Tom McCreedy

Fabrication techniques and materials commonly used for the production of microreactors and micro total analytical systems

Abstract Over the last decade, microfabrication techniques have been reported for the production of devices in which fluidic manipulation and component separations of chemical and biological materials can be carried out. The term micro total analytical system (μTAS) is an accepted concept. However, it is perhaps the potential application of microfabricated devices in the wider context that has given added momentum to their development. In this review, the focus will be on the materials and fabrication methods frequently encountered for the production of such devices. Fluidic manipulation is achieved with either hydrostatic displacement pumps such as the syringe pump or electro-osmotic flow, which brings the added advantage of electrophoretic separations.

Rapid prototyping of glass and PDMS microstructures for micro total analytical systems and micro chemical reactors by microfabrication in the general laboratory

A method is presented that permits the microfabrication of glass chips for micro total analytical systems and micro chemical reactors in the general laboratory. The method does not require any specialist facilities, and for the first time provides a reliable and reproducible method for fabricating such devices without access to a clean room. The predictability of the process is achieved by utilising commercially available starting materials.

Interfacing microchip capillary electrophoresis with inductively coupled plasma mass spectrometry for chromium speciation

A microchip based electrophoresis separation system was interfaced with inductively coupled plasma mass spectrometry to provide rapid elemental speciation capabilities. The feasibility of this hyphenated method for elemental speciation was demonstrated by the on-line electrophoretic separation of CrIII and CrVI within 30 s using an 8 cm long separation channel etched in a glass base.

Interfacing a microfluidic electrophoresis chip with inductively coupled plasma mass spectrometry for rapid elemental speciation

A microfluidic chip based electrophoresis system was interfaced with inductively coupled plasma mass spectrometry to provide rapid elemental speciation capabilities. The chip had an 8 cm long, 100 µm wide and 20 µm deep separation channel etched in a serpentine pattern on the glass base plate (30 × 25 × 3 mm). Hydrodynamic sample injection was accomplished by a flow injection mode through an externally controlled gravity pump and a three-way valve. With application of an electric field up to 500 V cm−1, species such as Cr(III) and Cr(VI), Cu(II) and Cu(EDTA)2− were separated in acidic solution within 30 s. The separation of As(III) and As(V) was achieved in an alkaline buffer system by using hydrodynamically modified electroosmotic flow (HMEOF) to control the fluid. The quantification of these species is also reported.

Electric field-induced mobilisation of multiphase solution systems based on the nitration of benzene in a micro reactor

This paper describes the electric field-induced flow characteristics of multiphase solutions in a micro reactor device using the nitration of benzene as a model process. Photolithographic and wet etching techniques were used to fabricate the micro reactor (channels, 200 microns id, 100 microns deep) in a borosilicate glass substrate. The results focus specifically on the flow parameters of reagents/reactants (i.e., voltage, solution concentration and pH ranges and current-voltage relationships) used in this study. The benzene was introduced and mobilised by electroosmotic flow (EOF), as a microemulsion using an appropriate surfactant (sodium dodecyl sulfate), whilst the nitronium ions, produced in situ from mixed H2SO4-HNO3 (the nitrating agent), underwent electrophoretic-induced (electrokinetic) mobility. A co-surfactant, butan-1-ol, was used owing to (a) its relative solubility in the aqueous surfactant solution, (b) its ability to aid the solubilization of benzene, (c) the provision of a water-rich (oil-in-water) rather than oil-rich (water-in-oil) microemulsion system and (d) its lack of significant adverse effects on the EOF. The optimum conditions used for the nitration of benzene within the micro reactor were a run of the microemulsion as main reagent stream, then three 30 s segmented injections of mixed acid, with a 5 s push of the microemulsion into the system after each injection, and then a 60 s stopped-flow reaction time before driving reaction product segments to a collection reservoir.

Microfabricated reactors for on-chip heterogeneous catalysis

Microfabricated devices constructed from glass and polydimethylsiloxane with integral heaters are described, which can be used for heterogeneous catalysis reactions. Sulfated zirconia is used as the catalyst in an open channel reactor, with either a syringe pump or electroosmotic flow being used to deliver the reactants. The results clearly demonstrate that very high conversion efficiencies are possible, however, the thermodynamics of the reactions are the same as in bulk systems. Ethanol and hexanol are dehydrated to ethene and hexene, respectively, with conversion efficiencies approaching 100%, and the esterification of ethanol is investigated. Yields of approximately 30% ethyl acetate are obtained by gas chromatographic analysis. This is the first time such a method for fabricating a catalyst micro reactor has been reported, yet it demonstrates sufficient robustness and resistance to leakage. The use of electroosmotic flow in a heated catalyst reactor is a significant advancement in reactor design.

