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1.
The India-Asia collision is an outstanding smoking gun in the study of continental collision dynamics. How and when the continental collision occurred remains a long-standing controversy. Here we present two new paleomagnetic data sets from rocks deposited on the distal part of the Indian passive margin, which indicate that the Tethyan Himalaya terrane was situated at a paleolatitude of ∼19.4°S at ∼75 Ma and moved rapidly northward to reach a paleolatitude of ∼13.7°N at ∼61 Ma. This implies that the Tethyan Himalaya terrane rifted from India after ∼75 Ma, generating the North India Sea. We document a new two-stage continental collision, first at ∼61 Ma between the Lhasa and Tethyan Himalaya terranes, and subsequently at ∼53−48 Ma between the Tethyan Himalaya terrane and India, diachronously closing the North India Sea from west to east. Our scenario matches the history of India-Asia convergence rates and reconciles multiple lines of geologic evidence for the collision.  相似文献   

2.
In this paper, we present an on-chip hand-powered membrane pump using a robust patient-to-chip syringe interface. This approach enables safe sample collection, sample containment, integrated sharps disposal, high sample volume capacity, and controlled downstream flow with no electrical power requirements. Sample is manually injected into the device via a syringe and needle. The membrane pump inflates upon injection and subsequently deflates, delivering fluid to downstream components in a controlled manner. The device is fabricated from poly(methyl methacrylate) (PMMA) and silicone, using CO2 laser micromachining, with a total material cost of ∼0.20 USD/device. We experimentally demonstrate pump performance for both deionized (DI) water and undiluted, anticoagulated mouse whole blood, and characterize the behavior with reference to a resistor-capacitor electrical circuit analogy. Downstream output of the membrane pump is regulated, and scaled, by connecting multiple pumps in parallel. In contrast to existing on-chip pumping mechanisms that typically have low volume capacity (∼5 μL) and sample volume throughput (∼1–10 μl/min), the membrane pump offers high volume capacity (up to 240 μl) and sample volume throughput (up to 125 μl/min).  相似文献   

3.
We present an optofluidic microvalve utilizing an embedded, surface plasmon-enhanced fiber optic microheater. The fiber optic microheater is formed by depositing a titanium thin film on the roughened end-face of a silica optical fiber that serves as a waveguide to deliver laser light to the titanium film. The nanoscale roughness at the titanium-silica interface enables strong light absorption enhancement in the titanium film through excitation of localized surface plasmons as well as facilitates bubble nucleation. Our experimental results show that due to the unique design of the fiber optic heater, the threshold laser power required to generate a bubble is greatly reduced and the bubble growth rate is significantly increased. By using the microvalve, stable vapor bubble generation in the microchannel is demonstrated, which does not require complex optical focusing and alignment. The generated vapor bubble is shown to successfully block a liquid flow channel with a size of 125 μm × 125 μm and a flow rate of ∼10 μl/min at ∼120 mW laser power.  相似文献   

4.
HbA1c is used extensively for the diagnosis and management of diabetes mellitus. It constitutes 80% of glycated HbA1(Glycated haemoglobin(GHb)A), and depends upon blood glucose and RBC life span. RBC life span varies with anemia, leading to a consequent alteration in the HbA1c value irrespective of the circulating blood glucose concentration. But to the best of our knowledge no Hb cut offs have been derived for appropriate interpretation of HbA1c. The prevalence of anemia in Indian population is nearly 40% as per its definition by WHO—Hb < 12 g/dL in females and < 13 g/dL in males—with most cases attributable to nutritional deficiencies. Hence, we aimed to identify Hb cut-off for accurate interpretation of HbA1c in presence of deficiency anemias. Partial correlation between random blood glucose (RBG) and HbA1c was studied in 1312 subjects, 470 of whom had deficiency-related anemia]. The data was adjusted for age, sex and Hb. Partial correlation between RBG and HbA1c was highly significant (p < 0.0001) till Hb of 8.1 gm/dL. Significance reduced to p = 0.003 and p = 0.006 as the cut off of Hb reduced to 7.1 gm/dL and 5.0 gm/dL, respectively, but was not lost. Hence, caution in interpretation of HbA1c is not required till an Hb of 5 g/dL.  相似文献   

