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.

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.

A microfluidic system for testing the responses of head and neck squamous cell carcinoma tissue biopsies to treatment with chemotherapy drugs

Tumors are heterogeneous masses of cells characterized pathologically by their size and spread. Their chaotic biology makes treatment of malignancies hard to generalize. We present a robust and reproducible glass microfluidic system, for the maintenance and “interrogation” of head and neck squamous cell carcinoma (HNSCC) tumor biopsies, which enables continuous media perfusion and waste removal, recreating in vivo laminar flow and diffusion-driven conditions. Primary HNSCC or metastatic lymph samples were subsequently treated with 5-fluorouracil and cisplatin, alone and in combination, and were monitored for viability and apoptotic biomarker release ‘off-chip’ over 7 days. The concentration of lactate dehydrogenase was initially high but rapidly dropped to minimally detectable levels in all tumor samples; conversely, effluent concentration of WST-1 (cell proliferation) increased over 7 days: both factors demonstrating cell viability. Addition of cell lysis reagent resulted in increased cell death and reduction in cell proliferation. An apoptotic biomarker, cytochrome c, was analyzed and all the treated samples showed higher levels than the control, with the combination therapy showing the greatest effect. Hematoxylin- and Eosin-stained sections from the biopsy, before and after maintenance, demonstrated the preservation of tissue architecture. This device offers a novel method of studying the tumor environment, and offers a pre-clinical model for creating personalized treatment regimens.

Autonomous capillary microfluidic system with embedded optics for improved troponin I cardiac biomarker detection

 Cardiovascular diseases are the most prevalent medical conditions affecting the modern world, reducing the quality of life for those affected and causing an ever increasing burden on clinical resources. Cardiac biomarkers are crucial in the diagnosis and management of patient outcomes. In that respect, such proteins are desirable to be measured at the point of care, overcoming the shortcomings of current instrumentation. We present a CO2 laser engraving technique for the rapid prototyping of a polymeric autonomous capillary system with embedded on-chip planar lenses and biosensing elements, the first step towards a fully miniaturised and integrated cardiac biosensing platform. The system has been applied to the detection of cardiac Troponin I, the gold standard biomarker for the diagnosis of acute myocardial infarction. The devised lab-on-a-chip device was demonstrated to have 24 pg/ml limit of detection, which is well within the minimum threshold for clinically applicable concentrations. Assays were completed within approximately 7–9 min. Initial results suggest that, given the portability, low power consumption and high sensitivity of the device, this technology could be developed further into point of care instrumentation useful in the diagnosis of various forms of cardiovascular diseases. 2014 Elsevier B.V. All rights reserved.

Apoptosis goes on a chip : advances in the microfluidic analysis of programmed cell death

Recent years have brought enormous progress in cell-based lab-on-a-chip technologies, allowing dynamic studies of cell death with an unprecedented accuracy. As interest in the microfabricated technologies for cell-based bioassays is rapidly gaining momentum, we highlight the most promising technologies that provide a new outlook for the rapid assessment of programmed and accidental cell death and are applicable in drug discovery, high-content drug screening, and personalized clinical diagnostics.

Fabrication of polycarbonate microfluidic devices using a focusing and defocusing methods of CO2 laser system

Fabrication of microfluidic devices has always been a challenging endeavour due to its characteristics and cost involved. Recently, laser ablation using low cost engravers has been exploited for fast and cheap prototyping. In this paper, we explore the various parameters affecting the fabrication of polycarbonate microfluidic channels using CO2 laser ablation. The results show that, by manipulating the focus length of the laser beam, we can achieve good cross sectional profiles with low surface roughness. The results also show that various profiles can be fabricated by changing the laser parameters such as laser power, cutting speed and number of laser pulses.