Lab-on-a-Chip turns soft : computer-aided, software-enabled microfluidics design

The current practice of designing microfluidic Lab-on-a-Chip (LoCs) limits reusing designs and makes sharing tasks among researchers difficult. One way to achieve that objective is to borrow best practices from engineering. Also it takes a lot of skills to design LoCs. Design-by-assembly in which a LoC can be designed by configuring, laying out subsystems can help new researchers to develop custom chips. Flexible, reusable, and rapid-prototyping-feasible LoC designs can be achieved by fabricated modular microfluidic blocks. However, challenging problems still persist, which limit the usefulness of prefabricated blocks. We propose software microfluidic modules (SoftMABs) based design technique to solve issues fabricated modules face. By configuring SoftMABs, integrating them, the new assembly of SoftMABs can form a 3D LoC design ready to be prototyped. The proposed method can make designing a complex LoC less challenging, and collaborating among laboratories easier. We created SoftMABs and designed a custom microfluidic chip by assembling SoftMABs like LEGOs, dragging-and-dropping them. Later we reconfigured them - by replacing a SoftMAB with another module - to make a new LoC. We believe this computeraided method is an interesting and useful LoC design technique.

CO2 laser manufacturing of miniaturised lenses for lab-on-a-chip systems

This article describes the manufacturing and characterisation of plano-convex miniaturised lenses using a CO2 laser engraving process in PMMA substrates. The technique allows for lenses to be fabricated rapidly and in a reproducible manner at depths of over 200 µm and for lens diameters of more than 3 mm. Experimental characterisation of the lens focal lengths shows good correlation with theory. The plano-convex lenses have been successfully embedded into capillary microfluidic systems alongside planar microlenses, allowing for a significant reduction of ancillary optics without a loss of detection sensitivity when performing fluorescence measurements. Such technology provides a significant step forward towards the portability of fluorescence- or luminescence-based systems for biological/chemical analysis.

A simple microfluidic chip design for fundamental bioseparation

A microchip pressure-driven liquid chromatographic system with a packed column has been designed and fabricated by using poly(dimethylsiloxane) (PDMS). The liquid chromatographic column was packed with mesoporous silica beads of Ia3d space group. Separation of dyes and biopolymers was carried out to verify the performance of the chip. A mixture of dyes (fluorescein and rhodamine B) and a biopolymer mixture (10 kDa Dextran and 66 kDa BSA) were separated and the fluorescence technique was employed to detect the movement of the molecules. Fluorescein molecule was a nonretained species and rhodamine B was attached onto silica surface when dye mixture in deionized water was injected into the microchannel. The retention times for dextran molecule and BSA molecule in biopolymer separation experiment were 45 s and 120 s, respectively. Retention factor was estimated to be 3.3 for dextran and 10.4 for BSA. The selectivity was 3.2 and resolution was 10.7. Good separation of dyes and biopolymers was achieved and the chip design was verified.

A parametric study of a monolithic microfluidic system for on-chip biomolecular separation

A microfabricated poly(dimethylsiloxane) (PDMS) chip containing channel filled with polymer monolith has been developed for on-chip biomolecule separation. Methacrylate monolithic polymers were prepared by photo-initiated polymerization within the channel to serve as a continuous stationary phase. The monolithic polymer was functionalized with a weak anion-exchange ligand, and key parameters affecting the binding characteristics of the system were investigated. The total binding capacity was unaffected by the flow rate of the mobile phase but varied significantly with changes in ionic strength and pH of the binding buffer. The binding capacity decreased with increasing buffer ionic strength, and this is due to the limited available binding sites for protein adsorption resulting from cationic shielding effect. Similarly, the binding capacity decreased with decreasing buffer pH towards the isoelectric point of the protein. A protein mixture, BSA and ovalbumin, was used to illustrate the capacity of the methacrylate-based microfluidic chip for rapid biomolecule separation.