5.
Alternating current (AC) dielectrophoresis (DEP) experiments for biological particles in microdevices are typically done at a fixed frequency. Reconstructing the DEP response curve from static frequency experiments is laborious, but essential to ascertain differences in dielectric properties of biological particles. Our lab explored the concept of sweeping the frequency as a function of time to rapidly determine the DEP response curve from fewer experiments. For the purpose of determining an ideal sweep rate, homogeneous 6.08 μm polystyrene (PS) beads were used as a model system. Translatability of the sweep rate approach to ∼7 μm red blood cells (RBC) was then verified. An Au/Ti quadrapole electrode microfluidic device was used to separately subject particles and cells to 10Vpp AC electric fields at frequencies ranging from 0.010 to 2.0 MHz over sweep rates from 0.00080 to 0.17 MHz/s. PS beads exhibited negative DEP assembly over the frequencies explored due to Maxwell-Wagner interfacial polarizations. Results demonstrate that frequency sweep rates must be slower than particle polarization timescales to achieve reliable incremental polarizations; sweep rates near 0.00080 MHz/s yielded DEP behaviors very consistent with static frequency DEP responses for both PS beads and RBCs.  相似文献   

6.
In this report, we demonstrate a simple and low cost method that can be reproducibly used for fabrication of microfluidic devices in nitrocellulose. The fluidic patterns are created via a laser-based direct-write technique that induces polymerisation of a photo-polymer previously impregnated in the nitrocellulose. The resulting structures form hydrophobic barriers that extend through the thickness of the nitrocellulose and define an interconnected hydrophilic fluidic-flow pattern. Our experimental results show that using this method it is possible to achieve microfluidic channels with lateral dimensions of ∼100 μm using hydrophobic barriers that form the channel walls with dimensions of ∼60 μm; both of these values are considerably smaller than those that can be achieved with other current techniques used in the fabrication of nitrocellulose-based fluidic devices. A simple grid patterned nitrocellulose device was then used for the detection of C-reactive protein via a sandwich enzyme-linked immunosorbent assay, which served as a useful proof-of-principle experiment.  相似文献   

7.
This study suggests a new erythrocyte sedimentation rate (ESR) measurement method for the biophysical assessment of blood by using a microfluidic device. For an effective ESR measurement, a disposable syringe filled with blood is turned upside down and aligned at 180° with respect to gravitational direction. When the blood sample is delivered into the microfluidic device from the top position of the syringe, the hematocrit of blood flowing in the microfluidic channel decreases because the red blood cell-depleted region is increased from the top region of the syringe. The variation of hematocrit is evaluated by consecutively capturing images and conducting digital image processing technique for 10 min. The dynamic variation of ESR is quantitatively evaluated using two representative parameters, namely, time constant (λ) and ESR-area (AESR). To check the performance of the proposed method, blood samples with various ESR values are prepared by adding different concentrations of dextran solution. λ and AESR are quantitatively evaluated by using the proposed method and a conventional method, respectively. The proposed method can be used to measure ESR with superior reliability, compared with the conventional method. The proposed method can also be used to quantify ESR of blood collected from malaria-infected mouse under in vivo condition. To indirectly compare with the results obtained by the proposed method, the viscosity and velocity of the blood are measured using the microfluidic device. As a result, the biophysical properties, including ESR and viscosity of blood, are significantly influenced by the parasitemia level. These experimental demonstrations support the notion that the proposed method is capable of effectively monitoring the biophysical properties of blood.  相似文献   

8.
The authors exposed a non-equilibrium dynamic counterion and coion analyte concentration to an AC electric field to selectively concentrate peptides at the poles of a cation-selective granule. The counterion polarization results from the focusing of the electric field show a discontinuous drop in the intra-granule counterion electromigration flux at the pole. The coion concentration polarization is due to the combined external convective and electromigration fluxes toward the pole that neutralize the accumulating counterions. Because the electromigration mobility of the peptide anion analyte depends on the pH, the authors determined a 20 000-fold high concentration factor for a near-neutral pH of 6.0 to 7.7. Because the peptide is protonated at the acidic pole and its absolute charge ranges from −0.3 to −1.9, the concentration factor scales exponentially with the absolute charge, thus allowing extremely selective concentrations of various peptides, which is demonstrated by fluorescein isothiocyanate tagged angiotensin I (pI ∼ 5.8) and Texas red tagged avidin (pI ∼ 10.5). This dynamic concentration effect can substantially enhance the sensitivity of bio-assays.  相似文献   

