Multifrequency impedance measurement technique for wireless characterization of microbiological cell cultures.

An impedance measurement system with probe signal frequencies up to 50 kHz with AC-probe voltages below 30 mV rms was integrated for wireless and battery-free monitoring of microbiological cell cultures. The here presented modular design and the use of state-of-the-art components greatly eases adoptions to a wide range of biotechnological applications without the need of bulky LCR-meters or potentiostats. The device had a power consumption of less than 2.5 mA at a 3.3 V single power supply and worked trouble-free within the humid environment of a cell culture incubator. Measurements on lumped RC-elements showed an error of less than 1% for absolute values and less than 1° regarding the phase of the complex impedance. The performance of sensor devices with interdigitated electrode structures for the measurement of adherent cell cultures was tested in the presence of phosphate-buffered saline solution in the humid atmosphere of an incubator for biological cell cultures.

Characterization of a microflow cytometer with an integrated three-dimensional optofluidic lens system.

Flow cytometry is a standard analytical method in cell biology and clinical diagnostics and is widely distributed for the experimental investigation of microparticle characteristics. In this work, the design, realization, and measurement results of a novel planar optofluidic flow cytometric device with an integrated three-dimensional (3D) adjustable optofluidic lens system for forward-scattering∕extinction-based biochemical analysis fabricated by silicon micromachining are presented. To our knowledge, this is the first planar cytometric system with the ability to focus light three-dimensionally on cells∕particles by the application of fluidic lenses. The single layer microfluidic platform enables versatile 3D hydrodynamic sample focusing to an arbitrary position in the channel and incorporates integrated fiber grooves for the insertion of glass fibers. To confirm the fluid dynamics and raytracing simulations and to characterize the sensor, different cell lines and sets of microparticles were investigated by detecting the extinction (axial light loss) signal, demonstrating the high sensitivity and sample discrimination capability of this analysis system. The unique features of this planar microdevice enable new biotechnological analysis techniques due to the highly increased sensitivity.

Time-resolved Fourier transform infrared spectroscopy of chemical reactions in solution using a focal plane array detector.

A Fourier transform infrared (FT-IR) microscope equipped with a single as well as a 64 x 64 element focal plane array MCT detector was used to measure chemical reaction taking place in a microstructured flow cell designed for time-resolved FT-IR spectroscopy. The flow cell allows transmission measurements through aqueous solutions and incorporates a microstructured mixing unit. This unit achieves lamination of the two input streams with a cross-section of 300 x 5 microm each, resulting in fast diffusion-controlled mixing of the two input streams. Microscopic measurement at defined positions along the outlet channel allows time-resolved information of the reaction taking place in the flow cell to be obtained. In this paper we show experimental results on the model reaction between formaldehyde and sulfite. Using the single-point MCT detector, high-quality FT-IR spectra could be obtained from a spot size of 80 x 200 microm whereas the FPA detector allowed recording light from an area of 260 x 260 microm focused on its 64 x 64 detector elements. Therefore, more closely spaced features could be discerned at the expense of a significantly lower signal-to-noise (S/N) ratio per spectrum. Multivariate curve resolution-alternating least squares was used to extract concentration profiles of the reacting species along the outlet channel axis.

Towards biochemical reaction monitoring using FT-IR synchrotron radiation.

A lab-on-a-chip device made of CaF2 windows and SU-8 polymer was used for fluid lamination to achieve rapid mixing of two streamlines with a cross section of 300 x 5 microm each. Time resolved measurements of the induced chemical reaction was achieved by applying constant feeding low flow rates and by on-chip measurement at defined distances after the mixing point. Synchrotron IR microscopic detection was employed for direct and label-free monitoring of (bio)chemical reactions. Furthermore, using synchrotron IR microscopy the measurement spot could be reduced to the diffraction limit, thus maximizing time resolution in the experimental set-up under study. Based on computational fluid dynamic simulations the principle of the set-up is discussed. Experimental results on the basic hydrolysis of methyl chloroacetate proved the working principle of the experimental set-up. First results on the interaction between the antibiotic vancomycin and a tripeptide (Ac2KAA) involved in the build up of the membrane proteins of gram-positive bacteria are presented.

Mid-IR synchrotron radiation for molecular specific detection in microchip-based analysis systems.

