Capillary Device Research Articles

The impact of automatic devices for capillary blood collection on efficiency and pain response in newborns: A randomized controlled trial

BackgroundThe heel stick is the method of choice in most neonatal units for capillary blood sampling, and it represents the most common event among all painful procedures performed on newborns. The type and design of heel stick device and the clinical procedure to collect a blood sample may have an impact on newborn pain response as well. ObjectiveTo compare the pain response and efficiency of different automated devices for capillary blood collection in newborns. DesignRandomized clinical trial. SettingPostnatal ward of a tertiary-care university hospital in Italy. ParticipantsNewborn infants at gestational age ≥34 weeks undergoing the metabolic screening test after the 49th hour of life. MethodsA total of 762 neonates were recruited and randomized into 6 groups (127 babies in each group) assigned to 6 different capillary blood collection devices (Ames Minilet™ Lancet; Cardinal Health Gentleheel®; Natus Medical NeatNick™; BD Quikheel™ Lancet; Vitrex Steriheel® Baby Lancet; Accriva Diagnostics Tenderfoot®). Main outcome measuresThe following data were collected and assessed for each of the 6 groups evaluated: a) number of heel sticks, b) pain score according to the Neonatal Infant Pain Scale (NIPS) and c) need to squeeze the heel. ResultsThe Ames Minilet™ Lancet device was found to perform by far the worst compared to the five device underexamination: it required the highest number of sticks (mean=3.91; 95% CI: 3.46–4.36), evoked the most intense pain (mean=3.98; 95% CI: 3.77–4.20), and most frequently necessitated squeezing the heel (92.9%; 95% CI: 86.9–96.3). The five devices under examination appeared to be similar in terms of the number of sticks required, but differed slightly in NIPS score and in need to squeeze the heel. ConclusionThe Accriva Diagnostics Tenderfoot® device demonstrated the greatest efficiency for blood sampling and evoked the least pain. With this device, the metabolic screening test could be performed with a single skin incision in the large majority of infants (98.4%), heel squeezing was limited to only 6.3% of infants, and the NIPS score turns out to be lower than other devices in our study (1.22; 95% CI 1.05–1.39).

Continuously Electrotriggered Core Coalescence of Double-Emulsion Drops for Microreactions.

Microfluidically generated double emulsions are promising templates for microreactions, which protect the reaction from external disturbance and enable in vitro analyses with large-scale samples. Controlled combination of their inner droplets in a continuous manner is an essential requirement toward truly applications. Here, we first generate dual-cored double-emulsion drops with different inner encapsulants using a capillary microfluidic device; next, we transfer the emulsion drops into another electrode-integrated polydimethylsiloxane microfluidic device and utilize external AC electric field to continuously trigger the coalescence of inner cores inside these emulsion drops in continuous flow. Hundreds of thousands of monodisperse microreactions with nanoliter-scale reagents can be conducted using this approach. The performance of core coalescence is investigated as a function of flow rate, applied electrical signal, and core conductivity. The coalescence efficiency can reach up to 95%. We demonstrate the utility of this technology for accommodating microreactions by analyzing an enzyme catalyzed reaction and by fabricating cell-laden hydrogel particles. The presented method can be readily used for the controlled triggering of microreactions with high flexibility for a wide range of applications, especially for continuous chemical or cell assays.

Sensitive Detection of MMP9 Enzymatic Activities in Single Cell-Encapsulated Microdroplets as an Assay of Cancer Cell Invasiveness.

Matrix metalloproteinases (MMPs) are typically up-regulated in cancer cells, and play a critical role in assisting metastasis by the breakdown of the extracellular matrix. Here we report an effective strategy for cell invasiveness assay by integrating MMP9 functional activity analysis with single cell-encapsulated microdroplets. A flow focusing capillary microfluidic device has been assembled using "off-the-shelf" fluidic components for high-throughput generation of microdroplets. Tumor cells, MMP9 specific peptides, and other cofactors can be loaded into the device and encapsulated into individual droplets as dynamic microreactors for proteolytic cleavage of the substrate. This design allows for rapid and robust detection of MMP9 enzymatic activities by fluorescent signals in a few minutes. It represents the first demonstration of quantifying MMP9 enzymatic activities at the single cell level with a high throughput performance. This new technique promises functional evaluation of cancer cell invasiveness for important diagnostic or prognostic applications.

