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Capillary Blood Cell Velocity in Human Skin Capillaries Located Perpendicularly to the Skin Surface: Measured by a New Laser Doppler Anemometer
... Capillary blood velocity is also obtained by the other methods such as optical flow without using the SIFT method and laser Doppler [24,25]. For example, in a study by Wu et al. [25], the RBC velocity of 12 vessels was examined at three measured locations (arterial, curved, and venous) over 45 seconds of vessel occlusion-flow mode. ...
... The blood velocity in the expressed states obtained from the optical flow method was 79.3 ± 11.7, 84.9 ± 10.9, 53.8 ± 13.9, and 84.8 ± 15.9 μm/s, for rest, obstruction, post-occlusion, and in a release, respectively. In another study [24] using a Doppler laser, the capillary blood velocity of the nailfold area was examined in 20 healthy volunteers (10 men and 10 women). The mean velocity of RBCs within the capillaries was 0.47 ± 0.37 mm/s. ...
Purpose: Measuring the blood flow velocity in capillaries is a useful method for diagnosing many diseases. Despite increasing interest in nailfold capillaroscopy, objective measures of capillary structure and blood flow have been rarely studied. This study aimed to measure the blood flow velocity along the capillary central line using capillaroscopy system, and also ImageJ software used Scale-Invariant Feature Transform (SIFT) tracking algorithms and Kalman filter for image processing.
Materials and Methods: The Red Blood Cells (RBCs) velocity in capillaries of finger nailfold was measured in 12 normal cases using a novel capillaroscopy system. The measurements of the velocity were performed at 12 points in nailfold regions by two observers separately. The image processing and automated measurement take 1-2 min per nailfold. FFmpeg software was used to convert the images format, and then the images were imported to ImageJ software and segmented. SIFT tracking algorithms and Kalman filter were used to filter noise and irregularities in the images. For reproducibility, the velocity distribution values obtained by the two performers, and Paired T-Test was used. The reliability of a measuring instrument or calculation method depends on the tools obtained using Cronbach's alpha. To assess the repeatability of the algorithm, the capillary velocity values were executed at different times with 24-hour intervals using a coefficient of variance method.
Results: The calculated RBCs velocity was in the range of 0.05-0.16 mm/s. The results based on Cronbach's alpha analysis for reliability factor was 0.97, with a good correlation among the measurements, 0.85. The average velocity (along with standard deviation) for repeatability at three different times was obtained 0.1195 ± 0.0246, 0.0974 ± 0.0221, and 0.0962 ± 0.0202 mm/s, demonstrating that there was no statistically variation between these measurements (P-value > 0.05). The velocity results for the two observers were 0.811 ± 0.392 and 0.819 ± 0.325 mm/s, indicating a good reproducibility between them (P-value = 0.959).
Conclusion: For the measurements of nailfold capillaries velocity, there was good/reasonable reliability, repeatability, and reproducibility. The results indicated a good accuracy of capillaroscopy system and ImageJ software with SIFT algorithm and Kalman filter, which can be used as an appropriate tool for determining the rate of nailfold blood flow velocity.
... Skin blood flow velocity (v). Mean values for skin blood flow velocity (SkBV) have been reported to be between 0.4 and 0.6 cm/s with a total range observed from 0.1 cm/s to 0.9 cm/s in nonheated skin with a mean temperature of 32-34 C (28). In patients with shock, the average decrease in SkBV, as measured with laser doppler, ranges from 60% to 95% when compared with healthy human volunteers (52). ...
Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel non-invasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPO2). As the most downstream marker of oxygen balance in the skin, mitoPO2 may provide additional information to improve shock management. However, a physiological basis for the interpretation of mitoPO2 values has not been established yet. In this paper we developed a mathematical model of skin mitoPO2 using a network of parallel microvessels, based on Krogh's cylinder model. The model contains skin blood flow velocity, heterogeneity of blood flow, hematocrit, arteriolar oxygen saturation and mitochondrial oxygen consumption as major variables. The major results of the model show that normal physiological mitoPO2 is in the range of 40-60mmHg. The relationship of mitoPO2 with skin blood flow velocity follows a hyperbolic curve, reaching a plateau at high skin blood flow velocity, suggesting that oxygen balance remains stable whilst peripheral perfusion declines. The model shows that a critical range exists where mitoPO2 rapidly deteriorates if skin perfusion further decreases. The model intuitively shows how tissue hypoxia could occur in the setting of septic shock, due to the profound impact of microcirculatory disturbance on mitoPO2, even at sustained cardiac output. MitoPO2 is the result of a complex interaction between all factors of oxygen delivery and the microcirculation. This mathematical framework can be used to interpret mitoPO2 values in shock, with the potential to enhance personalized clinical trial design.
... The mesh lines are designed to be thin (~2 μm-wide), so they function as a wedge between cells, forcing cluster cells into different openings and arresting the cluster at cell-cell junctions. To guard against cluster dissociation by mesh lines, cell flow speed was set as low as 65 μm/s ( Supplementary Fig. 1),~10× lower than physiological free flow speed in human capillaries 29 . To maintain gentle handling of CTC clusters while still achieving clinically relevant throughput rates, we operated a large number of cluster-trapping wells in parallel. ...
Extremely rare circulating tumor cell (CTC) clusters are both increasingly appreciated as highly metastatic precursors and virtually unexplored. Technologies are primarily designed to detect single CTCs and often fail to account for the fragility of clusters or to leverage cluster-specific markers for higher sensitivity. Meanwhile, the few technologies targeting CTC clusters lack scalability. Here, we introduce the Cluster-Wells, which combines the speed and practicality of membrane filtration with the sensitive and deterministic screening afforded by microfluidic chips. The >100,000 microwells in the Cluster-Wells physically arrest CTC clusters in unprocessed whole blood, gently isolating virtually all clusters at a throughput of >25 mL/h, and allow viable clusters to be retrieved from the device. Using the Cluster-Wells, we isolated CTC clusters ranging from 2 to 100+ cells from prostate and ovarian cancer patients and analyzed a subset using RNA sequencing. Routine isolation of CTC clusters will democratize research on their utility in managing cancer.
... We selected these flow rates as they coincide with a blood flow rate in wound sites ranging from 50 to 110 µL/ min for 1 g tissue. The resting capillary blood flow velocity is reported to be ~ 0.65 mm 3 /s at skin temperature of 30.4 °C, corresponding to 0.04 mL/min (Stücker et al. 1996). The computational calculation was based on the Navier-Stokes equations, and due to the very low Reynolds number in microfluidic devices, the inertial component was neglected, allowing a higher mesh density for computation. ...
Microbial biofilms are composed of surface-adhered microorganisms enclosed in extracellular polymeric substances. The biofilm lifestyle is the intrinsic drug resistance imparted to bacterial cells protected by the matrix. So far, conventional drug susceptibility tests for biofilm are reagent and time-consuming, and most of them are in static conditions. Rapid and easy-to-use methods for biofilm formation and antibiotic activity testing need to be developed to accelerate the discovery of new antibiofilm strategies. Herein, a Lab-On-Chip (LOC) device is presented that provides optimal microenvironmental conditions closely mimicking real-life clinical biofilm status. This new device allows homogeneous attachment and immobilization of Pseudomonas aeruginosa PA01-EGFP cells, and the biofilms grown can be monitored by fluorescence microscopy. P. aeruginosa is an opportunistic pathogen known as a model for drug screening biofilm studies. The influence of flow rates on biofilms growth was analyzed by flow simulations using COMSOL® 5.2. Significant cell adhesion to the substrate and biofilm formation inside the microchannels were observed at higher flow rates > 100 µL/h. After biofilm formation, the effectiveness of silver nanoparticles (SNP), chitosan nanoparticles (CNP), and a complex of chitosan-coated silver nanoparticles (CSNP) to eradicate the biofilm under a continuous flow was explored. The most significant loss of biofilm was seen with CSNP with a 65.5% decrease in average live/dead cell signal in biofilm compared to the negative controls. Our results demonstrate that this system is a user-friendly tool for antibiofilm drug screening that could be simply applied in clinical laboratories.
