Non-optical biosensing in lab-on-a-chip systems

This paper presents a review of the recent trends and developments in non-optical biosensing platforms for lab-on- a-chip systems. This includes design considerations and applications of the non-optical biosensing platforms. The paper first categorizes the non-optical biosensors into four groups. The definition of each group together with a review of the reported works associated with the group are given. A performance analysis of different non-optical detection methods is also presented.

Lab-on-a-chip : a component view

Miniaturization is being increasingly applied to biological and chemical analysis processes. Lab-on-a-chip systems are direct creation of the advancement in the miniaturization of these processes. They offer a host of exciting applications in several areas including clinical diagnostics, food and environmental analysis, and drug discovery and delivery studies. This paper reviews lab-on-a-chip systems from their components perspective. It provides a categorization of the standard functional components found in lab-on-a-chip devices together with an overview of the latest trends and developments related to lab-on-a-chip technologies and their application in nanobiotechnology. The functional components include: injector, transporter, preparator, mixer, reactor, separator, detector, controller, and power supply. The components are represented by appropriate symbols allowing designers to present their lab-on-a-chip products in a standard manner. Definition and role of each functional component are included and complemented with examples of existing work. Through the approach presented in this paper, it is hoped that modularity and technology transfer in lab-on-a-chip systems can be further facilitated and their application in nanobiotechnology be expanded.

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.

Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology

Quantification of programmed and accidental cell death provides useful end-points for the anticancer drug efficacy assessment. Cell death is, however, a stochastic process. Therefore, the opportunity to dynamically quantify individual cellular states is advantageous over the commonly employed static, end-point assays. In this work, we describe the development and application of a microfabricated, dielectrophoretic (DEP) cell immobilization platform for the realtime analysis of cancer drug-induced cytotoxicity. Microelectrode arrays were designed to generate weak electro-thermal vortices that support efficient drug mixing and rapid cell immobilization at the delta-shape regions of strong electric field formed between the opposite microelectrodes. We applied this technology to the dynamic analysis of hematopoietic tumor cells that represent a particular challenge for real-time imaging due to their dislodgement during image acquisition. The present study was designed to provide a comprehensive mechanistic rationale for accelerated cell-based assays on DEP chips using real-time labeling with cell permeability markers. In this context, we provide data on the complex behavior of viable vs dying cells in the DEP fields and probe the effects of DEP fields upon cell responses to anticancer drugs and overall bioassay performance. Results indicate that simple DEP cell immobilization technology can be readily applied for the dynamic analysis of investigational drugs in hematopoietic cancer cells. This ability is of particular importance in studying the outcome of patient derived cancer cells, when exposed to therapeutic drugs, as these cells are often rare and difficult to collect, purify and immobilize.

Global and threshold-free transcriptional regulatory networks reconstruction through integrating ChIP-Chip and expression data

Inferring transcriptional regulatory networks from high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed TReNGO (Transcriptional Regulatory Networks reconstruction based on Global Optimization), a global and threshold-free algorithm with simulated annealing for inferring regulatory networks by the integration of ChIP-chip and expression data. Superior to existing methods, TReNGO was expected to find the optimal structure of transcriptional regulatory networks without any arbitrary thresholds or predetermined number of transcriptional modules (TMs). TReNGO was applied to both synthetic data and real yeast data in the rapamycin response. In these applications, we demonstrated an improved functional coherence of TMs and TF (transcription factor)- target predictions by TReNGO when compared to GRAM, COGRIM or to analyzing ChIP-chip data alone. We also demonstrated the ability of TReNGO to discover unexpected biological processes that TFs may be involved in and to also identify interesting novel combinations of TFs.

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.