Capillary flow-driven microfluidic device with wettability gradient and sedimentation effects for blood plasma separation

We report a capillary flow-driven microfluidic device for blood-plasma separation that comprises a cylindrical well between a pair of bottom and top channels. Exposure of the well to oxygen-plasma creates wettability gradient on its inner surface with its ends hydrophilic and middle portion hydrophobic. Due to capillary action, sample blood self-infuses into bottom channel and rises up the well. Separation of plasma occurs at the hydrophobic patch due to formation of a ‘self-built-in filter’ and sedimentation. Capillary velocity is predicted using a model and validated using experimental data. Sedimentation of RBCs is explained using modified Steinour’s model and correlation between settling velocity and liquid concentration is found. Variation of contact angle on inner surface of the well is characterized and effects of well diameter and height and dilution ratio on plasma separation rate are investigated. With a well of 1.0 mm diameter and 4.0 mm height, 2.0 μl of plasma was obtained (from <10 μl whole blood) in 15 min with a purification efficiency of 99.9%. Detection of glucose was demonstrated with the plasma obtained. Wetting property of channels was maintained by storing in DI water under vacuum and performance of the device was found to be unaffected over three weeks.

Integrating Internal Standards into Disposable Capillary Electrophoresis Devices To Improve Quantification.

To improve point-of-care quantification using microchip capillary electrophoresis (MCE), the chip-to-chip variabilities inherent in disposable, single-use devices must be addressed. This work proposes to integrate an internal standard (ISTD) into the microchip by adding it to the background electrolyte (BGE) instead of the sample—thus eliminating the need for additional sample manipulation, microchip redesigns, and/or system expansions required for traditional ISTD usage. Cs and Li ions were added as integrated ISTDs to the BGE, and their effects on the reproducibility of Na quantification were explored. Results were then compared to the conclusions of our previous publication which used Cs and Li as traditional ISTDs. The in-house fabricated microchips, electrophoretic protocols, and solution matrixes were kept constant, allowing the proposed method to be reliably compared to the traditional method. Using the integrated ISTDs, both Cs and Li improved the Na peak area reproducibility approximately 2-fold, to final RSD values of 2.2–4.7% (n = 900). In contrast (to previous work), Cs as a traditional ISTD resulted in final RSDs of 2.5–8.8%, while the traditional Li ISTD performed poorly with RSDs of 6.3–14.2%. These findings suggest integrated ISTDs are a viable method to improve the precision of disposable MCE devices—giving matched or superior results to the traditional method in this study while neither increasing system cost nor complexity.

Nanovaccines: Multistaged Nanovaccines Based on Porous Silicon@Acetalated Dextran@Cancer Cell Membrane for Cancer Immunotherapy (Adv. Mater. 7/2017)

In article 1603239, Flavia Fontana, Helder A. Santos, and co-workers develop an innovative cancer nanovaccine by merging the adjuvant properties of the nanoparticles produced by nanoprecipitation in a microfluidic glass capillary device with high reproducibility, together with a biomimetic source of antigens derived from cancer-cell membranes. The nanovectors induce maturation of antigen-presenting cells and secretion of pro-inflammatory cytokines in vitro.

Analysis of Methanol in the Presence of Ethanol, Using a Hybrid Capillary Electrophoresis Device with Electrochemical Derivatization and Conductivity Detection.