Key Points
• A continuous-flow microreactor that mimics real-life clinical biofilm infections was developed.• The antibiofilm activity of three nano drugs was evaluated in dynamic conditions.• The highest biofilm reduction was observed with chitosan-silver nanoparticles.Graphical abstract
... An additional complexity to consider, in order to assess the relevance of our results to live subjects, is that live skin is continuously blood-irrigated, which is a source for heat transport (advection) not at play in our experiments. In the skin capillaries, which are likely present locally around any rupture, an order of magnitude for the blood velocity at rest is V B ∼ 0.5 mm s -1 (e.g., [64]). Even considering a perfect and instantaneous heat transfer between the structural tissue and such a blood network (a hardly realistic hypothesis), this would imply a smear of the dissipated heat over, at most, a distance τ V B ∼ 10 µm, for the time interval τ = 20 ms accessible to our camera. ...
Mechanical pain (or mechanical algesia) can both be a vital mechanism warning us for dangers or an undesired medical symptom important to mitigate. Thus, a comprehensive understanding of the different mechanisms responsible for this type of pain is paramount. In this work, we study the tearing of porcine skin in front of an infrared camera, and show that mechanical injuries in biological tissues can generate enough heat to stimulate the neural network. In particular, we report local temperature elevations of up to 24°C around fast cutaneous ruptures, which shall exceed the threshold of the neural nociceptors usually involved in thermal pain. Slower fractures exhibit lower temperature elevations, and we characterise such dependency to the damaging rate. Overall, we bring experimental evidence of a novel—thermal—pathway for direct mechanical algesia. In addition, the implications of this pathway are discussed for mechanical hyperalgesia, in which a role of the cutaneous thermal sensors has priorly been suspected. We also show that thermal dissipation shall actually account for a significant portion of the total skin's fracture energy, making temperature monitoring an efficient way to detect biological damages.
... We focus on capillaries, arterioles, and arteries because they transport drugs to the tumor site, whereas venules and veins transport drugs away from the tumor site, making them ineffective for drug delivery. We use experimentally found constants for the maximum blood velocity and vessel radii in humans: R = 4 × 10 −6 m and u max = 9.3 × 10 −4 m/s in capillaries, R = 1.5×10 −5 m and u max = 3.26×10 −3 m/s in arterioles, and R = 2 × 10 −3 m and u max = 0.19 m/s in arteries [26][27][28][29]. ...
A numerical model is developed for the motion of superparamagnetic nanoparticles in a non-Newtonian blood flow under the influence of a magnetic field. The rheological properties of blood are modeled by the Carreau flow and viscosity, and the stochastic effects of Brownian motion and red blood cell collisions are considered. The model is validated with existing data and good agreement with experimental results is shown. The effectiveness of magnetic drug delivery in various blood vessels is assessed and found to be most successful in arterioles and capillaries. A range of magnetic field strengths are modeled using equations for both a bar magnet and a point dipole: it is shown that the bar magnet is effective at capturing nanoparticles in limited cases while the point dipole is highly effective across a range of conditions. A parameter study is conducted to show the effects of changing the dipole moment, the distance from the magnet to the blood vessel, and the initial release point of the nanoparticles. The distance from the magnet to the blood vessel is shown to play a significant role in determining nanoparticle capture rate. The optimal initial release position is found to be located within the tumor radius in capillaries and arterioles to prevent rapid diffusion to the edges of the blood vessel prior to arriving at the tumor, and near the edge of the magnet when a bar magnet is used.
Magnetically-actuated microrobots (MARs) exhibit great potential in biomedicine owing to their precise navigation, wireless actuation and remote operation in confined space. However, most previously explored MARs unfold the drawback of...
