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1.
Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the US and other parts of the world. There are conflicting reports on the serum levels of testosterone and 17β-estradiol (E2) in benign prostatic hyperplasia (BPH) and prostate cancer. This study was designed to evaluate the serum concentrations of these hormones in patients with these disorders. Serum levels of prostate specific antigen (PSA), total testosterone and estradiol were determined in 228 subjects comprising of 116 subjects with BPH, 62 subjects with prostate cancer (CaP) and 50 age-matched apparently healthy controls, using ELISA methods. PSA levels were significantly elevated (p < 0.05) in BPH subjects than controls, while there was no significant difference (p > 0.05) in testosterone and estradiol levels of these subjects. PSA and estradiol levels were significantly higher (p < 0.05) in CaP subjects than in controls, while there was no observed significant difference (p > 0.05) in testosterone levels. CaP subjects had significantly raised PSA, testosterone, and estradiol levels than BPH subjects. The mean molar ratio of testosterone: E2 was lowest among CaP patients (134:1) and highest among controls (166:1). Significant positive correlation between PSA and 17β-estradiol was observed in prostate disorders (BPH and CaP patients: r = 0.347; p = 0.000). Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = −0.221, p = 0.049) and control subjects (r = −0.490, p = 0.000). No significant correlation existed between testosterone and PSA in CaP patients (r = 0.051, p = 0.693). Correlations between age and estradiol in both BPH and CaP were not significant (p > 0.05). This study has shown that, there was a significant increase in serum estradiol in CaP subjects, while the testosterone levels in both BPH and CaP subjects were not different from those of controls.  相似文献   

2.
Acoustic trapping of minute bead amounts against fluid flow allows for easy automation of multiple assay steps, using a convenient aspirate/dispense format. Here, a method based on acoustic trapping that allows sample preparation for immuno-matrix-assisted laser desorption/ionization mass spectrometry using only half a million 2.8 μm antibody covered beads is presented. The acoustic trapping is done in 200 × 2000 μm2 glass capillaries and provides highly efficient binding and washing conditions, as shown by complete removal of detergents and sample processing times of 5-10 min. The versatility of the method is demonstrated using an antibody against Angiotensin I (Ang I), a peptide hormone involved in hypotension. Using this model system, the acoustic trapping was efficient in enriching Angiotensin at 400 pM spiked in plasma samples.  相似文献   

3.
Deterministic lateral displacement (DLD) is a microfluidic size-based particle separation or filter technology with applications in cell separation and enrichment. Currently, there are no cost-effective manufacturing methods for this promising microfluidic technology. In this fabrication paper, however, we develop a simple, yet robust protocol for thermoplastic DLD devices using regulatory-approved materials and biocompatible methods. The final standalone device allowed for volumetric flow rates of 660 μl min−1 while reducing the manufacturing time to <1 h. Optical profilometry and image analysis were employed to assess manufacturing accuracy and precision; the average replicated post height was 0.48% less than the average post height on the master mold and the average replicated array pitch was 1.1% less than the original design with replicated posts heights of 62.1 ± 5.1 μm (mean ± 6 standard deviations) and replicated array pitches of 35.6 ± 0.31 μm.  相似文献   

4.
For the first time, we report on the preliminary evaluation of gold coated optical fibers (GCOFs) as three-dimensional (3D) electrodes for a membraneless glucose/O2 enzymatic biofuel cell. Two off-the-shelf 125 μm diameter GCOFs were integrated into a 3D microfluidic chip fabricated via rapid prototyping. Using soluble enzymes and a 10 mM glucose solution flowing at an average velocity of 16 mm s−1 along 3 mm long GCOFs, the maximum power density reached 30.0 ± 0.1 μW cm−2 at a current density of 160.6 ± 0.3 μA cm−2. Bundles composed of multiple GCOFs could further enhance these first results while serving as substrates for enzyme immobilization.  相似文献   