9.
Blood cell sorting is critical to sample preparation for both clinical diagnosis and therapeutic research. The spiral inertial microfluidic devices can achieve label-free, continuous separation of cell mixtures with high throughput and efficiency. The devices utilize hydrodynamic forces acting on cells within laminar flow, coupled with rotational Dean drag due to curvilinear microchannel geometry. Here, we report on optimized Archimedean spiral devices to achieve cell separation in less than 8 cm of downstream focusing length. These improved devices are small in size (<1 in.2), exhibit high separation efficiency (∼95%), and high throughput with rates up to 1 × 106 cells per minute. These device concepts offer a path towards possible development of a lab-on-chip for point-of-care blood analysis with high efficiency, low cost, and reduced analysis time.  相似文献   

10.
Wei Hou H  Gan HY  Bhagat AA  Li LD  Lim CT  Han J 《Biomicrofluidics》2012,6(2):24115-2411513
Sepsis is an adverse systemic inflammatory response caused by microbial infection in blood. This paper reports a simple microfluidic approach for intrinsic, non-specific removal of both microbes and inflammatory cellular components (platelets and leukocytes) from whole blood, inspired by the invivo phenomenon of leukocyte margination. As blood flows through a narrow microchannel (20 × 20 µm), deformable red blood cells (RBCs) migrate axially to the channel centre, resulting in margination of other cell types (bacteria, platelets, and leukocytes) towards the channel sides. By using a simple cascaded channel design, the blood samples undergo a 2-stage bacteria removal in a single pass through the device, thereby allowing higher bacterial removal efficiency. As an application for sepsis treatment, we demonstrated separation of Escherichia coli and Saccharomyces cerevisiae spiked into whole blood, achieving high removal efficiencies of ∼80% and ∼90%, respectively. Inflammatory cellular components were also depleted by >80% in the filtered blood samples which could help to modulate the host inflammatory response and potentially serve as a blood cleansing method for sepsis treatment. The developed technique offers significant advantages including high throughput (∼1 ml/h per channel) and label-free separation which allows non-specific removal of any blood-borne pathogens (bacteria and fungi). The continuous processing and collection mode could potentially enable the return of filtered blood back to the patient directly, similar to a simple and complete dialysis circuit setup. Lastly, we designed and tested a larger filtration device consisting of 6 channels in parallel (∼6 ml/h) and obtained similar filtration performances. Further multiplexing is possible by increasing channel parallelization or device stacking to achieve higher throughput comparable to convectional blood dialysis systems used in clinical settings.  相似文献   

11.
A novel microfluidic device which consists of two stages for particle focusing and separation using a viscoelastic fluid has been developed. A circular capillary tube was used for three-dimensional particle pre-alignment before the separation process, which was inserted in a polydimethylsiloxane microchannel. Particles with diameters of 5 and 10 μm were focused at the centerline in the capillary tube, and the location of particles was initialized at the first bifurcation. Then, 5 and 10 μm particles were successfully separated in the expansion region based on size-dependent lateral migration, with ∼99% separation efficiency. The proposed device was further applied to separation of MCF-7 cells from leukocytes. Based on the cell size distribution, an approximate size cutoff for separation was determined to be 16 μm. At 200 μl/min, 94% of MCF-7 cells were separated with the purity of ∼97%. According to the trypan blue exclusion assay, high viability (∼90%) could be achieved for the separated MCF-7 cells. The use of a commercially available capillary tube enables the device to be highly versatile in dealing with particles in a wide size range by using capillary tubes with different inner diameters.  相似文献   