Assessment of blood perfusion from superficial layers would aid in monitoring the microcirculation and help diagnose numerous diseases involving altered microcirculation. Diffuse optical correlation spectroscopy looks at the correlation between temporal statistics of backscattered intensity from tissue surface upon illumination and has been a promising tool for tissue vascularity assessment. This work uses diffuse correlation spectroscopy operated in short source-to-detector separation to quantify microcirculation. Finite element models and simulations are validated with in-vitro skin flow models. The comparison returned a high correlation between the simulation and experimental models, proving short-range DCS's capability in assessing microcirculation
A numerical model is developed for the motion of superparamagnetic nanoparticles in a non-Newtonian blood flow under the influence of a magnetic field. The rheological properties of blood are modeled by the Carreau flow and viscosity, and the stochastic effects of Brownian motion and red blood cell collisions are considered. The model is validated with existing data and good agreement with experimental results is shown. The effectiveness of magnetic drug delivery in various blood vessels is assessed and found to be most successful in arterioles and capillaries. A range of magnetic field strengths are modeled using equations for both a bar magnet and a point dipole: it is shown that the bar magnet is effective at capturing nanoparticles in limited cases, while the point dipole is highly effective across a range of conditions. A parameter study is conducted to show the effects of changing the dipole moment, the distance from the magnet to the blood vessel, and the initial release point of the nanoparticles. The distance from the magnet to the blood vessel is shown to play a significant role in determining nanoparticle capture rate. The optimal initial release position is found to be located within the tumor radius in capillaries and arterioles to prevent rapid diffusion to the edges of the blood vessel prior to arriving at the tumor and near the edge of the magnet when a bar magnet is used.
Transdermal delivery is a recent phenomenon in terms of smart drug delivery. Diabetes has been one of the leading causes of death throughout the world. Besides death, diabetic patients need to take regular doses of insulin for maintaining normoglycemic conditions. Transdermal patches can be limited in their efficacy for delivering insulin as it has a high molecular weight. Personalization of insulin delivery patches can result in optimal drug delivery, varying anatomical position, and controlling insulin uptake within the body. The objective of this work was to quantify the change in insulin concentration while using a transdermal insulin patch with multiple microneedles along with convectional blood flow. To this end, COMSOL has been used for insulin concentration simulation at multiple locations of the body and at different skin positions. It has been found, shoulder and forearm are the suitable locations for bolus insulin delivery while the abdomen is better suited for basal insulin delivery. The simulation showed a 66% difference in insulin concentration at blood flow between shoulder and abdomen location. This work can improve our understanding of insulin patch placement and thus transdermal therapy. Here, the validated model can work as a great starting block for further simulation including glucose control simulations.
A laser Doppler technique which provides a means of obtaining absolute measurements of the speed of red blood cells (RBCs) flowing in individual retinal vessels is described. Doppler-shift frequency spectra of laser light scattered from the RBCs are obtained for two directions of the scattered light. Each spectrum exhibits a cutoff frequency that is directly related to the maximum RBC speed (Vmax). The difference in cutoff frequencies is used to obtain an absolute measure of Vmax that is independent of the exact orientation of the vessel and of the relative direction of the incident and scattered beams with respect to the flow direction. Preliminary measurements obtained using a prototype instrument are presented.
The flow velocity profile in the venule of frog web was measured by using a laser Doppler microscope of a crossed-beam which permitted a measurement of flow velocity in a clearly defined small volume. The flow velocity profile in the venule seems to deviate slightly from the Newtonian parabola.
Proefschrift Maastricht. Lit.opg. - Samenvatting in het Nederlands.
A noninvasive technique for studying blood flow dynamics in human skin capillaries is described. A light microscope combined with a closed-circuit TV system was used to monitor and record capillary blood flow velocity on video tape. Arterial pulsations were recorded plethysmographically and converted into video signals by modulating the position of a square, white area in the televised scene. Twelve healthy subjects were studied. The mean (+/- SD) resting capillary blood flow velocity was 0.65 +/- 0.3 mm/s at an average skin temperature of 30.4 +/- 2.3 degrees C. Spontaneous fluctuations at a frequency of 6-10 cycles/min were observed in most subjects. A well-pronounced flow pulsatile component could be demonstrated in all capillaries studied. The technique can be used in clinical practice for studying the physiology and pathophysiology of cutaneous microcirculation in man. It can be expected that the method may become an important diagnostic tool in diseases that involve disturbances of the microcirculation, such as diabetes, hypertension, and atherosclerosis.