Concurrently with ethanol, many other compounds can be formed during the fermentation of grains and fruits. Among those, methanol is particularly important (because of its toxicity) and is typically formed at concentrations much lower than ethanol, presenting a particular challenge that demands the implementation of separation techniques. Aiming to provide an alternative to traditional chromatographic approaches, a hybrid electrophoresis device with electrochemical preprocessing and contactless conductivity detection (hybrid EC-CE-C4D) is herein described. The device was applied to perform the electro-oxidation of primary alcohols, followed by the separation and detection of the respective carboxylates. According to the presented results, the optimum conditions were obtained when the sample was diluted with 2 mmol L-1 HNO3 and then electro-oxidized by applying a potential of 1.4 V for 60 s. The oxidation products were then electrokinetically injected by applying a potential of 3 kV for 4 s and separated using a potential of 3 kV and a background running electrolyte (BGE) consisting of 10 mmol L-1 N-cyclohexyl-2-aminoethanesulfonic acid (CHES) and 5 mmol L-1 sodium hydroxide (NaOH). n-Propanol was used as an internal standard and the three carboxylate peaks were resolved with baseline separation within <3 min, defining linear calibration curves in the range of 0.10-5.0 mmol L-1. Limits of detection (LODs) of 20, 40, and 50 μmol L-1 were obtained for ethanol, n-propanol, and methanol, respectively. To demonstrate the applicability of the proposed strategy, a laboratory-made sample (moonshine) was used. Aliquots collected along the beginning of the fractional distillation presented a decreasing methanol ratio (from 4% to <0.5%) and a growing ethanol ratio (from 80% to 100%) in the collected volume.

Open channel deterministic lateral displacement for particle and cell sorting.

We present the use of capillary driven flow over patterned surfaces to achieve cheap and simple, but powerful separation of biologically relevant particle systems. The wide use of microfluidics is often hampered by the propensity for devices to clog due to the small channel sizes and the inability to access the interior of devices for cleaning. Often the devices can only be used for a limited duration and most frequently only once. In addition the cost and power requirements of flow control equipment limits the wider spread of the devices. We address these issues by presenting a simple particle- and cell-sorting scheme based on controlled fluid flow on a patterned surface. The open architecture makes it highly robust and easy to use. If clogging occurs it is straightforward to rinse the device and reuse it. Instead of external mechanical pumps, paper is used as a capillary pump. The different fractions are deposited in the paper and can subsequently be handled independently by simply cutting the paper for downstream processing and analyses. The sorting, based on deterministic lateral displacement, performs equivalently well in comparison with standard covered devices. We demonstrate successful separation of cancer cells and parasites from blood with good viability and with relevance for diagnostics and sample preparation. Sorting a mixture of soil and blood, we show the potential for forensic applications.

A low-cost, plug-and-play inertial microfluidic helical capillary device for high-throughput flow cytometry.

Glass capillary tubes have been widely used in microfluidics for generating microdroplets and microfibers. Here, we report on the application of glass capillary to inertial focusing of microparticles and cells for high-throughput flow cytometry. Our device uses a commercially available capillary tube with a square cross-section. Wrapping the tube into a helical shape induces the Dean vortices that aid focusing of cells or microbeads into a single position. We investigated the inertial focusing of microbeads in the device at various Re and concentrations and demonstrated 3D focusing with ∼100% efficiency for a wide range of microparticle diameters. We integrated the device with a laser counting system and demonstrated continuous counting of 10 μm microbeads with a high throughput of 13 000 beads/s as well as counting of fluorescently labeled white blood cells in the diluted whole blood. The helical capillary device offers a number of key advantages, including rapid and ultra-low-cost plug-and-play fabrication, optical transparency, and full compatibility with bright field or fluorescent imaging, easy re-configurability of the device radius for tuning focusing behavior, and ability to rotate for easy side-wall observation. With precise and consistent 3D focusing of microbeads and cells with a wide range of sizes at high throughput and without the use of sheath flows, we envision that this simple capillary-based inertial microfluidic device will create new opportunities for this technique to be widely adopted in the laboratory research.

A wavelike buffer for introducing samples into autonomous capillary microfluidic devices

The microfluidic technique has gained attention due to its advantages in providing a rapid diagnostic result for on-site diagnosis and treatment. To obtain a quantitative and reproducible diagnostic result the fluid flow in the microfluidic device must be steady. However, a non-specific flow will always form due to the disturbances introduced during the sample injecting process. Here, a wavelike sample introduction buffer is presented. The buffer can change the longitudinal flow of the injected sample to a transverse flow, which will consume the kinetic energy and eliminate disturbances. By using the buffer, fluid flow within a microfluidic device can become steady. The effects of the buffer parameters on buffering performance have been studied. Results show that the buffering performance increases as the waved peak height and peak number decrease. This buffer has a simple structure. It requires no external power supplies or complicated fabrication process. It will be helpful in improving the diagnostic accuracy of microfluidic devices.

