Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.

Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip

Microfluidics is an emerging field that has given rise to a large number of scientific and technological developments over the last few years. This review reports on the use of various materials, such as silicon, glass and polymers, and their related technologies for the manufacturing of simple microchannels and complex systems. It also presents the main application fields concerned with the different technologies and the most significant results reported by academic and industrial teams. Finally, it demonstrates the advantage of developing approaches for associating polymer technologies for manufacturing of fluidic elements with integration of active or sensitive elements, particularly silicon devices.

https://iopscience.iop.org/article/10.1088/0960-1317/17/5/R01/pdf

Lab-on-chip technologies: making a microfluidic network and coupling it into a complete microsystem : a review

Microfluidics is an evolving scientific field with immense commercial potential: analytical applications, such as biochemical assay development, biochemical analysis and biosensors as well as chemical synthesis applications essentially require microfluidics for sample handling, treatment or readout. A number of techniques are available to create microfluidic structures today. On industrial scale replication techniques such as injection molding are the gold standard whereas academic research mostly focuses on replication by casting of soft elastomers such as polydimethylsiloxane (PDMS). Both of these techniques require the creation of a replication master thus creating the microfluidic structure only in the second process step—they can therefore be termed two-(or multi-)step manufacturing techniques. However, very often the number of pieces to be created of one specific microfluidic design is low, sometimes even as low as one. This raises the question if two-step manufacturing is an appropriate choice, particularly if short concept-to-chip times are required. In this case one-step manufacturing techniques that allow the direct creation of microfluidic structures from digital three-dimensional models are preferable. For these processes the number of parts per design is low (sometimes as low as one), but quick adaptation is possible by simply changing digital data. Suitable techniques include, among others, maskless or mask based stereolithography, fused deposition molding and 3D printing. This work intends to discuss the potential and application examples of such processes with a detailed view on applicable materials. It will also point out the advantages and the disadvantages of the respective technique. Furthermore this paper also includes a discussion about non-conventional manufacturing equipment and community projects that can be used in the production of microfluidic devices.

/pdf/let-there-be-chip-towards-rapid-prototyping-of-microfluidic-3yd1tiia54.pdf

Let there be chip—towards rapid prototyping of microfluidic devices: one-step manufacturing processes

Significant progress in the development of miniaturized microfluidic systems has occurred since their inception over a decade ago. This is primarily due to the numerous advantages of microchip analysis, including the ability to analyze minute samples, speed of analysis, reduced cost and waste, and portability. This review focuses on recent developments in integrating electrochemical (EC) detection with microchip capillary electrophoresis (CE). These detection modes include amperometry, conductimetry, and potentiometry. EC detection is ideal for use with microchip CE systems because it can be easily miniaturized with no diminution in analytical performance. Advances in microchip format, electrode material and design, decoupling of the detector from the separation field, and integration of sample preparation, separation, and detection on-chip are discussed. Microchip CEEC applications for enzyme/immunoassays, clinical and environmental assays, as well as the detection of neurotransmitters are also described.

Recent developments in electrochemical detection for microchip capillary electrophoresis

Capacitively coupled contactless conductivity detection (C4D) is presented in a progressively detailed approach. Through different levels of theoretical and practical complexity, several aspects related to this kind of detection are addressed, which should be helpful to understand the results as well as to design a detector or plan experiments. Simulations and experimental results suggest that sensitivity depends on: 1) the electrolyte co-ion and counter-ion; 2) cell geometry and its positioning; 3) operating frequency. Undesirable stray capacitance formed due to the close placement of the electrodes is of great importance to the optimization of the operating frequency and must be minimized.

Understanding Capacitively Coupled Contactless Conductivity Detection in Capillary and Microchip Electrophoresis. Part 1. Fundamentals

Microfluidic lab-on-a-chip systems based on polymers - fabrication and application

The detection of ionic species in a polymeric planar electrophoresis device by contactless conductivity measurement is described. To our knowledge this is the first report of such measurements carried out with external electrodes which are part of the holder rather than the separation chip itself. The approach allows the use of bare devices as used for optical measurements, which greatly simplifies the method. The use of a sine wave of 100 kHz of a high amplitude of 500 V for cell excitation assures high sensitivity which is demonstrated with electropherograms for alkali and heavy metal ions as well as inorganic anions and carboxylates at concentrations between 10 and 50 µM. The determination of underivatized amino acids was also possible by using a buffer in the alkaline region where these species are present in anionic form. Detection limits were found to be in the order of 1–5 µM for the inorganic ions and between about 5 and 50 µM for the organic species.

