Deflection of a Viscoelastic Cantilever under a Uniform Surface Stress: Applications to Static-mode Microcantilever Sensors Undergoing Adsorption

The equation governing the curvature of a viscoelastic microcantilever beam loaded with a uniform surface stress is derived. The present model is applicable to static-mode microcantilever sensors made with a rigid polymer, such as SU-8. An analytical solution to the differential equation governing the curvature is given for a specific surface stress representing adsorption of analyte onto the viscoelastic beam’s surface. The solution for the bending of the microcantilever shows that, in many cases, the use of Stoney’s equation to analyze stress-induced deflection of viscoelastic microcantilevers (in the present case due to surface analyte adsorption) can lead to poor predictions of the beam’s response. It is shown that using a viscoelastic substrate can greatly increase sensitivity (due to a lower modulus), but at the cost of a longer response time due to viscoelasticcreep in the microcantilever. In addition, the effects of a coating on the cantilever are considered. By defining effective moduli for the coated-beam case, the analytical solution for the uncoated case can still be used. It is found that, unlike the case of a silicon microcantilever, the stress in the coating due to bending of a polymer cantilever can be significant, especially for metalcoatings. The theoretical results presented here can also be used to extract time-domain viscoelasticproperties of the polymermaterial from beam response data

Resonant Microcantilevers for the Determination of the Loss Modulus of Thin Polymer Films

The increasing interest in polymer materials creates the need for accurate tools to characterize their mechanical properties. Due to energy dissipation in polymers during deformation, these materials exhibit viscoelastic behavior. Accurate determination of these viscoelastic properties and, more specifically, viscous losses, remains challenging and mainly unknown for thin polymer films. In this paper, a straightforward method to determine the loss modulus of organic materials using resonating microcantilevers has been developed. The extracted results for polyisobutylene show the variation of viscous losses over a large range of frequencies (7-350 kHz)

Regulatory T cells in melanoma revisited by a computational clustering of FOXP3+ T cell subpopulations

CD4+ T cells that express the transcription factor FOXP3 (FOXP3+ T cells) are commonly regarded as immunosuppressive regulatory T cells (Treg). FOXP3+ T cells are reported to be increased in tumour-bearing patients or animals, and considered to suppress anti-tumour immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation, and that some non-Treg FOXP3+ T cells, especially memory-phenotype FOXP3low cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3+ T cells is fundamental for revealing the significance of FOXP3+ T cells in tumour immunity, but the arbitrariness and complexity of manual gating have complicated the issue. Here we report a computational method to automatically identify and classify FOXP3+ T cells into subsets using clustering algorithms. By analysing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3+ subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3+ subpopulations. Interestingly, the computationally-identified FOXP3+ subpopulation included not only classical FOXP3high Treg but also memory-phenotype FOXP3low cells by manual gating. Furthermore, the proposed method successfully analysed an independent dataset, showing that the same FOXP3+ subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3+ T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3+ T cells and Treg

Analysis of Liquid-Phase Chemical Detection Using Guided Shear Horizontal-Surface Acoustic Wave Sensors

Direct chemical sensing in liquid environments using polymer-guided shear horizontal surface acoustic wave sensor platforms on 36° rotated Y-cut LiTaO3 is investigated. Design considerations for optimizing these devices for liquid-phase detection are systematically explored. Two different sensor geometries are experimentally and theoretically analyzed. Dual delay line devices are used with a reference line coated with poly (methyl methacrylate) (PMMA) and a sensing line coated with a chemically sensitive polymer, which acts as both a guiding layer and a sensing layer or with a PMMA waveguide and a chemically sensitive polymer. Results show the three-layer model provides higher sensitivity than the four-layer model. Contributions from mass loading and coating viscoelasticity changes to the sensor response are evaluated, taking into account the added mass, swelling, and plasticization. Chemically sensitive polymers are investigated in the detection of low concentrations (1-60 ppm) of toluene, ethylbenzene, and xylenes in water. A low-ppb level detection limit is estimated from the present experimental measurements. Sensor properties are investigated by varying the sensor geometries, coating thickness combinations, coating properties, and curing temperature for operation in liquid environments. Partition coefficients for polymer-aqueous analyte pairs are used to explain the observed trend in sensitivity for the polymers PMMA, poly(isobutylene), poly(epichlorohydrin), and poly(ethyl acrylate) used in this work

Cantilever-based Resonant Microsensors with Integrated Temperature Modulation for Transient Chemical Analysis

This work introduces a resonant cantilever platform with integrated temperature modulation for real-time chemical sensing. Embedded heaters allow for rapid thermal cycling of individual sensors, thereby enabling real-time transient signal analysis without the need for a microfluidic setup to switch between analyte and reference gases. Compared to traditional mass-sensitive microsensors operating in steady state, the on-chip generation of signal transients provides additional information for analyte discrimination

