Robert Gorkin

Serial siphon valving for centrifugal microfluidic platforms

Today, the focus in microfluidic platforms for diagnostics is on the integration of several analysis steps toward sample-to-answer systems. One of the main challenges to integration is the requirement for serial valving to allow the sequential release of fluids in a temporally and spatially controlled manner. The advantages offered by centrifugal microfluidic platforms make them excellent candidates for integration of biological analysis steps, yet they are limited by the lack of robust serial valving technologies. This is especially true for the majority of centrifugal microfluidic devices that rely on hydrophilic surfaces, where few passive serial valving techniques function reliably. Building on the useful functionality of centrifugal microfluidic siphoning previously shown, a novel serial siphon valve is introduced that relies on multiple, inline siphons to provide for a better controlled, sequential release of fluids. The introduction of this novel concept is followed by an analytical analysis of the device. Proof-of-concept is also demonstrated, and examples are provided to illustrate the range of functionality of the serial siphon valve. The serial siphon is shown to be robust and reproducible, with variability caused by the dependence on contact angle, rotation velocity, and fluidic properties (viz., surface tension) significantly reduced compared to current microfluidic, centrifugal serial valving technologies.

An overview of the suitability of hydrogel-forming polymers for extrusion-based 3D-printing

This review evaluates hydrogel-forming polymers that are suitable for soft tissue engineering with a focus on materials that can be fabricated using additive manufacturing (3D-printing). An overview of the specific material requirements for hydrogel-based tissue engineering constructs is presented. This is followed by an explanation of the various hydrogel-forming polymer classes that includes a detailed examination of material properties that are critical for extrusion printing. Specifically, mechanisms for hydrogel formation, degradation, and biological response, activity and compatibility are explored. A discussion of extrusion printing strategies for printable hydrogel-forming polymers is then presented in conjunction with a list of considerations to guide future tissue engineering developments.

Graphene oxide dispersions: tuning rheology to enable fabrication

Here, we show that graphene oxide (GO) dispersions exhibit unique viscoelastic properties, making them a new class of soft materials. The fundamental insights accrued here provide the basis for the development of fabrication protocols for these two-dimensional soft materials, in a diverse array of processing techniques.

Centrifugal microfluidics for cell analysis.

Over the past two decades, centrifugal microfluidic systems have successfully demonstrated their capability for robust, high-performance liquid handling to enable modular, multi-purpose lab-on-a-chip platforms for a wide range of life-science applications. Beyond the handling of homogeneous liquids, the unique, rotationally controlled centrifugal actuation has proven to be specifically advantageous for performing cell and particle handling and assays. In this review we discuss technologies to implement two important steps for cell handling, namely separation and capturing/counting.

Poly(3,4-ethylenedioxythiophene): Dextran sulfate (PEDOT: DS) - A highly processable conductive organic biopolymer

A novel water-dispersible conducting polymer analogous to poly(3,4-dioxythiophene):polystyrene sulfonate (PEDOT:PSS) has been chemically synthesized in a single reaction in high yield. PEDOT:DS, a new member of the polythiophene family, is composed of a complex between PEDOT and the sulfonated polysaccharide polyanion dextran sulfate. Drop-cast films of aqueous suspensions of the material display a native conductivity of up to 7 ± 1 S cm(-1), increasing to 20 ± 2 S cm(-1) after treatment with ethylene glycol and thermal annealing. Mass ratios of the precursors NaDS and EDOT were varied from 5:1 to 2:1 and a decrease in the NaDS:EDOT ratio produces tougher, less hygroscopic films of higher conductivity. Ultraviolet-visible spectroelectrochemistry yields spectra typical of PEDOT complexes. Cyclic voltammetry reveals that PEDOT:DS is electrochemically active from -1.0 to 0.8 V vs. Ag/Ag(+) in acetonitrile, with similar characteristics to PEDOT:PSS. Water dispersions of PEDOT:DS are successfully processed by drop casting, spray coating, inkjet printing and extrusion printing. Furthermore, laser etching of dried films allows the creation of patterns with excellent definition. To assess the cytotoxicity of PEDOT:DS, L-929 cells were cultured with a polymer complex concentration range of 0.002 to 0.2 g l(-1) in cell culture medium. No significant difference is found between the proliferation rates of L-929 cells exposed to PEDOT:DS and those in plain medium after 96h. However, PEDOT:PSS shows around 25% less cell growth after 4 days, even at the lowest concentration. Taken together, these results suggest PEDOT:DS has exceptional potential as an electromaterial for the biointerface.

