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Phosphate is important for plant and animal growth. Therefore, it is commonly added as a fertilizer in agricultural fields. Phosphorus is typically measured using colorimetric or electrochemical sensors. Colorimetric sensors suffer from a limited measuring range and toxic waste generation while electrochemical sensors suffer from long-term drifts due to reference electrodes. Here, we propose a solid-state, reagent-free and reference electrode-free chemiresistive sensor for measuring phosphate using single-walled carbon nanotubes functionalized with crystal violet. The functionalized sensor exhibited a measuring range from 0.1 mM to 10 mM at pH 8. No significant interference was observed for common interfering anions like nitrates, sulphates, and chlorides. This study showed a proof-of-concept chemiresistive sensor, which can potentially be used to measure phosphate levels in hydroponics and aquaponics systems. The dynamic measuring range further needs to be extended for surface water samples. [ABSTRACT FROM AUTHOR]

Protein C is a vitamin K dependant protein in plasma that plays an essential role in regulating the coagulation cascade and inflammatory response. As a result of its importance in these roles, it has been suggested as a biomarker for prognosis of patients affected by sepsis. Sepsis is a dysregulated host response to an infection that is the leading cause of mortality in U.S. hospitals and results in the highest cost of hospitalization. It was found that protein C concentration in non-surviving sepsis patients is significantly lower (1.8 μg mL−1) than in survivors and healthy patients who have a protein C concentration of 3.9–5.9 μg mL−1. Current methods for diagnosing sepsis rely on expensive immunoassays or functional assays that require multiple steps for isolation and activation of protein C. We demonstrate in this paper a low cost, single step assay for detection of protein C in blood plasma. This was done by combining isoelectric gates with barium-immobilized metal affinity trapping. The electric field was optimized for use with immobilized metal affinity using COMSOL simulation. The integrated device was tested with samples containing buffered protein C, protein C in the presence of high concentration bovine serum albumin and alpha 1-proteinase inhibitor, and in blood plasma with spiked protein C. The stability of the measured values was tested by monitoring the intensity of a mixture of protein C with BSA and A1PI every minute to determine that measurement after 40 minutes was optimal. The results showed that the device could be used to distinguish a reduction in protein C from 4.46 μg mL−1 to 1.96 μg mL−1 with greater than 98% confidence in plasma making it suitable for sepsis prognosis. [ABSTRACT FROM AUTHOR]

Many neonates who are born premature suffer from respiratory distress syndrome (RDS) for which mechanical ventilation and an extracorporeal membrane oxygenation (ECMO) device are used in treatment. However, the use of these invasive techniques results in higher risk of complications like bronchopulmonary dysplasia or requires surgery to gain vascular access. An alternative biomimetic approach is to use the umbilical cord as a vascular access and to connect a passive device to the baby that functions like a placenta. This concept, known as the artificial placenta, provides enough oxygenation and causes minimal distress or complications. Herein, we have developed a new artificial placenta-type microfluidic blood oxygenator (APMBO) with high gas exchange, low priming volume and low hydraulic resistance such that it can be operated only by pressure differential provided by the baby's heart. Mimicking the placenta, we have made our new device ultra-thin and flexible so that it can be folded into a desired shape without losing its capability for gas exchange and achieve a compact form factor. The ability to fold allowed optimization of connectors and reduced the overall priming volume to the sub-milliliter range while achieving a high oxygen uptake which would be sufficient for preterm neonates with a birth-weight of around 0.5 kg. [ABSTRACT FROM AUTHOR]

A rapid and accurate method to identify severe sepsis patients at high risk of death is critically needed for clinical practice. In a recent study, the concentration of cell-free DNA (cfDNA) in blood was found to be a prognostic indicator for ICU mortality in patients with severe sepsis. However, current DNA quantification techniques are time-consuming and involve extensive sample preparation. In this paper, we demonstrate a low-cost microfluidic device capable of rapid quantification of cfDNA in a small droplet (＜10 μl) of blood plasma and whole blood in 5 min using only electrical power. The cfDNA in samples is selectively labeled by PicoGreen and is extracted and concentrated by electrophoresis into a gel by application of a DC potential of 9 V. This device has potential as a prognostic tool for early and rapid assessment of septic patients. [ABSTRACT FROM AUTHOR]