12.
Cytokines are small proteins secreted by leukocytes in blood in response to infections, thus offering valuable diagnostic information. Given that the same cytokines may be produced by different leukocyte subsets in blood, it is beneficial to connect production of cytokines to specific cell types. In this paper, we describe integration of antibody (Ab) microarrays into a microfluidic device to enable enhanced cytokine detection. The Ab arrays contain spots specific to cell-surface antigens as well as anti-cytokine detection spots. Infusion of blood into a microfluidic device results in the capture of specific leukocytes (CD4 T-cells) and is followed by detection of secreted cytokines on the neighboring Ab spots using sandwich immunoassay. The enhancement of cytokine signal comes from leveraging the concept of reconfigurable microfluidics. A three layer polydimethylsiloxane microfluidic device is fabricated so as to contain six microchambers (1 mm × 1 mm × 30 μm) in the ceiling of the device. Once the T-cell capture is complete, the device is reconfigured by withdrawing liquid from the channel, causing the chambers to collapse onto Ab arrays and enclose cell/anti-cytokine spots within a 30 nl volume. In a set of proof-of-concept experiments, we demonstrate that ∼90% pure CD4 T-cells can be captured inside the device and that signals for three important T-cell secreted cytokines, tissue necrosis factor-alpha, interferon-gamma, and interleukin-2, may be enhanced by 2 to 3 folds through the use of reconfigurable microfluidics.  相似文献   

13.
We present an engineered three-dimensional (3D) in vitro brain microvasculature system embedded within the bulk of a collagen matrix. To create a hydrogel template for the functional brain microvascular structure, we fabricated an array of microchannels made of collagen I using microneedles and a 3D printed frame. By culturing mouse brain endothelial cells (bEnd.3) on the luminal surface of cylindrical collagen microchannels, we reconstructed an array of brain microvasculature in vitro with circular cross-sections. We characterized the barrier function of our brain microvasculature by measuring transendothelial permeability of 40 kDa fluorescein isothiocyanate-dextran (Stoke''s radius of ∼4.5 nm), based on an analytical model. The transendothelial permeability decreased significantly over 3 weeks of culture. We also present the disruption of the barrier function with a hyperosmotic mannitol as well as a subsequent recovery over 4 days. Our brain microvasculature model in vitro, consisting of system-in-hydrogel combined with the widely emerging 3D printing technique, can serve as a useful tool not only for fundamental studies associated with blood-brain barrier in physiological and pathological settings but also for pharmaceutical applications.  相似文献   

14.
The flow of λ-DNA solutions in a gradual micro-contraction was investigated using direct measurement techniques. The effects on DNA transport in microscale flows are significant because the flow behavior is influenced by macromolecular conformations, both viscous and elastic forces dominate inertial forces at this length scale, and the fully extended length of the molecule approaches the characteristic channel length wc (L/wc ∼ 0.13). This study examines the flow of semi-dilute and entangled DNA solutions in a gradual planar micro-contraction for low Reynolds numbers (3.7 × 10−6 < Re < 3.1 × 10−1) and high Weissenberg numbers (0.4 < Wi < 446). The semi-dilute DNA solutions have modest elasticity number, El = Wi/Re = 55, and do not exhibit viscoelastic behavior. For the entangled DNA solutions, we access high elasticity numbers (7.9 × 103 < El < 6.0 × 105). Video microscopy and streak images of entangled DNA solution flow reveal highly elastic behavior evidenced by the presence of large, stable vortices symmetric about the centerline and upstream of the channel entrance. Micro-particle image velocimetry measurements are used to obtain high resolution, quantitative velocity measurements of the vortex growth in this micro-contraction flow. These direct measurements provide a deeper understanding of the underlying physics of macromolecular transport in microfluidic flow, which will enable the realization of enhanced designs of lab-on-a-chip systems.  相似文献   

15.

Background

The preanalytical phase represents the major source of variability in laboratory diagnostics. Our aim was to assess to what extent underfilling of primary blood tubes may impact upon routine coagulation testing.

