Integrated Lithographic Molding for Microneedle-Based Devices

This paper presents a new fabrication method consisting of lithographically defining multiple layers of high aspect-ratio photoresist onto preprocessed silicon substrates and release of the polymer by the lost mold or sacrificial layer technique, coined by us as lithographic molding. The process methodology was demonstrated fabricating out-of-plane polymeric hollow microneedles. First, the fabrication of needle tips was demonstrated for polymeric microneedles with an outer diameter of 250 mum, through-hole capillaries of 75-mum diameter and a needle shaft length of 430 mum by lithographic processing of SU-8 onto simple v-grooves. Second, the technique was extended to gain more freedom in tip shape design, needle shaft length and use of filling materials. A novel combination of silicon dry and wet etching is introduced that allows highly accurate and repetitive lithographic molding of a complex shape. Both techniques consent to the lithographic integration of microfluidic back plates forming a patch-type device. These microneedle-integrated patches offer a feasible solution for medical applications that demand an easy to use point-of-care sample collector, for example, in blood diagnostics for lithium therapy. Although microchip capillary electrophoresis glass devices were addressed earlier, here, we show for the first time the complete diagnostic method based on microneedles made from SU-8

Direct measurement of lithium in whole blood using microchip capillary electrophoresis with integrated conductivity detection

The direct measurement of lithium in whole blood is described. Using microchip capillary electrophoresis (CE) with defined sample loading and applying the principles of column coupling, alkali metals were determined in a drop of whole blood. Blood collected from a finger stick was mixed with anticoagulant and transferred onto the chip without extraction or removal of components. The electrokinetic transport of red blood cells inside the channels was studied to find sample loading conditions suitable for the analysis of lithium without injecting cells into the separation channel. Both bare glass chips and chips coated with polyacrylamide were used showing the behavior of the cells under different electroosmotic flow conditions. In serum a detection limit for lithium of 0.4 mmol/L was reached. Proteins quickly contaminated untreated chip surfaces but devices with coating gave reproducible electropherograms. In addition, potassium and sodium were also detected in the same separation run. To our knowledge, this is the first device to directly measure ions in whole blood with the use of capillary zone electrophoresis on a microchip

Rapid inorganic ion analysis using quantitative microchip capillary electrophoresis

Rapid quantitative microchip capillary electrophoresis (CE) for online monitoring of drinking water enabling inorganic ion separation in less than 15s is presented. Comparing cationic and anionic standards at different concentrations the analysis of cationic species resulted in non-linear calibration curves. We interpret this effect as a variation in the volume of the injected sample plug caused by changes of the electroosmotic flow (EOF) due to the strong interaction of bivalent cations with the glass surface. This explanation is supported by the observation of severe peak tailing. Conducting microchip CE analysis in a glass microchannel, optimized conditions are received for the cationic species K+, Na+, Ca2+, Mg2+ using a background electrolyte consisting of 30 mmol/L histidine and 2-(N-morpholino)ethanesulfonic acid, containing 0.5 mmol/L potassium chloride to reduce surface interaction and 4 mmol/L tartaric acid as a complexing agent resulting in a pH-value of 5.8. Applying reversed EOF co-migration for the anionic species Cl-, SO42- and HCO3- optimized separation occurs in a background electrolyte consisting of 10 mmol/L 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and 10 mmol/L HEPES sodium salt, containing 0.05 mmol/L CTAB (cetyltrimethylammonium bromide) resulting in a pH-value of 7.5. The detection limits are 20 mu mol/L for the monovalent cationic and anionic species and 10 mu mol/L for the divalent species. These values make the method very suitable for many applications including the analysis of abundant ions in tap water as demonstrated in this paper. (c) 2006 Elsevier B.V. All rights reserved. \u

Mild and Selective C-H Activation of COC Microfluidic Channels Allowing Covalent Multifunctional Coatings

