnant uterus are presented

CFD Multiphase Modeling of Blood Cells Segregation in Flow through Microtubes

Cardiovascular diseases, commonly referred as Heart Diseases, involve heart and blood vessels associated to the cardiovascular system. So called blood wetted medical devices are widely used in treatment of heart diseases as they help to provide better blood flow to patients. However, when blood is flowing through medical devices, it can be damaged due to lack of compatibility with surrounding non-biological walls of pipes, connectors and containers, thermal and osmotic effects, or most prominently due to excessive shear stresses on blood cells by medical devices. Though laboratory tests are vital for design improvements, they have proven to be costly, time intensive and ethically controversial. On the other hand, Computational Fluid Dynamics is a promising and inexpensive tool for simulating blood flow. The aim of this project is to improve and validate existing numerical model of blood cells segregation in flow through microtube. An improved numerical model of blood cells segregation is of interest for further evaluation of blood damage for design purposes of medical devices. The proposed model is based on Granular Kinetic Theory and represents a continuation of previous work by Mendygarin et al. [4] by sensitive analysis of red blood cells Sauter diameter according to local flow conditions

Computational fluid dynamic analysis of bioprinted self-supporting perfused tissue models

Natural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient‐rich oxygenated blood through the vasculature to support cell metabolism within most cell‐dense tissues. Since scaffold‐free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue‐like structures, we generated a generalizable biofabrication method resulting in self‐supporting perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO‐A5 osteoblast‐based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application before further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico

Noninvasive Blood Flow and Oxygenation Measurements in Diseased Tissue

The research presented in this dissertation focused on the application of optical imaging techniques to establish blood flow and oxygen saturation as effective biomarkers for two disease cases, Autism Spectrum Disorder (ASD) and Huntington’s Disease (HD). The BTBR mouse model of ASD was utilized to validate measurements of cerebral blood flow and oxygenation as biomarkers for autism. The R6/2 mouse model of juvenile HD was utilized to validate measurements of skeletal muscle blood flow following tetanic muscle contractions induced by electrical nerve stimulation. Next, a noncontact, camera-based system to measure blood flow and oxygen saturation maps was implemented to improve upon the previous HD mouse results by providing spatial heterogeneity in a wild-type mouse model. Finally, translational research was performed to validate a research design conducting concurrent grip strength force and skeletal muscle blood flow and oxygenation measurements in a healthy human population that will be used to establish HD biomarkers in humans in future clinical applications

Analysis and experiments on flow-induced hemolysis.

Hemolysis (red cells lysis) caused by fluid stresses in flows within hypodermic needles, blood pumps, artificial hearts and other cardiovascular devices, is one of the major concerns during the design and use of cardiovascular or blood-processing extracorporeal devices. A non-invasive experimental method which does not interfere directly with red blood cells was designed to investigate the red cells\u27 deformations in response to a range of flow conditions. The designed flow chamber and pump system provided a controlled two-dimensional Poiseuille flow with average velocity of up to 4 m/s and a range of fluid stresses up to 5000 dyn/cm 2 . The dimension of deformed cells and positions was measured to obtain the aspect ratio of red cells under stress from images captured by the microscope-laser-camera system. A strain-based blood damage model from Rand\u27s viscoelastic model was built to predict cell strain. The empirical coefficients in the blood damage model were calibrated by the measurements from the experiments. Flow-induced hemolysis in the blood flow through hypodermic needles was investigated. The flow-induced hemolysis of the needles may be reduced by a modified design of the entrance geometry of the needle. Three groups of 16 gauge needles were compared: one standard group with sharp entrance, another with beveled entrance and a third with rounded entrance. The CFD analysis combined with the strain-based blood damage model, Heuser et al. model and Giersiepen et al. model respectively was used to analyze the flow-induced hemolysis of the three needles. The predicted results were compared to the experimental results, which showed the rounded entrance reduced hemolysis by 34%, but the beveled entrance increased hemolysis by 38%. The strain-based blood damage model predicted the reduced hemolysis by 7.4% in rounded needle and the increased hemolysis by 13% in beveled needle. Both Heuser et al. model and Giersiepen et al. model predicted increased hemolysis in rounded needle