Stephan Sylvest Keller

Cantilever-like micromechanical sensors

The field of cantilever-based sensing emerged in the mid-1990s and is today a well-known technology for label-free sensing which holds promise as a technique for cheap, portable, sensitive and highly parallel analysis systems. The research in sensor realization as well as sensor applications has increased significantly over the past 10 years. In this review we will present the basic modes of operation in cantilever-like micromechanical sensors and discuss optical and electrical means for signal transduction. The fundamental processes for realizing miniaturized cantilevers are described with focus on silicon- and polymer-based technologies. Examples of recent sensor applications are given covering such diverse fields as drug discovery, food diagnostics, material characterizations and explosives detection.

Processing of thin SU-8 films

This paper summarizes the results of the process optimization for SU-8 films with thicknesses ≤5 µm. The influence of soft-bake conditions, exposure dose and post-exposure-bake parameters on residual film stress, structural stability and lithographic resolution was investigated. Conventionally, the SU-8 is soft-baked after spin coating to remove the solvent. After the exposure, a post-exposure bake at a high temperature TPEB ≥ 90 °C is required to cross-link the resist. However, for thin SU-8 films this often results in cracking or delamination due to residual film stress. The approach of the process optimization is to keep a considerable amount of the solvent in the SU-8 before exposure to facilitate photo-acid diffusion and to increase the mobility of the monomers. The experiments demonstrate that a replacement of the soft-bake by a short solvent evaporation time at ambient temperature allows cross-linking of the thin SU-8 films even at a low TPEB = 50 °C. Fourier-transform infrared spectroscopy is used to confirm the increased cross-linking density. The low thermal stress due to the reduced TPEB and the improved structural stability result in crack-free structures and solve the issue of delamination. The knowledge of the influence of different processing parameters on the responses allows the design of optimized processes for thin SU-8 films depending on the specific application.

High throughput label-free platform for statistical bio-molecular sensing.

Sensors are crucial in many daily operations including security, environmental control, human diagnostics and patient monitoring. Screening and online monitoring require reliable and high-throughput sensing. We report on the demonstration of a high-throughput label-free sensor platform utilizing cantilever based sensors. These sensors have often been acclaimed to facilitate highly parallelized operation. Unfortunately, so far no concept has been presented which offers large datasets as well as easy liquid sample handling. We use optics and mechanics from a DVD player to handle liquid samples and to read-out cantilever deflection and resonant frequency. Also, surface roughness is measured. When combined with cantilever deflection the roughness is discovered to hold valuable additional information on specific and unspecific binding events. In a few minutes, 30 liquid samples can be analyzed in parallel, each by 24 cantilever-based sensors. The approach was used to detect the binding of streptavidin and antibodies.

Optimized plasma-deposited fluorocarbon coating for dry release and passivation of thin SU-8 cantilevers

Plasma-deposited fluorocarbon coatings are introduced as a convenient method for the dry release of polymer structures. In this method, the passivation process in a deep reactive ion etch reactor was used to deposit hydrophobic fluorocarbon films. Standard photolithography with the negative epoxy-based photoresist SU-8 was used to fabricate polymer structures such as cantilevers and membranes on top of the nonadhesive release layer. The authors identify the plasma density as the main parameter determining the surface properties of the deposited fluorocarbon films. They show that by modifying the pressure during fluorocarbon deposition, the surface free energy of the coating can be tuned to allow for uniform wetting during spin coating of arbitrary thin SU-8 films. Further, they define an optimal pressure regime for the release of thin polymer structures at high yield. They demonstrate the successful release of SU-8 cantilevers and membranes with thicknesses down to 2.3 and 1.7μm respectively, which is a c...

Polymer-filled microcontainers for oral delivery loaded using supercritical impregnation.

In the last years a large variety of drug delivery systems have been developed to improve bioavailability of therapeutics in oral administration. An increasing interest has arisen in reservoir-based microdevices designed for active ingredients like water insoluble compounds and fragile biomolecules. Such microdevices are designed to protect the active ingredient against degradation and deactivation, and to allow cytoadhesion and unidirectional drug release. There are few works which optimize the drug loading step and often therapeutics are dosed in the microdevices through laborious and time consuming procedures. This work proposes an effective loading technique for a poorly soluble model drug in microcontainers, by combining inkjet printing and supercritical fluid impregnation. Well defined quantities of poly(vinyl pyrrolidone) (PVP) solutions are dispensed into microcontainers by inkjet printing with a quasi-no-waste performance. Then ketoprofen is impregnated in the polymer matrix by using supercritical carbon dioxide (scCO2) as loading medium. The amount of polymer is controlled by the volume and the number of droplets of dispensed polymer and drug loading is tuned by varying the impregnation parameters. Compared to solid dispersions of the same drug and polymer, scCO2-impregnated microcontainers exhibit a more reproducible drug loading and a faster dissolution rate of the active compound which allows drug release to be modulated. The combination of these loading techniques potentially allows the high throughput fabrication of microdevices for oral drug delivery with a safe and solvent-free solution.