A reproducible approach to the assembly of microcapillaries for double emulsion production

Double emulsions attract considerable interest for their utility in applications as diverse as drug delivery, contrast agents, and compartmentalizing analytes for fluorescence-activated cell sorting. Microfluidic platforms offer a particularly elegant approach to generating these structures, but the construction of devices to provide reproducible and stable production of double emulsions remains challenging. PDMS-based systems require specialized surface treatments that are difficult to implement and lack long-term stability, and current glass microcapillary systems, while offering some advantages, lack flexible and reproducible methods for capillary alignment. This article describes a microcapillary-based approach that addresses these key challenges. Our approach utilizes translational stage elements and alignment end caps that are fixed in place once configured, rather than tightly fitting capillaries. This new approach enables alignment to within ±10 µm and allows greater flexibility in choosing the dimensions of the capillary, which contributes to the size and stability of formation of the double emulsion. Importantly, it also allows the user to compensate for the deviations from ideal shape that occur in pulled glass capillaries, which has been a source of failure with previous methods. A detailed description of the critical design and operational parameters that affect double emulsion generation in these capillary microfluidic devices is provided.

Study on a New Ignition Method of the Spark Gap Based on Plasma Ejection in Air

AbstractA new ignition method of the spark gap based on plasma ejection is proposed in this paper, as the conventional trigatron spark gap performs poorly under the low working coefficient (the ratio of the charging voltage to the self‐breakdown voltage) in air. The plasma is generated by the capillary discharge, which has high pressure, high temperature and high velocity. The capillary discharge device is placed inside the low voltage electrode. As long as the triggering signal is sent to the device, a column of the plasma flow is ejected in axial direction and develops rapidly towards the high voltage electrode. Subsequently, the gap is broken down and a high resistive channel is formed, where the thermal ionization takes place and the arc across the whole gap is generated and develops into a well conductive channel. The process of the thermal ionization of the high resistive channel varies with the change of the spark gap distance. The breakdown delay and the delay jitter of the spark gap increase with the spark gap distance, as both parameters are mainly determined by the developing process of the plasma ejection. The characteristics of the plasma flow determine the possibility of the breakdown of the spark gap under the low working coefficient. The ignition method based on capillary plasma ejection has been proved by the preliminary experiments, which indicate that under the gap length of 8 cm and the working coefficient of less than 3%, the effective ignition is still achievable.

Multiplex determination of antigen specific antibodies with cell binding capability in a self-driven microfluidic system

Antibodies, induced during infections or in autoimmune diseases, exert their protective or destructive effects as part of an orchestrated system that contains several other immune system related proteins and cells. Accordingly immunological assessment of the humoral immune response should include not only the determination of antigen specific antibody level but also the capability of binding to effector cells. We designed and fabricated a polymer based modular autonomous capillary device with an integrated protein microarray that fulfills this need and enables simple, robust detection of antigen specific antibodies through their effector cell binding capability. Serum samples derived from rheumatoid arthritis patients, U937 monocytoid cells and cell stain were sequentially introduced into the self-driven device with disease specific printed citrullinated peptide antigens. The number of bound cells was determined by brightfield microscopic imaging. We found strong positive correlation between antibody level determined by conventional protein microarray technology and binding frequency of U937 cells. Detection by U937 cells was more sensitive than with secondary antibodies for one peptide antigen and less than 13 CV% was experienced in the reproducibility of the measurement.

Bicolored Janus Microparticles Created by Phase Separation in Emulsion Drops

In this work, a simple but versatile method to create bicolored Janus microparticles using phase separation of two immiscible polymers confined in emulsion drops is reported. With a capillary microfluidic device, monodisperse oil drops containing two immiscible polymers and dye molecules are generated in the continuous water phase. As the organic solvent is depleted by evaporation, the drops evolve to Janus microparticles with two compartments. One of the compartments is selectively stained by spontaneous migration of the dye molecules, thereby providing optical anisotropy. In addition, the Janus microparticles can be further rendered to be magneto‐responsive by embedding aligned magnetic nanoparticles in the polymer matrix. Moreover, the configuration of Janus microparticles is exclusively selected from the core‐incomplete shell, dumbbell, and acorn, according to the surfactant in the continuous phase. This phase separation approach will provide a new opportunity for designing Janus microparticles with advanced functionality. image

Capillary lactate concentration on admission of normotensive trauma patients: a prospective study.