5.
Separation and sorting of biological entities (viruses, bacteria, and cells) is a critical step in any microfluidic lab-on-a-chip device. Acoustofluidics platforms have demonstrated their ability to use physical characteristics of cells to perform label-free separation. Bandpass-type sorting methods of medium-sized entities from a mixture have been presented using acoustic techniques; however, they require multiple transducers, lack support for various target populations, can be sensitive to flow variations, or have not been verified for continuous flow sorting of biological cells. To our knowledge, this paper presents the first acoustic bandpass method that overcomes all these limitations and presents an inherently reconfigurable technique with a single transducer pair for stable continuous flow sorting of blood cells. The sorting method is first demonstrated for polystyrene particles of sizes 6, 10, and 14.5 μm in diameter with measured purity and efficiency coefficients above 75 ± 6% and 85 ± 9%, respectively. The sorting strategy was further validated in the separation of red blood cells from white blood cells and 1 μm polystyrene particles with 78 ± 8% efficiency and 74 ± 6% purity, respectively, at a flow rate of at least 1 μl/min, enabling to process finger prick blood samples within minutes.  相似文献   

6.
Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs.  相似文献   

7.
Recent years have witnessed a strong trend towards analysis of single-cells. To access and handle single-cells, many new tools are needed and have partly been developed. Here, we present an improved version of a single-cell printer which is able to deliver individual single cells and beads encapsulated in free-flying picoliter droplets at a single-bead efficiency of 96% and with a throughput of more than 10 beads per minute. By integration of acoustophoretic focusing, the cells could be focused in x and y direction. This way, the cells were lined-up in front of a 40 μm nozzle, where they were analyzed individually by an optical system prior to printing. In agreement with acoustic simulations, the focusing of 10 μm beads and Raji cells has been achieved with an efficiency of 99% (beads) and 86% (Raji cells) to a 40 μm wide center region in the 1 mm wide microfluidic channel. This enabled improved optical analysis and reduced bead losses. The loss of beads that ended up in the waste (because printing them as single beads arrangements could not be ensured) was reduced from 52% ± 6% to 28% ± 1%. The piezoelectric transducer employed for cell focusing could be positioned on an outer part of the device, which proves the acoustophoretic focusing to be versatile and adaptable.  相似文献   

8.
The main objective of this study is to evaluate the anti-hypertrophic potential of the aqueous extract of Enicostemma littorale (E. littorale) against isoproterenol induced cardiac hypertrophic rat models (male albino Wistar rats) through biochemical investigations. Aqueous extract of E. littorale known for various beneficial properties was administered (100 mg/kg, 12 days, oral) to isoproterenol (ISO) induced cardiac hypertrophic rats (low ISO—60 mg/kg, 12 days and high ISO—100 mg/kg, 12 days, subcutaneous) and were compared with group that was treated with the reference drug, Losartan (10 mg kg, administered for 12 days, oral). The anti-hypertrophic effect of E. littorale was evaluated by analysing the morphometric indices of the heart, ECG tracings, changes in blood biochemical parameters viz., serum glucose, serum total protein, serum albumin, lipid profile, cardiac specific enzymes (SGOT, SGPT and LDH) and histopathological examination of the heart tissue. The results fundamentally revealed that the plant extract efficiently ameliorated cardiac hypertrophy induced by ISO injected in experimental rats. The outcomes of biochemical investigations of this study highlighted the association between the hypertrophic β-adrenergic receptor signalling (β-AR) and the 5′ AMP-activated protein kinase (AMPK)—peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) axis in the metabolism of cardiac fibrosis and hypertrophy. This β-AR/AMPK-PGC1α signalling stem can serve as a key target in ameliorating cardiac hypertrophy through focus on its principal regulators. To add, we also propose that the glycoside, swertiamarin present in this plant with the reported anti-fibrotic potential in liver can be further isolated and evaluated for its anti-hypertrophic potential to treat cardiac hypertrophy.  相似文献   

