Current status of the development of wireless sensors for medical applications]

Wireless near-field transmission has been a challenge for scientists developing medical sensors for a long time. Here, instruments which measure a patient's ECG, oxygen saturation, blood pressure, peak flow, weight, blood glucose etc. are to be equipped with suitable transmission technology. Application scenarios for these sensors can be found in all medical areas where cable connections are irritating for the doctor, patient and other care personnel. This problem is especially common in sport medicine, sleep medicine, emergency medicine and intensive care. Based on its beneficial properties with regard to power consumption, range, data security and network capability, the worldwide standard radio technology Bluetooth was selected to transmit measurements. Since digital data is sent to a receiving station via Bluetooth, the measurement pre-processing now takes place in the patient sensor itself, instead of being processed by the monitor. In this article, a Bluetooth ECG, Bluetooth pulse oximeter, Bluetooth peak flow meter and Bluetooth event recorder will be introduced. On the one hand, systems can be realized with these devices, which allow patients to be monitored online (ECG, pulse oximeter). These devices can also be integrated in disease management programs (peak flow meter) and can be used to monitor high-risk patients in their home environment (event recorder).     

Chronic implantation of transit-time flow probes on the ascending aorta of rodents

This study describes the implantation of transit-time flow probes on the ascending aorta of rats while minimizing the risk of postoperative complications. Special emphasis is placed on our new method of rat intubation as well as the production of materials necessary for the implantation procedure such as endotracheal tubes and heparin bonded vessel catheters. The effects of these devices on the response to acute hypoxia were studied in rats following a 5-7 day recovery from the implantation procedure. Systemic and microvascular measurements were made on instrumented rats (n = 5) and non-instrumented controls (n = 3) that were ventilated with 21%, 15%, 10%, 8% and 5% oxygen. Arterial pressure, PO(2), lactate, and base deficit were not different between the implanted and control animals at any inspired oxygen concentration. Microvascular flow in the primary arterioles of the spinotrapezius muscle was also similar between the two groups at all inspired oxygen concentrations. We conclude that this novel methodology facilitates the measurement of whole body oxygen delivery in resting and haemodynamically-stressed rats.     

Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling

The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges to (equivalent to to ) and to (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells.     

Lactate delivery (not oxygen) limits hepatic gluconeogenesis when blood flow is reduced

The purpose of this study was to determine, using the isolated liver perfusion technique, whether the limiting factor for hepatic gluconeogenesis (GNG) from lactate was precursor delivery or oxygen availability during reduced flow rates of 0.85 or 0.60 ml.min(-1).g liver(-1). After a 24-h fast, three different experimental protocols were employed. Protocol 1 examined the impact on GNG when reservoir lactate concentration was maintained but oxygen delivery was elevated via increases in hematocrit (Hct). Elevating the Hct from 22.5+/- 0.8% to 30.9+/- 0.4% at a blood flow of 0.89+/- 0.01 ml.min(-1).g liver(-1) increased the oxygen consumption (Vo(2)) but did not augment GNG. Similarly, when the Hct was elevated from 22.5+/- 0.8% to 41.5+/- 0.7% at 0.59+/- 0.04 ml.min(-1).g liver(-1), Vo(2) was increased, but GNG was unaffected. Protocol 2 examined the impact on GNG when Hct was maintained but precursor delivery was elevated via increases in reservoir lactate concentration ([LA]). Specifically, elevating the [LA] from 2.31+/- 0.07 to 3.61+/- 0.33 mM at a flow rate of 0.82+/- 0.04 ml.min(-1).g liver(-1) significantly increased GNG. Similarly, elevating the [LA] from 2.31+/- 0.07 to 4.24+/- 0.37 mM at a flow rate of 0.58+/- 0.02 ml.min(-1).g liver(-1) increased GNG. Finally, we examined the impact of increasing both the oxygen and lactate delivery (Protocol 3). Again, Vo(2) was elevated with increased oxygen delivery, but GNG was not augmented beyond that observed with elevations in lactate delivery alone, i.e., Protocol 2. The results indicate that, during decrements in blood flow, GNG is limited primarily by precursor delivery, not oxygen availability.     