Chip formation mechanism and machinability of wrought duplex stainless steel alloys

This paper investigates the chip formation mechanism and machinability of two-phase materials, such as, wrought duplex stainless steel alloys SAF 2205 and SAF 2507. SEM and optical microscopic details of the frozen cutting zone and chips revealed that the harder austenite phase dissipates in the advancement of the cutting tool, being effectively squeezed out of the softer ferrite phase. Microhardness profiles reveal correlation in hardness from the workpiece material transitioning to the chip. The tool wear (TiAIN + TiN coated solid carbide twist drill) and machining forces were investigated. Tool wear, was dominantly due to the adhesion process which developed from built-up edge formation, is highly detrimental to the flank face. Flute damage was also observed as a major issue in the drilling of duplex alloys leading to premature tool failure. Duplex 2507 shows higher sensitivity to cutting speed during machining and strain hardening at higher velocity and less machinability due to presence of higher percentage of Ni, Mo and Cr.

Quick chip assay using locked nucleic acid modified epithelial cell adhesion molecule and nucleolin aptamers for the capture of circulating tumor cells

The role of circulating tumor cells (CTCs) in disease diagnosis, prognosis, monitoring of the therapeutic efficacy, and clinical decision making is immense and has attracted tremendous focus in the last decade. We designed and fabricated simple, flat channel microfluidic devices polydimethylsiloxane (PDMS based) functionalized with locked nucleic acid (LNA) modified aptamers (targeting epithelial cell adhesion molecule (EpCAM) and nucleolin expression) for quick and efficient capture of CTCs and cancer cells. With optimized flow rates (10 μl/min), it was revealed that the aptamer modified devices offered reusability for up to six times while retaining optimal capture efficiency (>90%) and specificity. High capture sensitivity (92%) and specificity (100%) was observed in whole blood samples spiked with Caco-2 cells (10-100 cells/ml). Analysis of blood samples obtained from 25 head and neck cancer patients on the EpCAM LNA aptamer functionalized chip revealed that an average count of 5 ± 3 CTCs/ml of blood were captured from 22/25 samples (88%). EpCAM intracellular domain (EpICD) immunohistochemistry on 9 oral squamous cell carcinomas showed the EpICD positivity in the tumor cells, confirming the EpCAM expression in CTCs from head and neck cancers. These microfluidic devices also maintained viability for in vitro culture and characterization. Use of LNA modified aptamers provided added benefits in terms of cost effectiveness due to increased reusability and sustainability of the devices. Our results present a robust, quick, and efficient CTC capture platform with the use of simple PDMS based devices that are easy to fabricate at low cost and have an immense potential in cancer diagnosis, prognosis, and therapeutic planning.

Lab-on-a-chip or chip-in-a-lab: challenges of commercialization lost in translation

Lab-on-a-chip technology has been long envisaged to have tremendous commercial potential, owing to the ability of such devices to encapsulate a full range of laboratory processes in a single instrument and operate in a portable manner, rapidly and at low cost. Devices are believed to have potential in fields ranging across medical diagnostics, environmental sampling and a range of consumer products, however, to date very few devices have attained commercial success. This review examines the challenges relating to the commercialization of lab-on-a-chip technology from fundamental research to mass manufacturing and aims to provide insight to both academics and product development specialists the perceived hindrances to commercialization and a strategy by which future work could be translated into commercial success.

Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles- and drug molecules) as well as high-throughput analyses (e.g., bioassays, detection, and diagnostics). In particular, multiphase microfluidics is a rapidly growing technology and has beneficial applications in various fields including biomedicals, chemicals, and foods. In this review, we first describe the fundamentals and latest developments in multiphase microfluidics for producing biocompatible materials that are precisely controlled in size, shape, internal morphology and composition. We next describe some microfluidic applications that synthesize drug molecules, handle biological substances and biological units, and imitate biological organs. We also highlight and discuss design, applications and scale up of droplet- and flow-based microfluidic devices used for drug discovery and delivery.