A bio-friendly, green route to processable, biocompatible graphene/polymer composites

Graphene-based polymer composites are a very promising class of compounds for tissue engineering scaffolds. However, in general the methods of synthesis are environmentally hazardous and residual toxic materials can affect the biocompatibility significantly. In this paper a simple, scalable, environmentally-friendly, microwave-assisted synthesis is described that results in conducting graphene/polycaprolactone composites that retain the processability and biocompatibility of the pristine polymer without introducing possibly hazardous reducing agents. Composites of polycaprolactone and graphene oxide were synthesised in a single step by the ring-opening polymerisation of e-caprolactone in the presence of dispersed graphene oxide nanosheets under microwave irradiation. The graphene oxide provides a nucleation centre for the crystallisation of the polymer resulting in polymer-functionalised nanosheets. During polymerisation, the graphene oxide was also reduced to conducting graphene. The resulting graphene/polymer composites were comparable to composites prepared by blending previously highly chemically reduced graphene into polycaprolactone, and they could be easily dispersed in a number of solvents or melt extruded for further processing. These three-dimensional melt extruded materials showed excellent biocompatibility and are promising substrates for tissue engineering scaffolds.

Printed ionic-covalent entanglement hydrogels from carrageenan and an epoxy amine

Carrageenan/epoxy amine ionic-covalent entanglement hydrogels were fabricated on a 3D printer. The thermal gel transition behaviour of the biopolymer kappa-carrageenan was exploited to fix the shape of the patterned ink until a covalent polymer network formed by epoxy amine addition chemistry. The printed hydrogels display a work of extension value of 1.4 ± 0.3 MJ m−3.

Fluidic Automation of Nitrate and Nitrite Bioassays in Whole Blood by Dissolvable-Film Based Centrifugo-Pneumatic Actuation

This paper demonstrates the full centrifugal microfluidic integration and automation of all liquid handling steps of a 7-step fluorescence-linked immunosorbent assay (FLISA) for quantifying nitrate and nitrite levels in whole blood within about 15 min. The assay protocol encompasses the extraction of metered plasma, the controlled release of sample and reagents (enzymes, co-factors and fluorescent labels), and incubation and detection steps. Flow control is implemented by a rotationally actuated dissolvable film (DF) valving scheme. In the valves, the burst pressure is primarily determined by the radial position, geometry and volume of the valve chamber and its inlet channel and can thus be individually tuned over an extraordinarily wide range of equivalent spin rates between 1,000 RPM and 5,500 RPM. Furthermore, the vapour barrier properties of the DF valves are investigated in this paper in order to further show the potential for commercially relevant on-board storage of liquid reagents during shelf-life of bioanalytical, ready-to-use discs.

Capillary filling in centrifugally actuated microfluidic devices with dynamically evolving contact line motion

In the present work, we analyze the capillary filling dynamics in centrifugally actuated microfluidic platforms with dynamically evolving contact line motion for wetting fluids. Special attention is devoted to estimate the effects of variable hydraulic resistances over different flow regimes. Dynamics of the meniscus advancement within the rotating microchannel turns out to be typically nonlinear, in tune with the relative instantaneous strengths of the capillary forces, centrifugal forces, and viscous resistances. Detailed dynamical characteristics of the meniscus evolution are obtained from the approximate semianalytical and full-scale numerical solutions, and are found to agree well with the experimental findings on lab-on-a-compact disk arrangements.

Design and fabrication of a COP-based microfluidic chip: Chronoamperometric detection of Troponin T

This work demonstrates the design and fabrication of an all cyclo‐olefin polymer based microfluidic device capable of capturing magnetic beads and performing electrochemical detection in a series of gold electrodes. The size of chip is of a microscope slide and features six independent measuring cells for multianalyte detection purposes. The aim of this work is to show that rapid prototyping techniques can be instrumental in the development of novel bioassays, particularly in clinical diagnosis applications. We show the successful determination of troponin‐T, a cardiac disease marker, in the clinically relevant range of 0.05–1.0 ng/mL. This methodology achieves a detection limit of 0.017 ng/mL in PBS solutions, and is capable of detecting less than 1 ng/mL in a 1:50 human serum dilution.