Microstructures constructed from SU-8 polymer and produced on CaF(2) base plates have been developed for microchip-based analysis systems used to perform FTIR spectroscopic detection using mid-IR synchrotron radiation. The high brilliance of the synchrotron source enables measurements at spot sizes at the diffraction limit of mid-IR radiation. This corresponds to a spatial resolution of a few micrometers (5-20 microm). These small measurement spots are useful for lab-on-a-chip devices, since their sizes are comparable to those of the structures usually used in these devices. Two different types of microchips are introduced here. The first chip was designed for time-resolved FTIR investigations of chemical reactions in solution. The second chip was designed for chip-based electrophoresis with IR detection on-chip. The results obtained prove the operational functionality of these chips, and indicate the potential of these new devices for further applications in (bio)analytical chemistry.

Integrated flow-cells for novel adjustable sheath flows.

In this paper two integrated flow-cells are presented that can generate novel sheath flows. The flow-cells allow for dynamic orthogonal control of the sample flow dimensions. In addition to this, the sample flow can be freely positioned inside the channel. The flow-cells are attractive, because they are very simple to fabricate and are compatible with the integration of sensors. Experiments have been carried out demonstrating that the sample flow dimensions can be controlled over a wide range; also the results show good agreement with finite element simulation results.

FFT-based analysis of periodic structures in microacoustic devices.

Periodic structures utilized as transducer or reflector elements play an important role in microacoustic wave devices. Such structures can be described using approximate analytical models. However, to obtain the accuracy required for reliable device simulation, numerical methods have to be employed. In this contribution, we present an efficient numerical approach to calculate the dispersion curves associated with microacoustic modes propagating in periodic structures; the method is demonstrated for the case of Love wave modes. The computational efficiency is related to the utilization of the FFT algorithm in a hybrid Method of Moments (MoM)/Mode-Matching analysis. From the obtained dispersion curves, characteristic parameters such as the stopband width can be obtained which can be used in a coupling-of-modes (COM) model of the structure.

Analysis of viscous losses in the chemical interface layer of Love wave sensors.

Love waves have been introduced as highly effective devices for liquid-sensing applications. For chemical sensors, a microacoustic delay line featuring a multilayered waveguide supporting a generalised Love wave mode can be used in an oscillator setup. The top layer of the waveguide is a chemical interface, which selectively adsorbs certain target molecules in the adjacent liquid. The increase in mass density caused by adsorption can be detected as changes in the oscillation frequency. Commonly used interface materials show viscoelastic losses leading to an unwanted damping of the wave. To keep the signal-to-noise ratio high, the total insertion loss of the delay line should be kept as low as possible. Furthermore, it must not exceed a certain value to allow the electronic circuitry to sustain the oscillation. We analyzed the viscoelastic losses, which strongly depend on the frequency being used. By means of the proposed theoretical approach, the maximum thickness of the interface layer can be determined not to exceed the losses that can be handled by the driving electronics.

Substrates for zero temperature coefficient Love wave sensors.

Microacoustic Love wave delay lines show high sensitivity to perturbations such as mass depositions on the wave-guide surface. Furthermore, because of their shear polarization, Love waves are ideally suited for liquid sensing applications. Using a Love wave delay line as feedback element in an oscillator allows the realization of viscosity sensors, and, using a chemical interface, chemical sensors, where the output signal is the oscillation frequency. To achieve a high effective sensitivity, the cross-sensitivity to temperature has to be kept low. We outline the proper choice of a material and especially focus on the influence of crystal cut and the major device design parameters (mass sensitivity and coupling coefficient) on the temperature coefficient of the sensor.

Analysis and optimization of Love wave liquid sensors.

Love wave sensors are highly sensitive microacoustic devices, which are well suited for liquid sensing applications thanks to the shear polarization of the wave. The sensing mechanism thereby relies on the mechanical (or acoustic) interaction of the device with the liquid. The successful utilization of Love wave devices for this purpose requires proper shielding to avoid unwanted electric interaction of the liquid with the wave and the transducers. In this work we describe the effects of this electric interaction and the proper design of a shield to prevent it. We present analysis methods, which illustrate the impact of the interaction and which help to obtain an optimized design of the proposed shield. We also present experimental results for devices that have been fabricated according to these design rules.