9.
We report a refillable and valveless drug delivery device actuated by an external magnetic field for on-demand drug release to treat localized diseases. The device features a pear-shaped viscoelastic magnetic membrane inducing asymmetrical deflection and consecutive touchdown motion to the bottom of the dome-shaped drug reservoir in response to a magnetic field, thus achieving controlled discharge of the drug. Maximum drug release with 18 ± 1.5 μg per actuation was achieved under a 500 mT magnetic flux density, and various controlled drug doses were investigated with the combination of the number of accumulated actuations and the strength of the magnetic field.  相似文献   

10.
The majority of available cardiomyocyte markers are intercellular proteins, limiting our ability to enrich live cardiomyocytes from heterogeneous cell preparations in the absence of genetic labeling. Here, we describe enrichment of live cardiomyocytes from the hearts of adult mice in a label-free microfluidic approach. The separation device consisted of a vertical column (15 mm long, 700 μm diameter), placed between permanent magnets resulting in a field strength of 1.23 T. To concentrate the field at the column wall, the column was wrapped with 69 μm diameter nickel wire. Before passing the cells through the column, the cardiomyocytes in the cell suspension had been rendered paramagnetic by treatment of the adult mouse heart cell preparation with sodium nitrite (2.5 mM) for 20 min on ice. The cell suspension was loaded into the vertical column from the top and upon settling, the non-myocytes were removed by the upward flow from the column. The cardiomyocytes were then collected from the column by applying a higher flow rate (144 μl/min). We found that by applying a separation flow rate of 4.2 μl/min in the first step, we can enrich live adult cardiomyocytes to 93% ± 2% in a label-free manner. The cardiomyocytes maintained viability immediately after separation and upon 24 h in culture.  相似文献   

11.
Label-free isolation of single cells is essential for the growing field of single-cell analysis. Here, we present a device which prints single living cells encapsulated in free-flying picoliter droplets. It combines inkjet printing and impedance flow cytometry. Droplet volume can be controlled in the range of 500 pl–800 pl by piezo actuator displacement. Two sets of parallel facing electrodes in a 50 μm × 55 μm channel are applied to measure the presence and velocity of a single cell in real-time. Polystyrene beads with <5% variation in diameter generated signal variations of 12%–17% coefficients of variation. Single bead efficiency (i.e., printing events with single beads vs. total number of printing events) was 73% ± 11% at a throughput of approximately 9 events/min. Viability of printed HeLa cells and human primary fibroblasts was demonstrated by culturing cells for at least eight days.  相似文献   

12.
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   

13.
Understanding the correlation between exposed surfaces and performances of controlled nanocatalysts can aid effective strategies to enhance electrocatalysis, but this is as yet unexplored for the nitrogen reduction reaction (NRR). Here, we first report controlled synthesis of well-defined Pt3Fe nanocrystals with tunable morphologies (nanocube, nanorod and nanowire) as ideal model electrocatalysts for investigating the NRR on different exposed facets. The detailed electrocatalytic studies reveal that the Pt3Fe nanocrystals exhibit shape-dependent NRR electrocatalysis. The optimized Pt3Fe nanowires bounded with high-index facets exhibit excellent selectivity (no N2H4 is detected), high activity with NH3 yield of 18.3 μg h−1 mg−1cat (0.52 μg h−1 cm−2ECSA; ECSA: electrochemical active surface area) and Faraday efficiency of 7.3% at −0.05 V versus reversible hydrogen electrode, outperforming the {200} facet-enclosed Pt3Fe nanocubes and {111} facet-enclosed Pt3Fe nanorods. They also show good stability with negligible activity change after five cycles. Density functional theory calculations reveal that, with high-indexed facet engineering, the Fe-3d band is an efficient d-d coupling correlation center for boosting the Pt 5d-electronic exchange and transfer activities towards the NRR.  相似文献   