The speed of red blood cells in the capillaries of the human nailfold was evaluated noninvasively with the aid of a television microscope and by analyzing the video data in three different ways: (1) By a frame-to-frame determination of the position of a plasma gap in the capillary; (2) By using a two-channel video densitometer which provided signals proportional to the average light level in two windows positioned at an upstream and a downstream site of the televised capillary. The time delay between similar characteristic features in the recorded upstream and downstream signals produced by the passage of plasma gaps and erythrocytes was measured manually; (3) By a direct on-line cross-correlation of the densitometer signals from the upstream and downstream windows. All three methods were found to yield average values well within the experimental error of the techniques, which is estimated to be on the order of 0.1 mm/sec. Frame-by-frame analysis and time delay determinations from densitometer signals produced compatible results for both, speed fluctuations and average speed. Direct online cross-correlation yielded a lower estimate of fluctuations because of the inherent averaging properties of the method. This inaccuracy, however, is compensated by the increased speed of data reduction.
Blood flow analysis in the microcirculation requires accurate measurement of velocity, volume flow and shear-rate versus shear-stress relationships. The resolution of most anemometers is too limited to obtain useful measurements, especially near the blood vessel wall and at branches and bifurcations. To make such measurements possible with a noninvasive, high resolution, accurate technique, we have developed a fringe mode, transmittance laser Doppler microscope anemometer (LDMA). This system has an intrinsically high spatial resolution (10 x 12 microns), and does not require a high concentration (10(6)/cm3) of scatters or red blood cells (RBC) as in our application. Preliminary measurements of water flow in a rectangular channel were conducted to ascertain the reliability and accuracy of velocity measurements using the LDMA. Velocity profiles were then measured by the LDMA system in arterioles 38-135 microns in diameter, in the transparent, everted cheek pouch of the anaesthetized hamster. The extremely high resolution of the optical system, and the ultra-fine traversing mechanism of the microscope stage, made velocity readings larger than 0.02 mm/s with accuracy and reproducibility better than 1%, possible near the wall to within 7-10 microns.
The success of measuring red cell velocity in microvessels by television methods based on cross-correlation depends to a considerable extent on the optical contrast between red cells and plasma gaps passing through these vessels. Poor optical contrast, such as under conditions of low magnification, may result in deteriorated cross-correlograms and, consequently, in completely erroneous velocity values. The success of measuring velocity by the flying spot technique, however, depends only on the operator's ability (1) to discern the moving red cells, and (2) to match the speed of the spot to that of these cells. We have implemented this technique as a television method and estimated the subjective error involved in this velocity matching. Under a total magnification of 112 X, the estimated relative errors among four observers in the velocity range from 0.10 to 0.57 mm/s varied between 4.4 and 14.9%, while the overall error was 8.7%. It was concluded that this technique can provide, in the range from 0 up to possibly 1-2 mm/s, quick and reliable velocity measurements with a reasonable accuracy. Also, since no sophisticated equipment is required for the implementation, this method, at present, is much less expensive than the other conventional television methods for measuring velocity.
Measurement of velocity profiles in simulated blood flow by the laser-Doppler technique. Paper 4-2-95, Symposium on Flow—Its Measurement and Control in Science and Industry Skin capillary blood cell velocity in man. Characteristics and reproduc-ibility of the reactive hyperemia response
- D Kreid
- R Goldstein
- Pittsburgh
- J O ¨ Stergren
- B Fagrell
Kreid, D., and Goldstein, R. (1971). Measurement of velocity profiles in simulated blood flow by the laser-Doppler technique. Paper 4-2-95, Symposium on Flow—Its Measurement and Control in Science and Industry. Pittsburgh. O ¨ stergren, J., and Fagrell, B. (1986). Skin capillary blood cell velocity in man. Characteristics and reproduc-ibility of the reactive hyperemia response. Int. J. Microcirc. Clin. Exp. 5, 37–51.