Materials and methods:

Blood was drawn by syringe from 21 healthy volunteers and 6 patients on warfarin therapy, and immediately transferred into 3.6 mL vacuum tubes containing 3.2% sodium citrate (Terumo Europe N.V., Leuven, Belgium). All tubes were filled using standardized volumes of whole blood to produce scalar amounts of filling: 3.6 mL (i.e., 100%), 3.2 mL (89%), 2.8 mL (78%) and 2.4 mL (67%). Samples were mixed and centrifuged at 1300 × g for 10 min. The plasma was tested for prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FBG) on ACL TOP (Instrumentation Laboratory - IL, Milan, Italy), using IL reagents. A polynomial plot was derived for each parameter from interpolation of clotting values obtained with different percentages of filling, and these plots were compared with quality specifications (± 2.0 for PT, ± 2.3 for APTT and ± 4.8 for FBG) to calculate the minimal filling volume required to produce clinically acceptable results.

Results:

The equations were (PF, Percentage of filling): PT (sec) = 3.375 × PF^2–6.255 × PF + 17.806 (r = 0.980); APTT (sec) = 8.925 × PF^2–23.578 × PF + 46.356 (r = 0.979); and FBG (mg/dL) = −311.5 × PF^2 + 422.1 × PF + 147.07 (r = 0.994). According to these equations, the minimum allowed thresholds of blood tubes filling were > 61% for PT, > 87% for APTT and > 71% for FBG.

Conclusions:

Our results confirm that routine coagulation testing performed on underfilled tubes may generate biased and clinically misleading test results. This is particularly critical for APTT, wherein tubes filled at less than ∼90% generate unreliable data. The FBG and the PT seem more resistant to underfilling, clinical significant biases being observed only where blood tubes were filled at less than ∼60 and ∼70%, respectively.  相似文献   

16.
We present a method capable of rapidly (∼20 s) determining the density and mass of a single leukemic cell using an optically induced electrokinetics (OEK) platform. Our team had reported recently on a technique that combines sedimentation theory, computer vision, and micro particle manipulation techniques on an OEK microfluidic platform to determine the mass and density of micron-scale entities in a fluidic medium; the mass and density of yeast cells were accurately determined in that prior work. In the work reported in this paper, we further refined the technique by performing significantly more experiments to determine a universal correction factor to Stokes'' equation in expressing the drag force on a microparticle as it falls towards an infinite plane. Specifically, a theoretical model for micron-sized spheres settling towards an infinite plane in a microfluidic environment is presented, and which was validated experimentally using five different sizes of micro polystyrene beads. The same sedimentation process was applied to two kinds of leukemic cancer cells with similar sizes in an OEK platform, and their density and mass were determined accordingly. Our tests on mouse lymphocytic leukemia cells (L1210) and human leukemic cells (HL-60) have verified the practical viability of this method. Potentially, this new method provides a new way of measuring the volume, density, and mass of a single cell in an accurate, selective, and repeatable manner.  相似文献   

17.
Measuring forces applied by multi-cellular organisms is valuable in investigating biomechanics of their locomotion. Several technologies have been developed to measure such forces, for example, strain gauges, micro-machined sensors, and calibrated cantilevers. We introduce an innovative combination of techniques as a high throughput screening tool to assess forces applied by multiple genetic model organisms. First, we fabricated colored Polydimethylsiloxane (PDMS) micropillars where the color enhances contrast making it easier to detect and track pillar displacement driven by the organism. Second, we developed a semi-automated graphical user interface to analyze the images for pillar displacement, thus reducing the analysis time for each animal to minutes. The addition of color reduced the Young''s modulus of PDMS. Therefore, the dye-PDMS composite was characterized using Yeoh''s hyperelastic model and the pillars were calibrated using a silicon based force sensor. We used our device to measure forces exerted by wild type and mutant Caenorhabditis elegans moving on an agarose surface. Wild type C. elegans exert an average force of ∼1 μN on an individual pillar and a total average force of ∼7.68 μN. We show that the middle of C. elegans exerts more force than its extremities. We find that C. elegans mutants with defective body wall muscles apply significantly lower force on individual pillars, while mutants defective in sensing externally applied mechanical forces still apply the same average force per pillar compared to wild type animals. Average forces applied per pillar are independent of the length, diameter, or cuticle stiffness of the animal. We also used the device to measure, for the first time, forces applied by Drosophila melanogaster larvae. Peristaltic waves occurred at 0.4 Hz applying an average force of ∼1.58 μN on a single pillar. Our colored microfluidic device along with its displacement tracking software allows us to measure forces applied by multiple model organisms that crawl or slither to travel through their environment.  相似文献   