BackgroundElevated serum blood lactate is an indicator of on-going bleeding in severe trauma patients. Point-of-care (POC) capillary lactate measurement devices may be useful to rapidly assess lactate concentration at the bedside. The aim of this study was to test the diagnostic performance of capillary lactate to predict significant transfusion in normotensive trauma patients.MethodsWe conducted a prospective observational study in one level-I trauma centre. From August 2011 to February 2013, 120 consecutive adult patients with systolic blood pressure (SBP) higher than 90 mmHg were included. Capillary lactate was measured on admission in the trauma bay. The primary outcome was defined as a significant transfusion within the first 48 h. Diagnostic performance was determined using receiver operating characteristic (ROC) curve analysis. We also tested the agreement between capillary lactate and blood lactate concentrations using Bland and Altman analysis.ResultsOf the 120 normotensive trauma patients, 30 (25 %) required at least one unit of packed red blood cells (RBC) and 12 (10 %) patients received at least four RBC within the first 48 h. All patients with significant RBC transfusion had capillary lactate higher than 3.5 mmol/l. The area under the ROC curve of capillary lactate on admission to predict transfusion of at least 4 RBC units was 0.68 [95 % CI 0.58 – 0.78]. The average bias between capillary and blood lactate measurements was 2.4 mmol/l with a standard deviation of 3.0 mmol/l (n = 60 patients).ConclusionsAlthough a significant association was found between POC lactate concentration and transfusion requirements, the diagnostic performance of capillary lactate measurements was poor. Due to large disagreement between capillary lactate and blood lactate, capillary lactate cannot be considered in the clinical setting.Trial registrationClinicalTrials.gov, No. NCT01793428.Electronic supplementary materialThe online version of this article (doi:10.1186/s13049-016-0272-x) contains supplementary material, which is available to authorized users.

Microfluidic-based generation of functional microfibers for biomimetic complex tissue construction

Microfluidic-based fiber system displays great potential in reconstructing naturally complex tissues. In these systems, fabrication of the basic fiber is a significant factor in ensuring a functional construction. The fiber should possess the strong mechanical rigidity for assembly, predefined microenvironment for cell spatial distribution and high biocompatibility for cell functional expression. Herein we presented a composite material by the combination of methacrylated gelatin (GelMA) and alginate for fiber engineering with capillary microfluidic device. Being regulated by GelMA incorporation, the composite hydrogels exhibited higher mechanical moduli, better stretching performance, and lower swelling compared to pure alginate one. On the basis of the composite material and capillary microfluidic device, we constructed the double-layer hollow microfibers to simulate complex tissues. The microfibers could be precisely controlled in size and multi-layered structure by varying flow rates and outlet diameter, and it showed satisfied application in woven-structure assembly. As an example to mimic a functional tissue, a biomimetic osteon-like structure was fabricated by encapsulating human umbilical vascular endothelial cells (HUVECs) in middle layer to imitate vascular vessel and human osteoblast-like cells (MG63) in the outer layer to act role of bone. During the incubation period, both MG63 and HUVECs exhibited not only a robust growth, but also up-regulated gene expression. These results demonstrated this microfluidic-based composite microfibers system is a promising alternative in complex tissue regeneration. Statement of SignificanceCell-laden microfibers based on microfluidic device is attracting interest for reconstructing naturally complex tissues. One shortage is the lack of suitable materials which satisfy microfluidic fabrication and cell biofunctional survival. This study reports the first combination of alginate-GelMA composite and capillary-based microfluidic technology. The composite materials possess high mechanical properties for fabrication and assembly, and tunable environment for cell spatial encapsulation. Significantly, the engineered double-layer hollow microfiber with osteon-like structure showed enhanced cellular bioactivity and realized initially functional establishment. This microfluidic-based composite microfiber not only explores a competitive candidate in complex tissues reconstruction, but also expands the biological application of microfluidic technology. This developing interdisciplinary area should be widely interested to the readers of biofabrication, biomaterials and tissue engineering.