Tris(2,2'-bipyridine)ruthenium(II) electrogenerated chemiluminescence of alkaloid type drugs with solid phase extraction sample preparation.

An electrogenerated chemiluminescence (ECL) method for the determination of pethidine, atropine, homatropine and cocaine is described. The optimum conditions were found to be similar for all of these compounds although the ECL emission intensity for cocaine was an order of magnitude lower than for pethidine due to their different chemical structures. Linear calibrations were obtained for all the compounds at pH 10 in borate buffer (0.05 mol l-1) at 1.3 V. Limits of detection of 6.8 x 10(-8), 2.2 x 10(-7), 3.2 x 10(-7) and 6.5 x 10(-7) mol l-1, respectively, were achieved for pethidine, atropine, homatropine and cocaine in standard solutions. Solid-phase extraction was used to separate the drugs from their matrix and the method was applied to the determination of spiked urine samples. The limits of quantitation for pethidine, atropine, homatropine and cocaine in urine were 1.0 x 10(-6), 2.0 x 10(-6), 2.0 x 10(-6) and 4.0 x 10(-6) mol l-1, respectively, with recoveries of between 90 and 110%.

Determination of morpholine fungicides using the tris(2,2′-bipyridine) ruthenium(II) chemiluminescence reaction.

Chemiluminescence and electrogenerated chemiluminescence (ECL) methods based on the tris(2,2′-bipyridine) ruthenium(II) chemiluminescence reaction were compared for the analysis of morpholine fungicides. Both methods proved to be sensitive and selective for the determination of dodemorph. In the chemiluminescence system the tris(2,2′-bipyridine) ruthenium(II) was oxidised with Ce(IV) and the flow rate, coil length and pH were optimised by a multivariate method. In the ECL system, the tris(2,2′-bipyridine) ruthenium(II) was oxidised at an aluminium working electrode. The calibration characteristics of the two methods were similar. The linear range was between 2 × 10−7–1 × 10−5 mol l−1 for the chemiluminescence method and 1 × 10−7–3 × 10−5 mol l−1 for the ECL method. The limits of detection were 4.8 × 10−8 mol l−1 for chemiluminescence and 4.4 x10−8 mol l−1 for ECL. A related fungicide tridemorph was also determined by ECL and the linear range for that was between 5 × 10−7 and 5 × 10−5 mol l−1, with a limit of detection of 4.5 × 10−7 mol l−1. An interference study showed that the main interferences for both methods were ascorbic acid and oxalic acid that interfered at the 2 × 10−6 and 1.0 × 10−6 mol l−1 level, respectively. Good recoveries (96–100%) were obtained for the determination of dodemorph on cotton gloves and laboratory coats although a methanol extraction was used for the chemiluminescence method and a water extraction for the ECL method. This was because methanol depressed the ECL signal. A study of dodemorph uptake in barley was also carried out. Although ECL was the more elegant method for analysis it was less tolerant to methanol and this could be a disadvantage if it were required to extract the analyte from the sample.

On-chip catalysis using a lithographically fabricated glass microreactor—the dehydration of alcohols using sulfated zirconia

A heated microreactor has been fabricated for heterogeneous catalysis, employing channels microfabricated in glass using photolithography and wet chemical etching; the demonstration reaction is the dehydration of alcohols.

Microfabricated bioreactor chips for immobilised enzyme assays

A microfabricated device is reported that has been designed to permit the in situ packing of a section of channel with enzyme immobilised onto controlled pore glass (CPG). It is fabricated from glass and polydimethylsiloxane and to prevent dead volumes, has dedicated channels for packing the reactor. The device has the advantage of being simple in design, the flow through enzyme reactor channel being simply a widened section of the analyte channel. The system is suitable for both hydrodynamic and electro-osmotic pumping, and is designed such that when the packing is exhausted it can be repacked. Controlled pore glass provides a reproducible none swelling, high porosity medium onto which the enzyme could be immobilised. The large particle size meant that it was vital to optimise the immobilisation procedure in order to achieve acceptable enzyme activity. The microfabricated device was developed with two enzymes of different molecular masses; alkaline phosphatase and xanthine oxidase. The pore size of the CPG was found to be very important for xanthine oxidase, where the 697 A pore size (120–200 mesh) CPG was found to give the highest activity (18–20% activity retained after immobilisation). The microfabricated device was used for the assay of p-nitrophenyl phosphate and hypoxanthine with spectrophotometric detection at 405 and 470 nm, respectively. The limits of detection were 5 and 8 M, respectively.