Plastics, such as cyclic olefin copolymer (COC), are becoming an increasingly popular material for microfluidics. COC is used, in part, because of its (bio)-chemical resistance. However, its inertness and hydrophobicity can be a major downside for many bioapplications. In this paper, we show the first example of a surface-bound selective C-H activation of COC into alcohol C-OH moieties under mild aqueous conditions at room temperature. The nucleophilic COC-OH surface allows for subsequent covalent attachments, such as of a H-terminated silane. The resulting hybrid material (COC-Si-H) was then modified via a photolithographic hydrosilylation in the presence of ω-functionalized 1-alkenes to form a new highly stable, solvent-resistant hybrid surface.</p

Microchip capillary electrophoresis for point-of-care analysis of lithium

Background: Microchip capillary electrophoresis (CE) is a promising method for chemical analysis of complex samples such as whole blood. We evaluated the method for point-of-care testing of lithium. \ud Methods: Chemical separation was performed on standard glass microchip CE devices with a conductivity detector as described in previous work. Here we demonstrate a new sample-to-chip interface. Initially, we took a glass capillary as a sample collector for whole blood from a finger stick. In addition, we designed a novel disposable sample collector and tested it against the clinical standard at the hospital (Medisch Spectrum Twente). Both types of collectors require < 10 mu L of test fluid. The collectors contain an integrated filter membrane, which prevents the transfer of blood cells into the microchip. The combination of such a sample collector with microchip CE allows point-of-care measurements without the need for off-chip sample treatment. This new on-chip protocol was verified against routine lithium testing of 5 patients in the hospital.\ud \ud Results: Sodium, lithium, magnesium, and calcium were separated in < 20 s. The detection limit for lithium was 0.15 mmol/L.\ud \ud Conclusions: The new microchip CE system provides a convenient and rapid method for point-of-care testing of electrolytes in serum and whole blood. (c) 2007 American Association for Clinical Chemistry\ud \u

Tailor-made resealable micro(bio)reactors providing easy integration of in situ sensors

Viefhues M, Sun S, Valikhani D, et al. Tailor-made resealable micro(bio)reactors providing easy integration of in situ sensors. Journal of Micromechanics and Microengineering. 2017;27(6): 065012

Elasto-Tweezers: a novel platform for high-precision cell elasticity measurements

Knust S, Sischka A, Milting H, et al. Elasto-Tweezers: a novel platform for high-precision cell elasticity measurements. In: Micro TAS 2018, Kaohsiun, Taiwan. 2018

A Spring in Performance: Silica Nanosprings Boost Enzyme Immobilization in Microfluidic Channels

Enzyme microreactors are important tools of miniaturized analytics and have promising applications in continuous biomanufacturing. A fundamental problem of their design is that plain microchannels without extensive static internals, or packings, offer limited exposed surface area for immobilizing the enzyme. To boost the immobilization in a manner broadly applicable to enzymes, we coated borosilicate microchannels with silica nanosprings and attached the enzyme, sucrose phosphorylase, via a silica-binding module genetically fused to it. We showed with confocal fluorescence microscopy that the enzyme was able to penetrate the ∼70 μm-thick nanospring layer and became distributed uniformly in it. Compared with the plain surface, the activity of immobilized enzyme was enhanced 4.5-fold upon surface coating with nanosprings and further increased up to 10-fold by modifying the surface of the nanosprings with sulfonate groups. Operational stability during continuous-flow biocatalytic synthesis of α-glucose 1-phosphate was improved by a factor of 11 when the microreactor coated with nanosprings was used. More than 85% of the initial conversion rate was retained after 840 reactor cycles performed with a single loading of enzyme. By varying the substrate flow rate, the microreactor performance was conveniently switched between steady states of quantitative product yield (50 mM) and optimum productivity (19 mM min^–1) at a lower product yield of 40%. Surface coating with silica nanosprings thus extends the possibilities for enzyme immobilization in microchannels. It effectively boosts the biocatalytic function of a microstructured reactor limited otherwise by the solid surface available for immobilizing the enzyme