Spatial confinement can lead to increased stability of amorphous indomethacin

The aim of this study was to investigate whether the physical stability of amorphous indomethacin can be improved by separating the drug material into small units by the use of microcontainers. Crystallisation from the spatially confined amorphous indomethacin in the microcontainers was determined and compared with the crystallisation kinetics of amorphous bulk indomethacin. Amorphous indomethacin in both a bulk form and contained within microcontainers was prepared by melting of bulk or container-incorporated γ-indomethacin, respectively, followed by quench-cooling. Microcontainers of three different sizes (diameters of 73 μm, 174 μm and 223 μm) were used for the confinement of amorphous indomethacin, in order to elucidate whether the size of the microcontainer had an influence on the stability of the amorphous form. Following preparation, all samples were stored at 30 °C and 23% RH. A sample of 100 microcontainers of each size was selected and measured on a Raman microscope over a period of 30 days to ascertain whether the indomethacin in each container was amorphous or crystalline. Over time, a crystallisation number was obtained for the amorphous indomethacin in the microcontainers. The crystallisation numbers from the microcontainers were compared with the crystallisation kinetics of the amorphous bulk indomethacin, as determined by FT-Raman spectroscopy. Comparison of the numeric crystallisation in the microcontainers with the crystallisation kinetics of the amorphous bulk indomethacin showed that spatial confinement of indomethacin led to a significantly lower extent of crystallisation of the amorphous form. In the 174 μm microcontainers, 29.0 ± 2.6% of the amorphous indomethacin crystallised to the stable γ-form over a period of 30 days, whilst 38.3 ± 1.5% of the amorphous indomethacin crystallised in the 223 μm microcontainers. Both these values were significantly different from that observed in the amorphous bulk indomethacin, where 51.0% crystallised to the γ-form after 30 days. Comparing the 174 and 223 μm microcontainers also revealed a significantly greater stabilising effect of the 174μm microcontainers (p-value of 0.0061). Surprisingly, for microcontainers with an inner diameter of 73 μm, no stability improvement was found when compared to amorphous bulk indomethacin. It was observed that the amorphous indomethacin within these containers converted to the α-form of indomethacin (a metastable polymorph) which was unexpected at the storage conditions at 30 °C and 23% RH.

Fabrication of thin SU-8 cantilevers: initial bending, release and time stability

SU-8 cantilevers with a thickness of 2 ?m were fabricated using a dry release method and two steps of SU-8 photolithography. The processing of the thin SU-8 film defining the cantilevers was experimentally optimized to achieve low initial bending due to residual stress gradients. In parallel, the rotational deformation at the clamping point allowed a qualitative assessment of the device release from the fluorocarbon-coated substrate. The change of these parameters during several months of storage at ambient temperature was investigated in detail. The introduction of a long hard bake in an oven after development of the thin SU-8 film resulted in reduced cantilever bending due to removal of residual stress gradients. Further, improved time-stability of the devices was achieved due to the enhanced cross-linking of the polymer. A post-exposure bake at a temperature TPEB = 50 ?C followed by a hard bake at THB = 90 ?C proved to be optimal to ensure low cantilever bending and low rotational deformation due to excellent device release and low change of these properties with time. With the optimized process, the reproducible fabrication of arrays with 2 ?m thick cantilevers with a length of 500 ?m and an initial bending of less than 20 ?m was possible. The theoretical spring constant of these cantilevers is k = 4.8 ? 2.5 mN m?1, which is comparable to the value for Si cantilevers with identical dimensions and a thickness of 500 nm.

Drift study of SU8 cantilevers in liquid and gaseous environments

We present a study of the drift, in terms of cantilever deflections without probe/target interactions, of polymeric SU8 cantilevers. The drift is measured in PBS buffer (pH 7.4) and under vacuum (1mbar) conditions. We see that the cantilevers display a large drift in both environments. We believe this is because the polymer matrix absorbs liquid in one situation whereas it is being degassed in the other. An inhomogeneous expansion/contraction of the cantilever is seen because one surface of the cantilever may still have remains of the release layer from the fabrication. To further study the effect, we coat the cantilevers with a hydrophobic coating, perfluorodecyltrichlorosilane (FDTS). Fully encapsulating the SU8 cantilever greatly reduces the drift in liquid whereas a less significant change is seen in vacuum.

Surface Functionalization of Epoxy‐Resist‐ Based Microcantilevers with Iron Oxide Nanocrystals

Microcantilevers are miniaturized mechanical sensors which pro- vide a specifi c, real-time and label-free detection of bio/molecules and chemical reactions in different environments with a fast response time and low reagent consumption. The typical trans-duction mechanism is based on the cantilever defl ection due to selective physical and chemical processes occurring on one side of the probe surface.

Microscopic four-point probe based on SU-8 cantilevers

A microscopic four-point probe (μ4PP) for resistivity measurements on thin films was designed and fabricated using the negative photoresist SU-8 as base material. The device consists of four microscopic cantilevers, each of them supporting a probe tip at the extremity. The high flexibility of SU-8 ensures a stable electrical point contact between samples and probe tip with all four electrodes even on rough surfaces. With the presented surface micromachining process, μ4PPs with a probe-to-probe spacing of 10–20μm were fabricated. Resistivity measurements on thin Au, Al, and Pt films were performed successfully. The measured sheet resistances differ by less than 5% from those obtained by a commercial macroscopic resistivity meter. Due to the low contact forces (Fcont<10−4N), the μ4PP is suitable to be applied also to fragile materials such as conducting polymers. Here the authors demonstrate the possibility of performing resistivity measurements on 100-nm-thick pentacene (C22H14) films with a sheet resistan...