A modified poly(dimethyl siloxane) (PDMS) material is under development for use in an extracorporeal microfluidic blood oxygenator designed as an artificial placenta to treat newborn infants suffering from severe respiratory insufficiency. To prevent thrombosis triggered by blood-material contact, an antithrombin–heparin (ATH) covalent complex was coated on PDMS surface using polydopamine (PDA) as a “bioglue”. Experiments using radiolabelled ATH showed that the ATH coating on PDA-modified PDMS remained substantially intact after incubation in plasma, 2% SDS solution, or whole blood over a three day period. The anticoagulant activity of the ATH-modified surfaces was also demonstrated: in contact with plasma the ATH-coated PDMS was shown to bind antithrombin (AT) selectively from plasma and to inhibit clotting factor Xa. It is concluded that modification of PDMS with polydopamine and ATH shows promise as a means of improving the blood compatibility of PDMS and hence of the oxygenator device. [ABSTRACT FROM AUTHOR]

This paper reports the development of microfluidic oxygenator (MFO) units designed for a lung assist device (LAD) for newborn infants. This device will be connected to the umbilical vessels like the natural placenta and provide gas exchange. The extracorporeal blood flow is only driven by the pressure difference between the umbilical artery and vein without the use of external pumps. The LAD is designed for use in ambient air (∼21% of 760 mmHg). The main focus of this paper is the presentation of the development of the MFO units testing various membrane materials with human blood to enhance gas exchange and in the design of fluidic inlets to lower the pressure drop across the oxygenator. Four different membranes, including thin film PDMS, porous PDMS, and two different pore size porous polycarbonate membranes are compared in this study. Among them, the microfluidic oxygenator with porous PDMS membrane has the highest gas exchange rate of 1.46 μL min−1 cm2 for oxygen and 5.27 μL min−1 cm2 for carbon dioxide and performs better than a commercial hollow fiber-based oxygenator by 367 and 233%, respectively. A new tapered inlet configuration was designed to reduce the pressure drop across the oxygenator and showed a further 57% improvement over the traditional perpendicular inlet configuration. [ABSTRACT FROM AUTHOR]

Protein adsorption on PDMS surfaces poses a significant challenge in microfluidic devices that come into contact with biofluids such as blood. Polyurethane (PU) is often used for the construction of medical devices, but despite having several attractive properties for biointerfacing, it has not been widely used in microfluidic devices. In this work we developed two new fabrication processes for making thin, transparent and flexible PU-based microfluidic devices. Methods for the fabrication and bonding of microchannels, the integration of fluidic interconnections and surface modification with hydrophilic polyethylene oxide (PEO) to reduce protein adsorption are detailed. Using these processes, microchannels were produced having high transparency (96% that of glass in visible light), high bond strength (326.4 kPa) and low protein adsorption (80% reduction in fibrinogen adsorption vs. unmodified PDMS), which is critical for prevention of fouling. Our findings indicate that PEO modified PU could serve as an effective alternative to PDMS in blood contacting microfluidic applications.

Cell based screening assays are increasingly used in drug discovery due to the physiological significance of the results and high content information obtained from them. Miniaturization of this format, currently carried out in microwell plates, is at its limit due to increased unnatural interaction of cells with walls inside micro-wells. In order to overcome this limitation, we present a new format for dynamically controlled, precise, spatial and temporal dosing of a continuous cell culture layer, using microfluidics. The device consists of a micropatterned nanoporous membrane layer that allows specific spatial locations in the continuous gel layer above, to be chemically addressed by external electric field through a microfluidic network below it. We demonstrate that the control of electric field across the nanoporous membrane leads to extremely precise dosing (approximately 50 microg accuracy). Spot sizes of 200 microm to 6 mm in diameter and inter-spot distances of 0.4-10 mm have been obtained. Microarray spot densities of 156 spots/cm(2) were obtained, which is five times higher than the densities used in current cell based assays. The capability of this method in handling small molecules, proteins and drugs is also demonstrated. This format of spatial dosing of continuous cell culture will enable further miniaturization of cell based assays and aid in high-throughput high-content screening.

We present a novel PDMS-based microinjection system in a microfluidic format with precise electroosmotic dosage control. The device architecture is fully scalable and enables high-throughput microinjections with integrated pre- and post-processing operations. The injection mechanism greatly simplifies current methods as only a single degree of freedom is required for injections. The injections are performed inside a fully enclosed channel by an integrated microneedle. Actuation of the needle is achieved by the compliant deformation of the channel structure by an external actuator. Reagent transport is achieved using electroosmotic flow (EOF) which provides non-pulsating flow and precise electrical dosage control. The potentials used for injections were between 5 V-25 V. The electrical properties and flow rates for the device were characterized for Zebrafish embryos and Rhodamine B and Methylene blue in pH 10 buffer solution. We also propose a method to enable precise individual dosing of embryos using direct electrical feedback. Additionally, we show that electrical feedback can be used to verify the location of the needle inside the injection target. A preliminary viability study of our device was conducted using Zebrafish (Danio rerio) embryos. The study involved the injection of ultrapure water into the embryos in an E3 buffer, and resulted in embryos that showed normal development at 48 hours.