Pulsatile blood flow and oxygen transport past a circular cylinder

The fundamental study of blood flow past a circular cylinder filled with an oxygen source is investigated as a building block for an artificial lung. The Casson constitutive equation is used to describe the shear-thinning and yield stress properties of blood. The presence of hemoglobin is also considered. Far from the cylinder, a pulsatile blood flow in the x direction is prescribed, represented by a time periodic (sinusoidal) component superimposed on a steady velocity. The dimensionless parameters of interest for the characterization of the flow and transport are the steady Reynolds number (Re), Womersley parameter (alpha), pulsation amplitude (A), and the Schmidt number (Sc). The Hill equation is used to describe the saturation curve of hemoglobin with oxygen. Two different feed-gas mixtures were considered: pure O(2) and air. The flow and concentration fields were computed for Re=5, 10, and 40, 0< or =A< or =0.75, alpha=0.25, 0.4, and Schmidt number, Sc=1000. The Casson fluid properties result in reduced recirculations (when present) downstream of the cylinder as compared to a Newtonian fluid. These vortices oscillate in size and strength as A and alpha are varied. Hemoglobin enhances mass transport and is especially important for an air feed which is dominated by oxyhemoglobin dispersion near the cylinder. For a pure O(2) feed, oxygen transport in the plasma dominates near the cylinder. Maximum oxygen transport is achieved by operating near steady flow (small A) for both feed-gas mixtures. The time averaged Sherwood number, Sh, is found to be largely influenced by the steady Reynolds number, increasing as Re increases and decreasing with A. Little change is observed with varying alpha for the ranges investigated. The effect of pulsatility on Sh is greater at larger Re. Increasing Re aids transport, but yields a higher cylinder drag force and shear stresses on the cylinder surface which are potentially undesirable.     

Micro- and nanofabrication methods in nanotechnological medical and pharmaceutical devices

Micro- and nanofabrication techniques have revolutionized the pharmaceutical and medical fields as they offer the possibility for highly reproducible mass-fabrication of systems with complex geometries and functionalities, including novel drug delivery systems and bionsensors. The principal micro- and nanofabrication techniques are described, including photolithography, soft lithography, film deposition, etching, bonding, molecular self assembly, electrically induced nanopatterning, rapid prototyping, and electron, X-ray, colloidal monolayer, and focused ion beam lithography. Application of these techniques for the fabrication of drug delivery and biosensing systems including injectable, implantable, transdermal, and mucoadhesive devices is described.     

Transmural flow bioreactor for vascular tissue engineering

Nutrient transport limitation remains a fundamental issue for in vitro culture of engineered tissues. In this study, perfusion bioreactor configurations were investigated to provide uniform delivery of oxygen to media equivalents (MEs) being developed as the basis for tissue‐engineered arteries. Bioreactor configurations were developed to evaluate oxygen delivery associated with complete transmural flow (through the wall of the ME), complete axial flow (through the lumen), and a combination of these flows. In addition, transport models of the different flow configurations were analyzed to determine the most uniform oxygen profile throughout the tissue, incorporating direct measurements of tissue hydraulic conductivity, cellular O₂ consumption kinetics, and cell density along with ME physical dimensions. Model results indicate that dissolved oxygen (DO) uniformity is improved when a combination of transmural and axial flow is implemented; however, detrimental effects could occur due to lumenal pressure exceeding the burst pressure or damaging interstitial shear stress imparted by excessive transmural flow rates or decreasing hydraulic conductivity due to ME compaction. The model was verified by comparing predicted with measured outlet DO concentrations. Based on these results, the combination of a controlled transmural flow coupled with axial flow presents an attractive means to increase the transport of nutrients to cells within the cultured tissue to improve growth (increased cell and extracellular matrix concentrations) as well as uniformity. Biotechnol. Bioeng. 2009; 104: 1197–1206. © 2009 Wiley Periodicals, Inc.     

Optimization of shunt placement for the Norwood surgery using multi-domain modeling

An idealized systemic-to-pulmonary shunt anatomy is parameterized and coupled to a closed loop, lumped parameter network (LPN) in a multidomain model of the Norwood surgical anatomy. The LPN approach is essential for obtaining information on global changes in cardiac output and oxygen delivery resulting from changes in local geometry and physiology. The LPN is fully coupled to a custom 3D finite element solver using a semi-implicit approach to model the heart and downstream circulation. This closed loop multidomain model is then integrated with a fully automated derivative-free optimization algorithm to obtain optimal shunt geometries with variable parameters of shunt diameter, anastomosis location, and angles. Three objective functions: (1) systemic; (2) coronary; and (3) combined systemic and coronary oxygen deliveries are maximized. Results show that a smaller shunt diameter with a distal shunt-brachiocephalic anastomosis is optimal for systemic oxygen delivery, whereas a more proximal anastomosis is optimal for coronary oxygen delivery and a shunt between these two anatomies is optimal for both systemic and coronary oxygen deliveries. Results are used to quantify the origin of blood flow going through the shunt and its relationship with shunt geometry. Results show that coronary artery flow is directly related to shunt position.     

