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

Polymer microfluidic devices

Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

/pdf/point-of-care-diagnostics-status-and-future-5c7xkio6mh.pdf

Point of care diagnostics: Status and future

Molding of micro components from thermoplastic polymers has become a routinely used industrial production process. This paper describes both the more than 30-year-old history and the present state of development and applications. Hot embossing, injection molding, reaction injection molding, injection compression molding, thermoforming, and various types of tool fabrication are introduced and their advantages and drawbacks are discussed. In addition, design considerations, process limitations, and commercially available micro molding machines are presented.

https://iopscience.iop.org/article/10.1088/0960-1317/14/3/R01/pdf

Review on micro molding of thermoplastic polymers

PDMS is enjoying continued and ever increasing popularity as the material of choice for microfluidic devices due to its low cost, ease of fabrication, oxygen permeability and optical transparency. However, PDMS's hydrophobicity and fast hydrophobic recovery after surface hydrophilization, attributed to its low glass transition temperature of less than -120 degrees C, negatively impacts on the performance of PDMS-based microfluidic device components. This issue has spawned a flurry of research to devise longer lasting surface modifications of PDMS, with particular emphasis on microfluidic applications. This review will present recent research on surface modifications of PDMS using techniques ranging from metal layer coatings and layer-by-layer depositions to dynamic surfactant treatments and the adsorption of amphipathic proteins. We will also discuss significant advances that have been made with a broad palette of gas-phase processing methods including plasma processing, sol-gel coatings and chemical vapor deposition. Finally, we will present examples of applications and future prospects of modified PDMS surfaces in microfluidics, in areas such as molecular separations, cell culture in microchannels and biomolecular detection via immunoassays.

Recent developments in PDMS surface modification for microfluidic devices

Design and fabrication of microfluidic devices on polymethylmethacrylate (PMMA) substrates for analytical chemistry and biomedical-related applications using novel microfabrication methods are described. The image of microstructures is transferred from quartz master templates possessing the inverse image of the devices to plastic plates by using hot embossing methods. The microchannels on quartz master templates are formed by the combination of metal etch mask and wet chemical etching of a photomask blank. The micromachined quartz templates can be used repeatedly to replicate cheap and disposable plastic devices. The reproducibility of the hot embossing method is evaluated using 10 channels on different PMMA plastics. The relative standard deviation of the channel profile on the plastic chips is less than 1%. In this study, the PMMA microfluidic chips have been demonstrated as a microcapillary electrophoresis (μ-CE) device for DNA separation and detection. The capability of the fabricated chip for electrophoretic injection and separation is characterized via the analysis of DNA fragments ∅X-174-RF Hae III digest. Experimental results indicate that all of the 11 DNA fragments of the size marker could be identified in less than 2 min with relative standard deviations less than 0.4 and 8% for migration time and peak area, respectively. Moreover, with the use of a near-infrared (IR) dye, fluorescence signals of the higher molecular weight fragments (>603 bp in length) could be detected at total DNA concentrations as low as 0.1 μg/ml. In addition to DNA fragments ∅X-174-RF Hae III digest, DNA sizing of hepatitis C viral (HCV) amplicon is also achieved using microchip electrophoresis on PMMA substrates.

/pdf/microfabricated-plastic-chips-by-hot-embossing-methods-and-eckvh8uglh.pdf

Microfabricated plastic chips by hot embossing methods and their applications for DNA separation and detection

We have demonstrated previously that liver allograft tolerance is associated with the immunosuppressive activity of anti-histone H1 autoreactive antibodies induced in the serum of liver transplantation. Furthermore, we and others have shown that nuclear proteins such as histone H1 and high mobility group box 1 play an important role in maturation of dendritic cells (DCs), although the precise mechanisms are still unknown. In the present study, we focus upon the significance of histone H1 on DCs in terms of the intracellular signalling pathway of DCs. Our immunostaining and immunoblot studies demonstrated that histone H1 was detected in cytoplasm and culture supernatants upon the activation of DCs. Histone H1 blockage by anti-histone H1 antibody down-regulated the intracellular activation of mitogen-activated protein kinases (MAPKs) (p38) and IkappaBalpha of DCs, and inhibited DC activity in the proliferation of CD4+ T cells. On the other hand, the addition of histone H1 without endotoxin stimulation up-regulated major histocompatibility complex class II, the CD80 and CD86 surface markers of DCs and the activation of MAPKs (p38 and extracellular-regulated kinase 1/2) and IkappaBalpha. These results suggest that the translocation of histone H1 from nuclei to cytoplasm and the release of their own histone H1 are necessary for the maturation of DCs and the activation for T lymphocytes.

The role of a nuclear protein, histone H1, on signalling pathways for the maturation of dendritic cells

The present invention provides an integrated microfluidic electrospray chip system and analytical method thereof, characterized in which the proteinase reaction, solid-phase extraction mechanism, electrophoresis and mass spectrometry are integrated into one system. This system allows continuous, fast and on-line detection and identification of a sample, where the sample is firstly hydrolyzed and desalted, and then introduced into the microfluidic electrospray chip to undergo electrophoresis. Finally, the separated sample is introduced into a mass spectrometer by means of electrospray for continuous detection and identification. This system applies mainly in the identification of biochemical substances, such as proteins.

Microfluidic chip system integrated with nano-electrospray interface and method using thereof

The present invention relates to a hydrophilic surface structure of the non-hydrophilic substrate and the manufacturing method for using the same. The hydrophilic substrate surface structure is fabricated by forming an amphiphilic polymer layer, a cross-linked stacking layer, and a hydrophilic layer in sequence on the surface of a non-hydrophilic substrate. For example, the hydrophobic surface of poly(dimethylsiloxane) (PDMS) can be made from hydrophobic to hydrophilic and the hydrophilicity can be retained for a long period of time and resist protein adsorption. The hydrophilic thin films give long term stability to the PDMS surface by resisting hydrophobicity recovery, which is the major problem with PDMS. The disclosed method can further be used in the immobilization of protein and other molecules. This method can also be used for modifying other substrates which suffer problems of surface instability.

Long-term hydrophilic modification of PDMS substrate and method for manufacturing the same

Microfluidic devices were fabricated on poly(methyl methacrylate) (PMMA) substrate using heat embossing method. Results indicated that all of the 11 DNA fragments of the size marker (HaeIII digest of φX174) could be identified in less than 3 minutes with relative standard deviations less than 0.4% and 8% for migration time and peak area, respectively. The characterized microchip was investigated for clinical post-PCR analysis of hepatitis C virus (HCV) using Laser-induced fluorescence. A separation medium composed of 1% HPMC in TBE buffer and 10 µmol/L intercalating dye (TOPRO-3) was demonstrated to resolve the amplicon of HCV with 135 by in length in less than 1.5 minutes with the confidence interval of the migration time less than 1.3%. Analysis of more than 10 patient samples by both the existing method using agarose gel electrophoresis and the current method using microchip electrophoresis showed a 100% correlation. The polymer microchip, with advantages including fast processing time, simple operation, and disposable use, holds great potential for clinical analysis.

Wang-Chou Sung

Papers

Microfabricated plastic chips by hot embossing methods and their applications for DNA separation and detection

The role of a nuclear protein, histone H1, on signalling pathways for the maturation of dendritic cells

Microfluidic chip system integrated with nano-electrospray interface and method using thereof

Long-term hydrophilic modification of PDMS substrate and method for manufacturing the same

Plastic Microchip Electrophoresis for Clinical Applications of DNA Analysis