14.
We describe a scalable artificial bilayer lipid membrane platform for rapid electrophysiological screening of ion channels and transporters. A passive pumping method is used to flow microliter volumes of ligand solution across a suspended bilayer within a microfluidic chip. Bilayers are stable at flow rates up to ∼0.5 μl/min. Phospholipid bilayers are formed across a photolithographically defined aperture made in a dry film resist within the microfluidic chip. Bilayers are stable for many days and the low shunt capacitance of the thin film support gives low-noise high-quality single ion channel recording. Dose-dependent transient blocking of α-hemolysin with β-cyclodextrin (β-CD) and polyethylene glycol is demonstrated and dose-dependent blocking studies of the KcsA potassium channel with tetraethylammonium show the potential for determining IC50 values. The assays are fast (30 min for a complete IC50 curve) and simple and require very small amounts of compounds (100 μg in 15 μl). The technology can be scaled so that multiple bilayers can be addressed, providing a screening platform for ion channels, transporters, and nanopores.  相似文献   

15.
Severe hemolytic anemia in β-thalassemia major and β-thalassemias/HbE (β-TM) patients requires giving blood transfusions. Chronic blood transfusions lead to iron overload consequence with organs damage and risk of alloantibody-formation. This study evaluates the prevalence of red cell alloimmunization and estimates the risk of alloantibody-formation in chronic transfusion-dependent β-TM patients. This cross sectional study was conducted on 143 β-TM patients receiving regular transfusions. We tried to determine the frequency, types and factors influencing red cell alloimmunization in these transfusion-dependent β-TM patients. Median age of 25 (17.5 %) alloantibody-formation β-TM patients was 19.0 years (inter quartile 15.5–24.0 years). The alloantibodies were Anti-Rh (E) (13.1 %), Anti-Rh (D) (0.7 %). Thirty-four patients (23.8 %) of the sample had splenectomies of which 10 (29.4 %) had alloantibody-formation. The interval from first transfusion to antibody development varied from 1.5 to 14 years. Alloantibody-formation correlated with splenectomy and splenectomy correlated with number of transfusion (p < 0.005). In multiple logistic regression used to estimate the risk of alloantibodies formation with splenectomy; OR and 95 % CI were 2.88 (1.07–7.80), p = 0.037 after adjusting for other co-variates. The rate of red cell alloimmunization was 17.5 % and splenectomy associated with increased alloantibody-formation in these transfusion-dependent β-TM patients.  相似文献   

16.
As a non-invasive therapeutic method without penetration-depth limitation, magnetic hyperthermia therapy (MHT) under alternating magnetic field (AMF) is a clinically promising thermal therapy. However, the poor heating conversion efficiency and lack of stimulus–response obstruct the clinical application of magnetofluid-mediated MHT. Here, we develop a ferrimagnetic polyethylene glycol-poly(2-hexoxy-2-oxo-1,3,2-dioxaphospholane) (mPEG-b-PHEP) copolymer micelle loaded with hydrophobic iron oxide nanocubes and emodin (denoted as EMM). Besides an enhanced magnetic resonance (MR) contrast ability (r2 = 271 mM−1 s−1) due to the high magnetization, the specific absorption rate (2518 W/g at 35 kA/m) and intrinsic loss power (6.5 nHm2/kg) of EMM are dozens of times higher than the clinically available iron oxide nanoagents (Feridex and Resovist), indicating the high heating conversion efficiency. Furthermore, this composite micelle with a flowable core exhibits a rapid response to magnetic hyperthermia, leading to an AMF-activated supersensitive drug release. With the high magnetic response, thermal sensitivity and magnetic targeting, this supersensitive ferrimagnetic nanocomposite realizes an above 70% tumor cell killing effect at an extremely low dosage (10 μg Fe/mL), and the tumors on mice are completely eliminated after the combined MHT–chemotherapy.  相似文献   