Transient Analysis of Analyte Desorption Due to Thermal Cycling with Varying Pulse Duration

This paper introduces heating pulse duration modulation on a chemically sensitive, polymer-coated resonant cantilever platform for analyte discrimination during the desorption phase. As in our previous work, the embedded heaters enable real-time measurements of analyte sorption into the polymer film, without the need for traditional valve systems and reference gases [1-2]. This work particularly looks at the effects of varying pulse lengths on the sensor responses, while holding the heating power constant. A model differential equation is developed for the sensor response based on both the device sensitivity and transient response. This model can then be used together with estimation theory for analyte identification and quantification, even in mixtures

Theoretical mass sensitivity of Love wave and layer guided acoustic plate mode sensors

A model for the mass sensitivity of Love wave and layer guided shear horizontal acoustic plate mode (SH–APM) sensors is developed by considering the propagation of shear horizontally polarized acoustic waves in a three layer system. A dispersion equation is derived for this three layer system and this is shown to contain the dispersion equation for the two layer system of the substrate and the guiding layer plus a term involving the third layer, which is regarded as a perturbing mass layer. This equation is valid for an arbitrary thickness perturbing mass layer. The perturbation, Δν, of the wave speed for the two-layer system by a thin third layer of density, ρp and thickness Δh is shown to be equal to the mass per unit area multiplied by a function dependent only on the properties of the substrate and the guiding layer, and the operating frequency of the sensor. The independence of the function from the properties of the third layer means that the mass sensitivity of the bare, two-layer, sensor operated about any thickness of the guiding layer can be deduced from the slope of the numerically or experimentally determined dispersion curve. Formulas are also derived for a Love wave on an infinite thickness substrate describing the change in mass sensitivity due to a change in frequency. The consequences of the various formulas for mass sensing applications are illustrated using numerical calculations with parameters describing a (rigid) poly(methylmethacrylate) wave-guiding layer on a finite thickness quartz substrate. These calculations demonstrate that a layer-guided SH–APM can have a mass sensitivity comparable to, or higher, than that of Love waves propagating on the same substrate. The increase in mass sensitivity of the layer guided SH–APMs over previously studied SH–APM sensors is of significance, particularly for liquid sensing applications. The relevance of the dispersion curve to experiments using higher frequencies or frequency hopping and to experiments using thick guiding layers is discussed

Generalized Model of Resonant Polymer-Coated Microcantilevers in Viscous Liquid Media

Expressions describing the resonant frequency and quality factor of a dynamically driven, polymer-coated microcantilever in a viscous liquid medium have been obtained. These generalized formulas are used to describe the effects the operational medium and the viscoelastic coating have on the device sensitivity when used in liquid-phase chemical sensing applications. Shifts in the resonant frequency are normally assumed proportional to the mass of sorbed analyte in the sensing layer. However, the expression for the frequency shift derived in this work indicates that the frequency shift is also dependent on changes in the sensing layer’s loss and storage moduli, changes in the moment of inertia, and changes in the medium of operation’s viscosity and density. Not accounting for these factors will lead to incorrect analyte concentration predictions. The derived expressions are shown to reduce to well-known formulas found in the literature for the case of an uncoated cantilever in a viscous liquid medium and the case of a coated cantilever in air or in a vacuum. The theoretical results presented are then compared to available chemical sensor data in aqueous and viscous solutions

A Multi-Modal Continuous-Systems Model of a Novel High-Q Disk Resonator in a Viscous Liquid

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ATR-FTIR Spectroscopic Analysis of Sorption of Aqueous Analytes into Polymer Coatings Used with Guided SH-SAW Sensors

Attenuated total internal reflectance Fourier transform infrared (ATR-FTIR) spectroscopy was used for the investigation of sorption of aqueous solutions of analytes into polymer coatings. A series of simple model polymers, such as poly(dimethylsiloxane), poly(epichlorhydrin), and poly(isobutylene), and films and analytes, such as aqueous solutions of ethylbenzene, xylenes, toluene, and nitrobenzene, were used to evaluate the use of ATR-FTIR spectroscopy as a screening tool for sensor development. The ratios of integrated infrared absorption bands provided a simple and efficient method for predicting trends in partition coefficients. Responses of polymer-coated guided shear horizontal surface acoustic wave (SH-SAW) sensor platforms to the series of analytes, using polymer coatings with similar viscoelastic properties, were consistent with ATR-FTIR predictions. Guided SH-SAW sensor responses were linear in all cases with respect to analyte concentration in the tested range. Comparison of ATR-FTIR data with guided SH-SAW sensor data identifies cases where mass loading is not the dominant contribution to the response of the acoustic wave sensor. ATR-FTIR spectra of nitrobenzene, coupled with computational chemistry, provided additional insight into analyte/polymer interactions