Fast production of microfluidic devices by CO2 laser engraving of wax-coated glass slides.

Glass is one of the most convenient materials for the development of microfluidic devices. However, most fabrication protocols require long processing times and expensive facilities. As a convenient alternative, polymeric materials have been extensively used due their lower cost and versatility. Although CO2 laser ablation has been used for fast prototyping on polymeric materials, it cannot be applied to glass devices because the local heating causes thermal stress and results in extensive cracking. A few papers have shown the ablation of channels or thin holes (used as reservoirs) on glass but the process is still far away from yielding functional glass microfluidic devices. To address these shortcomings, this communication describes a simple method to engrave glass-based capillary electrophoresis devices using standard (1mm-thick) microscope glass slides. The process uses a sacrificial layer of wax as heat sink and enables the development of both channels (with semicircular shape) and pass-through reservoirs. Although microscope images showed some small cracks around the channels (that became irrelevant after sealing the engraved glass layer to PDMS) the proposed strategy is a leap forward in the application of the technology to glass. In order to demonstrate the capabilities of the approach, the separation of dopamine, catechol and uric acid was accomplished in less than 100s.

Advance in Microfluidic Devices for Fractionation of DNA Fragments

Abstract The next generation sequencing works faster and the price is coming down. However, the workflows have numerous manual processes, which will cause some bottleneck and contribute to inefficiency in gene sequencing. One of the most time-consuming steps is electrophoretic gel-based fractionation of a large number of fragments of interest during the library generation process. In recent years, several instruments were first introduced into the market, and then were tested by many famous DNA sequencing centers and platforms. This paper introduces the development of DNA fractionation techniques including capillary electrophoresis and microfluidic devices. Moreover, our argument raises the bottleneck in fractionating DNA fragments on the chips. Finally, we provide insights into the challenges of DNA fractionation and provide future perspectives.

Separation and determination of flavonoids in three traditional chinese medicines by capillary electrophoresis with amperometric detection.

Flavonoids are important active ingredients in many traditional Chinese medicines. In this paper, capillary electrophoresis with amperometric detection was employed to separate and detect eight flavonoids, rutin, quercetrin, quercetin, kaempferol, kaempferide, catechin, apigenin, and luteolin, in a home-made capillary electrophoresis device. Under the separation voltage of 2000 V, the eight flavonoids could be completely separated within 33 min in 18 mM borax running buffer at pH 10.2. Good linear relationships were obtained for all analytes and the detection limits for flavonoids ranged from 0.46 to 0.85 μM. Then, the method was applied to separate and determine the flavonoids in three traditional Chinese medicines, hippophae rhamnoides, hypericum perforatum, and cacumen platycladi. Finally, rutin, kaempferol, quercetin, and quercetrin were discovered in these medicines and the concentrations ranged from 0.28 to 9.94 mg/g. The recoveries of flavonoids ranged from 84.7 to 113%, which showed the high reliability of this method.

Microfluidic Production of Uniform Microcarriers with Multicompartments through Phase Separation in Emulsion Drops

Microfluidics has provided biodegradable microcarriers for sustained release of drugs, while allowing insignificant initial bursting. Here, we further engineer the microcarriers to have multiple compartments to release distinct drugs in a more controlled fashion. With a capillary microfluidic device, monodisperse emulsion drops containing two immiscible biocompatible polymers, one is biodegradable and the other is pH-responsive, are prepared, which undergo phase separation as the solvent in the drops is depleted. The emulsion drops finally form uniform microcarriers with distinct compartments. During the phase separation and consolidation, two model drugs with different hydrophobicity involved in the drops are spontaneously concentrated in their own compartments with higher affinity. The configuration of the microcarriers is exclusively selected from five different structures depending on the pair of polymers, pH of continuous phase, and organic solvent of emulsion drops; two of five have minimum interfac...