We present a novel micromachined fast diffusion based mixing unit for the study of rapid chemical reactions in solution with stopped-flow time resolved Fourier transform infrared spectroscopy (TR-FTIR). The presented approach is based on a chip for achieving lamination of two liquid sheets of 10 microm thickness and approximately 1 mm width on top of each other and operation in the stopped-flow mode. The microstructure is made on infrared transmitting calcium fluoride discs and built up with two epoxy negative photoresist layers and one silver layer in between. Due to the highly laminar flow conditions and the short residence time in the mixer there is hardly any mixing when the two liquid streamlines pass through the mixing unit, which allows one to record a mid-IR transmission spectrum of the analytes prior to reaction. When the flow is stopped, the reactant streams are arrested in the flow-cell and rapidly mixed by diffusion due to the reduced interstream distances and the reaction can be directly followed with hardly any dead time. On the basis of two model reactions-neutralisation of acetic acid with sodium hydroxide as well as saponification of methyl monochloroacetate-the performance of the mixing device was tested revealing proper functioning of the device with a time for complete mixing of less than 100 ms. The experimental results were supported by numerical simulations using computational fluid dynamics (CFD), which allowed a reliable, quantitative analysis of concentration, pressure and flow profiles in the course of the mixing process.

A miniaturized device for simultaneous measurement of glucose and lactate levels was produced by means of photopatterning of enzyme-containing photosensitive membrane precursors. This device shows no cross-talk and a lifetime for both the glucose and the lactate sensors of more than 2 weeks when continuously operated in undiluted bovine serum. Linear response ranges of up to 40 mM for glucose and 25 mM for L-lactate, in combination with 95% response times of < 30 s, were realized. The devices are mass produced by means of thin-film technology on flexible carriers to give catheter-type multisensing devices for in vivo applications. Ex vivo experiments, performed with human volunteers, where the device was continuously operated in an extracorporeal, undiluted, heparinized blood stream for 6 h, gave a correlation of r > 0.98 with respect to laboratory techniques. Subcutaneous measurements of glucose levels in pigs were close to the corresponding blood levels obtained without in vivo calibration.

A new concept for the study of chemical reactions in solution by time-resolved Fourier transform infrared spectroscopy (TR/FT-IR) is presented. The key element of this concept is a micromachined mixing unit for fast and highly reproducible diffusion-based mixing that is incorporated in a flow cell for transmission measurements and operated in the stopped-flow mode. The mixing unit achieves multilamination of two liquid streamlines inside the flow cell. When the flow in both feeding channels is maintained, there is almost no mixing of the liquids, because of the short residence time inside the mixer, hence allowing for the recording of a reference spectrum of the reactants prior to reaction. When the flow is stopped by rapid switching of a dedicated injection valve, highly reproducible diffusion-controlled mixing takes place inside the flow cell so that spectral changes induced by the reaction under investigation can be directly followed. The total volume required for one experiment is ∼ 5 μL, and mixing times achieved so far are in the millisecond range. Factors governing time resolution in this new concept are the time required to stop the flow, the spacing of the individual streamlines, the diffusion coefficients of the reactants involved, and the signal strength of the spectral changes induced by the reaction under study. In this paper, the possibilities and limitations of the new concept are studied with the use of three model reactions, which are an acid-base neutralization reaction, the addition of sulfite to formaldehyde, and the basic hydrolysis of methyl monochloroacetate. In addition, the complete mixing process in the system was studied by computational fluid dynamics (CFD) simulations, which provided valuable insights into details of the mixing process itself as well as confirming the experimental results obtained.

In this paper, we present a technology for the batch-fabrication of fluidic devices which combines polymer and metal layers. The structures are fabricated by means of two-layer lithography and SU-8-based wafer bonding technique. The combination of SU-8 and metal layers allows the fabrication of "2(1/2)"-dimensional fluidic structures. We realized different types of micromixers for the investigation of chemical reactions by time resolved FTIR-spectroscopy, a flow-through-cell for IR-detection in capillary electrophoresis (CE) and a CE device with integrated capillary.

The coupling of Fourier transform infrared (FT-IR) spectroscopy as a new on-line detection principle in capillary electrophoresis (CE) is presented. To overcome the problem of total IR absorption by the fused-silica capillaries that are normally employed in CE separations, a micromachined IR-transparent flow cell was constructed. The cell consists of two IR-transparent CaF2 plates separated by a polymer coating and a titanium layer producing an IR detection window, 150 microm wide and 2 mm long, with a path length of 15 microm. The IR beam was focused on the detection window using an off-axis parabolic mirror in an optical device (made in-house) attached to an external optical port of the spectrometer. The connections between the fused-silica capillaries and the flow cell were made by a small O-ring of UV-curing epoxy adhesive on the sharply cut ends of the capillaries, allowing the capillaries to be easily replaced. Aqueous solutions comprising mixtures of adenosine, guanosine, and adenosine monophosphate were used to test the system's performance. Conventional on-line UV detection was employed to obtain reference measurements of analytes after the IR detection flow cell. The limit of FT-IR detection for all analytes (in absolute amounts) was in the nano- to picogram range corresponding to concentrations in the low-millimolar range.