Respiration rate in human primary renal proximal and early distal tubular cells in vitro: considerations for biohybrid renal devices

Background: For biotechnological use of cells in tissue engineered applications, such as biohybrid renal devices, optimal culture conditions are required. Oxygen delivery is one of the most important cell determined system criterion for ex vivo applications. It is involved in the maintenance of highly oxygen‐dependent renal tubular epithelial cells, affecting metabolic state, differentiation, and desired transport functions. The purpose of this study was to examine respiratory patterns such as basal oxygen consumption, solute transport‐related oxygen demand, and oxygen concentration‐dependent oxygen uptake of renal tubular epithelial cells in vitro. Methods: Respiratory patterns of highly purified human primary renal proximal (hPTC) and early distal tubular cells (hTALDC) were analyzed by perfusion respirometry. Spontaneous oxygen consumptions and maximum respirations after carbonyl cyanide m‐chlorophenyl hydrazone (CCCP) uncoupling were measured. Respiration fractions contributing to basolateral Na⁺/K⁺‐ATPase transport activities were assessed via ouabain inhibition and Na⁺‐free medium. Furthermore, we determined oxygen uptake in dependency of oxygen concentration and morphology in various culture conditions (shaken, static). Results: Respiration of solely hPTC strongly depended on oxygen concentration in a Michaelis‐Menten pattern at noncritical oxygen concentrations. Respiration of both cell types was significantly increased by CCCP, whereas average Na⁺/K⁺‐ATPase‐based oxygen uptake fractions differ significantly between the two cell types. Nevertheless, no significant differences were found in spontaneous respiration between hPTC and hTALDC. Conclusions: Our results clearly indicate that cell‐specific oxygen consumption parameters have to be considered in the design of biotechnological devices intended to support kidney function by cell‐supported renal replacement therapy. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011     

Hemoglobin/O2 systems: mechanistic discrimination based on Ackers' model

The kinetics of the reaction of hemoglobin with molecular oxygen, in which rapid mixing is followed by a fast temperature jump, is numerically simulated. We use the system of Ackers (1998) which distinguishes four forms of bi-ligated hemoglobin. The data suggest the involvement of isomerization steps for bi- and triliganded hemoglobin. Our first model assumes a linear addition of oxygen with one path to and from each bi-ligated species. Our second model allows cross-overs between paths, as described by Ackers (1998). Our third model exploits the observation (Perrella et al., 1990) that two of the four bi-ligated forms are at low concentration. We explore whether these models can be distinguished experimentally. We find a narrow oxygen concentration range where Models 1 and 2 can be distinguished by rapid flow experiments. The distinction between Models 2 and 3 is larger in stopped flow experiments within a limited oxygen concentration range but not easily detectable in chemical relaxation following rapid flow. The detection of two special states of free hemoglobin may be possible at low oxygen concentration. However, the step reaction free enthalpy (or Gibbs free energy) values make it more likely that two special states are present in fully ligated hemoglobin.     

An experimental and modeling study on the removal of mono-chlorobenzene vapor in biotrickling filters

Removal of mono-chlorobenzene (m-CB) vapor from airstreams was studied in a biotrickling filter (BTF) operating under counter-current flow of the air and liquid streams. Experiments were performed under various values of inlet m-CB concentration, air and/or liquid volumetric flow rates, and pH of the recirculating liquid. Conversion of m-CB was never below 70% and at low concentrations exceeded 90%. A maximum removal rate of about 60 gm-3-reactor h-1 was observed. Conversion of m-CB was found to increase as the values of liquid and air flow rate increase and decrease, respectively. The effects of pH and frequency of medium replenishment on BTF performance were also investigated. The process was successfully described with a detailed mathematical model, which accounts for mass transfer and kinetic effects based on m-CB and oxygen availability. Solution of the model equations yielded m-CB and oxygen concentration profiles in all three phases (airstream, liquid, biofilm). It is predicted that oxygen has a controling effect on the process at high inlet m-CB concentrations. From independent, suspended culture, experiments it was found that m-CB biodegradation follows Andrews inhibitory kinetics. The kinetic constants were found to remain practically unchanged after the culture was used in BTF experiments for 8 months. Copyright 1998 John Wiley & Sons, Inc.     