17.
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   

18.
This article describes a fabrication process for the generation of a leak proof paper based microfluidic device and a new design strategy for convenient incorporation of externally prepared test zones. Briefly, a negative photolithographic method was used to prepare the device with a partial photoresist layer on the rear of the device to block the leakage of sample. Microscopy and Field Emission Scanning Electron Microscopy data validated the formation of the photoresist layer. The partial layer of photoresist on the device channel limits sample volume to 7 ± 0.2 μl as compared to devices without the partial photoresist layer which requires a larger sample volume of 10 ± 0.1 μl. The design prototype with a customized external test zone exploits the channel protrusions on the UV exposed photoresist treated paper to bridge the externally applied test zone to the sample and absorbent zones. The partially laminated device with an external test zone has a comparatively low wicking speed of 1.8 ± 0.9 mm/min compared to the completely laminated device with an inbuilt test zone (3.3 ± 1.2 mm/min) which extends the reaction time between the analyte and reagents. The efficacy of the prepared device was studied with colorimetric assays for the non-specific detection of protein by tetrabromophenol blue, acid/base with phenolphthalein indicator, and specific detection of proteins using the HRP-DAB chemistry. The prepared device has the potential for leak proof detection of analyte, requires low sample volume, involves reduced cost of production (∼$0.03, excluding reagent and lamination cost), and enables the integration of customized test zones.  相似文献   

19.
This paper presents a vertically positioned microfluidic system made of poly(dimethylsiloxane) (PDMS) and glass, which can be applied as a microbubble column (μBC) for biotechnological screening in suspension. In this μBC, microbubbles are produced in a cultivation chamber through an integrated nozzle structure. Thus, homogeneous suspension of biomass is achieved in the cultivation chamber without requiring additional mixing elements. Moreover, blockage due to produced carbon dioxide by the microorganisms—a problem predominant in common, horizontally positioned microbioreactors (MBRs)—is avoided, as the gas bubbles are released by buoyancy at the upper part of the microsystem. The patterned PDMS layer is based on an optimized two-lithographic process. Since the naturally hydrophobic PDMS causes problems for the sufficient production of microbubbles, a method based on polyelectrolyte multilayers is applied in order to allow continuous hydrophilization of the already bonded PDMS-glass-system. The μBC comprises various microelements, including stabilization of temperature, control of continuous bubble formation, and two optical configurations for measurement of optical density with two different sensitivities. In addition, the simple and robust application and handling of the μBC is achieved via a custom-made modular plug-in adapter. To validate the scalability from laboratory scale to microscale, and thus to demonstrate the successful application of the μBC as a screening instrument, a batch cultivation of Saccharomyces cerevisiae is performed in the μBC and compared to shake flask cultivation. Monitoring of the biomass growth in the μBC with the integrated online analytics resulted in a specific growth rate of 0.32 h−1, which is almost identical to the one achieved in the shake flask cultivation (0.31 h−1). Therefore, the validity of the μBC as an alternative screening tool compared to other conventional laboratory scale systems in bioprocess development is proven. In addition, vertically positioned microbioreactors show high potential in comparison to conventional screening tools, since they allow for high density of integrated online analytics and therefore minimize time and cost for screening and guarantee improved control and analysis of cultivation parameters.  相似文献   

20.
We report the successful fabrication and testing of 3D printed microfluidic devices with integrated membrane-based valves. Fabrication is performed with a low-cost commercially available stereolithographic 3D printer. Horizontal microfluidic channels with designed rectangular cross sectional dimensions as small as 350 μm wide and 250 μm tall are printed with 100% yield, as are cylindrical vertical microfluidic channels with 350 μm designed (210 μm actual) diameters. Based on our previous work [Rogers et al., Anal. Chem. 83, 6418 (2011)], we use a custom resin formulation tailored for low non-specific protein adsorption. Valves are fabricated with a membrane consisting of a single build layer. The fluid pressure required to open a closed valve is the same as the control pressure holding the valve closed. 3D printed valves are successfully demonstrated for up to 800 actuations.  相似文献   

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