18.
Sodium-based dual-ion batteries (Na-DIBs) show a promising potential for large-scale energy storage applications due to the merits of environmental friendliness and low cost. However, Na-DIBs are generally subject to poor rate capability and cycling stability for the lack of suitable anodes to accommodate large Na+ ions. Herein, we propose a molecular grafting strategy to in situ synthesize tin pyrophosphate nanodots implanted in N-doped carbon matrix (SnP2O7@N-C), which exhibits a high fraction of active SnP2O7 up to 95.6 wt% and a low content of N-doped carbon (4.4 wt%) as the conductive framework. As a result, this anode delivers a high specific capacity ∼400 mAh g−1 at 0.1 A g−1, excellent rate capability up to 5.0 A g−1 and excellent cycling stability with a capacity retention of 92% after 1200 cycles under a current density of 1.5 A g−1. Further, pairing this anode with an environmentally friendly KS6 graphite cathode yields a SnP2O7@N-C||KS6 Na-DIB, exhibiting an excellent rate capability up to 30 C, good fast-charge/slow-discharge performance and long-term cycling life with a capacity retention of ∼96% after 1000 cycles at 20 C. This study provides a feasible strategy to develop high-performance anodes with high-fraction active materials for Na-based energy storage applications.  相似文献   

19.
Activated carbon fabrics (ACF) mask prevents the absorption of lead and reduce its adverse effects of human health. Aim of this study to know the blood lead level and its effects on heme biosynthesis and hematological parameters after using 2 months activated carbon fabric mask of battery manufacturing workers (BMW). Blood lead level, heme biosynthesis and hematological parameters were measured by using standard method. Blood lead level (P < 0.001, − 13.5%) was significantly decreased, activated δ-aminolevulinic acid dehydratase (P < 0.001, 11.97%) and non-activated δ- aminolevulinic acid dehydratase (P < 0.001, 23.17%) enzyme activity were significantly increased, however, the ratio of activated to Non-activated δ- ALAD (P < 0.001, − 10.13%) was significantly decreased, urinary excretion of δ- aminolevulinic acid (P < 0.001, − 10.49%) and porphobilinogen (P < 0.001, − 7.38%) were significantly decreased after using 2 months ACF mask as compared to before using mask of BMW. Hematological parameters i.e Hb (P < 0.05, 13.42%), PCV (P < 0.05, 7.23%), MCV (P < 0.05, 1.9%) were significantly increased and total WBC count (P < 0.05, − 5.18%) was significantly decreased after using 2 months ACF mask as compared to before using mask of BMW. Two months using ACF mask reduces the blood lead level and improves the δ-ALDH activity and hematological parameters, decreases the urinary excretion of δ-ALA, PBG of battery manufacturing workers. Therefore, the regular using of ACF mask is beneficial to prevent the lead absorption and its adverse effects on human health.  相似文献   

20.
Cryopreservation of human red blood cells (RBCs) in the presence of 40% glycerol allows a shelf-life of 10 years, as opposed to only 6 weeks for refrigerated RBCs. Nonetheless, cryopreserved blood is rarely used in clinical therapy, in part because of the requirement for a time-consuming (∼1 h) post-thaw wash process to remove glycerol before the product can be used for transfusion. The current deglycerolization process involves a series of saline washes in an automated centrifuge, which gradually removes glycerol from the cells in order to prevent osmotic damage. We recently demonstrated that glycerol can be extracted in as little as 3 min without excessive osmotic damage if the composition of the extracellular solution is precisely controlled. Here, we explore the potential for carrying out rapid glycerol extraction using a membrane-based microfluidic device, with the ultimate goal of enabling inline washing of cryopreserved blood. To assist in experimental design and device optimization, we developed a mass transfer model that allows prediction of glycerol removal, as well as the resulting cell volume changes. Experimental measurements of solution composition and hemolysis at the device outlet are in reasonable agreement with model predictions, and our results demonstrate that it is possible to reduce the glycerol concentration by more than 50% in a single device without excessive hemolysis. Based on these promising results, we present a design for a multistage process that is predicted to safely remove glycerol from cryopreserved blood in less than 3 min.  相似文献   

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