Blood viscosity and hematological changes during prolonged submergence in normoxic water of northern and southern musk turtles (Sternotherus odoratus)

Musk turtles (Sternotherus odoratus) can survive at least 150 days of submergence in normoxic water at 3 degreesC, during which time there are large increases in packed cell volume (PCV). We investigated the effects of submergence in normoxic water at 3 degreesC on the blood viscosity of musk turtles from northern (Massachusetts) and southern (Alabama) locales. Blood was collected from air-breathing turtles and after 20, 50, 100, and 150 days of submergence in normoxic water at 3 degreesC. Hematological responses to submergence were similar in the two groups, therefore the results were combined. Packed cell volume increased steadily above that of controls after 20, 50, 100, and 150 days of submergence. Hemoglobin concentration also progressively increased above that of controls after 20, 50, and 100 days of submergence but declined to near control values after 150 days. Blood viscosity increased with increasing PCV; however, blood viscosity of musk turtles appears less affected by PCV than is blood viscosity of mammalian species. As such, musk turtles appear to be able to maintain adequate blood flow to tissues while increasing the oxygen carrying capacity of the blood during prolonged submergence. However, after 150 days submergence, oxygen delivery should decrease due to a reduced oxygen carrying capacity of the blood and an increased resistance to blood flow, which may limit the length of time these turtles can remain viable during hibernation.     

Stroma-free hemoglobin: its presence in plasma does not improve oxygen supply to the resting hindlimb vascular bed of hemodiluted dogs.

In hemodilution, red cell spacing in the microcirculation is increased, flow distribution may become more heterogeneous, and, as a result, oxygen supply to tissues may suffer. We tested the hypothesis that oxygen extraction from diluted blood may be enhanced by the presence of hemoglobin in the plasma phase in relatively low concentrations. In anesthetized dogs, the hindlimb vascular bed was isolated and perfused with the animal's own blood by a roller pump. One group of dogs (n = 6) was hemodiluted (hematocrit = 15.0 +/- 1.0%) with a 6% solution of dextran. A second group of dogs (n = 6) was similarly hemodiluted (hematocrit = 16.0 +/- 0.4%) with dextran containing stroma-free hemoglobin solution whereby plasma-phase hemoglobin concentration was raised to 1.1 +/- 0.1 g.dL-1. Systemic hemodynamic observations were made repeatedly over the subsequent 2.5 h, while blood flow to the hindlimb was progressively reduced in stepwise decrements. The hemoglobin-hemodiluted group showed increased systemic arterial blood pressure and total peripheral resistance when compared with the control (dextran diluted) group. The isolated hindlimb also showed evidence of increased vascular resistance in the hemoglobin-treated group. In each individual animal, critical oxygen delivery and extraction were determined by finding the intercept of the supply-independent and supply-dependent portions of the oxygen uptake/oxygen delivery relationship. Neither the critical oxygen delivery rates (5.75 +/- 0.83 vs. 6.41 +/- 0.53 mL.kg-1.min-1) nor critical oxygen extraction ratios (0.75 +/- 0.03 vs. 0.76 +/- 0.04) were found to be significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation of platelet margination phenomena at elevated shear stress

Thrombosis is a common complication following the surgical implantation of blood contacting artificial organs. Platelet transport, which is an important process of thrombosis and strongly modulated by flow dynamics, has not been investigated under the shear stress level associated with these devices, which may range from tens to several hundred Pascal.The current research investigated platelet transport within blood under supra-physiological shear stress conditions through a micro flow visualization approach. Images of platelet-sized fluorescent particles in the blood flow were recorded within microchannels (2 cm x 100 microm x 100 microm). The results successfully demonstrated the occurrence of platelet-sized particle margination under shear stresses up to 193 Pa, revealing a platelet near-wall excess up to 8.7 near the wall (within 15 microm) at the highest shear stress. The concentration of red blood cells was found to influence the stream-wise development of platelet margination which was clearly observed in the 20% Ht sample but not the 40% Ht sample. Shear stress had a less dramatic effect on the margination phenomenon than did hematocrit. The results imply that cell-cell collision is an important factor for platelet transport under supra-physiologic shear stress conditions. It is anticipated that these results will contribute to the future design and optimization of artificial organs.     