High-voltage contactless conductivity-detection for lab-on-chip devices using external electrodes on the holder

Two important challenges of the rapid development of microfluidic chip systems are addressed in this paper: 1) new polymer materials and technologies for chip preparation and 2) a label-free method for analyte detection in microchannels. One of the general pacemakers in lab-on-a-chip concepts, capillary electrophoresis (CE) in chip format, was used as workhorse for demonstration. CE chips were fabricated and characterized using polymers such as PMMA, polystyrene and polycarbonate, cycloolefine copolymer, and for the first time, the outstanding high-performance polymer polyether ether ketone (PEEK). Especially for one of the most critical steps in microchannel preparation, bonding of the cover layer to the microstructured substrate, an advanced plasma preconditioning process has been developed. An electrical detection method, capacitively coupled contactless conductivity measurement (CCD), was transferred to the chip level. A high signal-to-noise ratio was obtained by using sputtered thin-film electrodes. It was additionally improved by the very thin channel cover layer thickness, which could be easily obtained by polymer technology. CCD was used for analyte detection near the outlet of the CE separation channel. Further, to demonstrate generally the benefit of CCD for microfluidic flow control, measurement electrodes were positioned at the CE chip injection cross to monitor the reliability of the sophisticated injection processes. A completely miniaturized CE device (ldquoMinCErdquo), was developed for low cost application. Potential applications were demonstrated on selected typical examples: for in situ food analysis, the determination of saccharides in beverages, for medical point-of-care diagnostics, the quantitative determination of antidepressant lithium in blood serum, and for bio analytics, the detection of proteinogenic amino acids. Biological macro molecules-in particular, for life sciences fundamental DNA-have not been in focus of contactless conductivity measurements until now. However, it was possible for the first time to detect DNA highly sensitive by conductivity measurement. The extremely low detection limits achieved are competitive with laser induced fluorescence (LIF) in commercial CE-chip-devices and could provide a highly cost-efficient alternative.

Polymer Lab-on-a-Chip System With Electrical Detection

The rapid manufacturing of functional capillary electrophoresis (CE) chips made of polymethylmethacrylate (PMMA) based on laser processing technologies including structuring, surface functionalization and packaging was investigated. CO2 laser-assisted micro-patterning was demonstrated to have a great potential for the fabrication of micro-channel devices and the production capability of CO2 laser processes has been extended to micro-channels less than 30 μm width. A high reproducibility of micro-channel geometry was attained. The average deviation between the fabricated cross-section areas and the desired cross-section areas of micro-channels was better than 3%. The packaging of these micro-structured transparent polymers was successfully established with a laser transmission welding technique using high-power diode laser radiation. CE-chips with channel widths of 150, 100 and 50μm were fabricated and electro-analytically characterized. For this purpose high frequency contactless conductivity detection (CCD) was established. Detection of small ions (Li+, Na+, and K+) with concentrations down to 0.1 × 10−3 mol/l was performed. Analytical results compare well to those obtained by conventional hot embossing and thermal welding. Furthermore, UV-assisted surface modification can be used to influence the micro-analytical performance. The pattern qualities and analytical results show that laser-based technologies have a great potential for application in flexible and cost-efficient production of polymeric microfluidic devices.

Laser patterning and packaging of CCD-CE-Chips made of PMMA

As a contribution to the development of innovative microfluidic lab-on-chip systems, this work presents important results for the practical introduction of capillary electrophoresis (CE) in chip format - in particular with the objective of significant cost reduction. Key contributions are the substitution of conventional substrate glass by polymers and the introduction of contactless conductivity measurement for detection instead of expensive optical methods. In this work CE chips were fabricated and characterized using cost effective polymers such as PMMA, polystyrene and polycarbonate, which are already established in mass production processes, as well as chemically inert and biocompatible high-performance polymers COC and PEEK. By using a new bonding process, PEEK as a near-ideal material, could be used for the first time for microfluidic CE-systems. The principal of contactless conductivity measurement was transferred to chip level and optimized to a high signal-to-noise ratio using sputtered thin film electrodes. Chemical analysis results depend significantly on fluid transport behaviour at the fluid injection cross area. This was investigated by fluorescence microscopy on several different cross geometries. Hydrostatic interfering effects and method based instabilities were shown. As a simple alternative to complex fluorescence microscopy, fluid transport could be optimally observed by conductivity measurement. Measurement electrodes placed at the injection cross area allowed real time quantitative analyses. Thus, interferences and method based instabilities can be acquired and compensated for. For basic experimental investigations, a comprehensive and flexible test setup was developed. In practical application however ease of use, portability and low-priced devices are required. To this end, a completely miniaturized measuring device, the ,,MinCE", was developed. Potential applications were demonstrated on selected typical examples: for in-situ food analysis the determination of organic acids and saccharide in beverages, for medical point-of-care diagnostics the quantitative determination of antidepressant lithium in blood serum and for bio analytics the detection of proteinogenic amino acids.

/pdf/mikrofluidische-ce-systeme-aus-polymeren-mit-elektrischer-1nju80ubp1.pdf

W. Hoffmann

Papers

Microfluidic lab-on-a-chip systems based on polymers - fabrication and application

High-voltage contactless conductivity-detection for lab-on-chip devices using external electrodes on the holder

Polymer Lab-on-a-Chip System With Electrical Detection

Laser patterning and packaging of CCD-CE-Chips made of PMMA

Mikrofluidische CE-Systeme aus Polymeren mit elektrischer Detektion für Life-Science-Anwendungen