Large eddy simulation of the unsteady flow-field in an idealized human mouth-throat configuration

The present study concerns the simulation and analysis of the flow field in the upper human respiratory system in order to gain an improved understanding of the complex flow field with respect to the process affecting drug delivery for medical treatment of the human air system. For this purpose, large eddy simulation (LES) is chosen because of its powerful performance in the transitional range of laminar and turbulent flow fields. The average gas velocity in a constricted tube is compared with experimental data (Ahmed and Giddens, 1983) and numerical data from Reynolds-averaged Navier-Stokes (RANS) equations coupled with low Reynolds number (LRN) κ-ω model (Zhang and Kleinstreuer, 2003) and LRN shear-stress transport κ-ω model (Jayaraju et al., 2007), for model validation. The present study emphasizes on the instantaneous flow field, where the simulations capture different scales of secondary vortices in different flow zones including recirculation zones, the laryngeal jet zone, the mixing zone, and the wall shear layer. It is observed that the laryngeal jet tail breaks up, and the unsteady motion of laryngeal jet is coupled with the unsteady distribution of secondary vortices in the jet boundary. The present results show that it is essential to study the unsteady flow field since it strongly affects the particle flow in the human upper respiratory system associated with drug delivery for medical treatment.     

Dissolved oxygen concentration in river sediment of the Lake Biwa tributaries, Japan

The dissolved oxygen concentration in the sediment pore water downstream of rivers in the Lake Biwa basin was measured, and the factors affecting the dissolved oxygen concentration were analyzed. In August 2003, nine rivers (Sakai, Nakanoi, Hebisuna, Anziki, Yasu, Echi, Ane, Oh, and Ohura) were surveyed. The dissolved oxygen was depleted in the sediment pore water of the rivers with a high proportion of particles less than 250 μm in size. For these rivers, the difference between the dissolved oxygen concentrations of the river surface water and the pore water was large, ranging from −9.54 to −5.26 mg L⁻¹. It was found that the proportion of land turned to paddy fields has an effect on the percentage of the particles below 250 μm (standard partial regression coefficient = 0.807, p = 0.023). These results suggest that, in the Lake Biwa basin, the sedimentation of the fine particles released from paddy fields results in poor dissolved oxygen in the river sediment downstream. In addition, the water flow conditions in small- and medium-scale rivers without headwaters also affect the sedimentation of suspended particles.     

The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters

The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood rheology is not completely investigated. We designed this study to determine the effect of CLTIHH on blood rheology parameters. Present study was performed in 16 male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5 days/week, 5 weeks). The control rats stayed in the same environment as the CLTIHH rats but they breathed room air. In the blood samples aspirated from the heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen concentration, erythrocyte rigidity index and oxygen delivery index were determined. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen concentration values in the CLTIHH group were found to be higher than those of the control group. However, no significant difference was found in erythrocyte rigidity index and oxygen delivery index between the groups. Our results suggested that CLTIHH elevated whole blood viscosity by increasing plasma viscosity, fibrinogen concentration and hematocrit value without effecting the erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high altitude exposure and some severe obstructive sleep apnea (OSA) patients may be responsible for hemorheologic changes in those subjects.     

Mass transfer to fluids flowing through rotating nonaligned straight tubes

Relatively inefficient heat/mass transfer is characteristic of tubular devices if the Reynolds number is low. One method of improving the heat/mass transfer efficiency of such devices is by inducing transverse laminar secondary circulations that are superimposed on the primary flow field; the resulting transverse velocity components lead to fluid mixing and hence augmented mass transfer in the tube lumen. The present work is a theoretical and experimental investigation of the enhanced transport in rotating, nonaligned, straight tubes, a method of transport enhancement that utilizes Coriolis acceleration to create transverse fluid mixing. This technique couples the transport advantages of coiled tubes with the design advantages of straight tubes. The overall mass balance equation is numerically solved for transfer into fluids flowing steadily through rotating nonaligned straight tubes. This solution, for small Coriolis disturbances, incorporates a third order perturbation solution for the primary and secondary flow fields. For sufficiently small Coriolis disturbances the bulk concentration increase is found to be uniquely determined by the value of a single similarity parameter. As the Coriolis disturbance is increased, however, two additional parameters are required to accurately characterize the mass transfer. In general, increasing the Coriolis accelerations results in an increase in mass transfer. There are solution regimens, however, in which increasing this acceleration can lead to a decrease in mass transfer efficiency. This interesting phenomena, which has important design implications, appears to result from velocity-weighting effects on the exiting sample. Experiments, involving the measurement of oxygen transferred into water and blood, produced data that agree with the theoretical predictions.     

Recent developments in ring opening polymerization of lactones for biomedical applications

Aliphatic polyesters prepared by ring-opening polymerization of lactones are now used worldwide as bioresorbable devices in surgery (orthopaedic devices, sutures, stents, tissue engineering, and adhesion barriers) and in pharmacology (control drug delivery). This review presents the various methods of the synthesis of polyesters and tailoring the properties by proper control of molecular weight, composition, and architecture so as to meet the stringent requirements of devices in the medical field. The effect of structure on properties and degradation has been discussed. The applications of these polymers in the biomedical field are described in detail.