Performance of thermally excited resonators

A study of electrothermal excitation of micromachined silicon beams is reported. The temperature distribution is calculated as a function of the position of the transducer, resulting in stress in the structure which reduces the resonance frequency. Test samples are realized and measurements of resonance frequency, vibration shape and vibration amplitude are carried out. There is a satisfactory agreement between theory and experiment at small thermal stresses. Near the buckling load we find distinct deviations from theory which are ascribed to mechanical imperfections of the beams

Realization of mechanical decoupling zones for package-stress reduction

The realization of mechanical decoupling zones around a membrane to reduce package stresses is presented. Wet-isotropic etching with a nitric/fluoridic solution (HNO3/HF/H2O) as well as reactive-ion etching (RIE) with a sulphurhexafluoride/oxygen (SF6/O2) plasma are investigated to realize deep circular grooves. The shape of the cross section of the groove, which determines the shape of the decoupling zone, can be controlled using the RIE method by changing the etch conditions. It is shown that a large undercut at low pressures as well as a small undercut at high pressures is possible with a SF6/O2 plasma, leading to round or steep sidewalls of the grooves, respectively. Finally a completed bare structure containing a membrane and a surrounding decoupling zone is presented

Thermally Excited Resonating Membrane Mass Flow Sensor

A mass flow sensor based on the frequency shift of a resonating microstructure is being developed, using a measurement principle of the thermoanemometry type. The sensor is to be applied for mass flows up to 10 standard cubic centimeters per minute (sccm; 10sccm = 0.17 mg s-1), with a high sensitivity, a high resolution and a fast response. Here we report on the first prototype consisting of a 2 μm thick membrane: the temperature elevation of the thermally excited vibrating membrane affects its resonance frequency. The three-dimemsional heat transfer within the membrane and the mass flow is modeled, and expressions are derived for the resonance frequencies of initially curved and stressed membranes. Experiments have been carried out for nitrogen flows of up to 500 sccm passing over thermally excited membranes. Predicted and measured values for the shift of the resonance frequency agree well. The sensitivity of the average temperature elevation to the mass flow is quite small: at 10 sccm the cooling effect of the mass flow is only 0.2% of the heat loss by conduction to the substrate. At a resonance frequency of 5.0 kHz, and an average temperature elevation of the mebrane of 8°C, this still leads to a frequency change of 13 Hz in the mass flow range from zero to 10 sccm. Suggestions are presented for increasing the sensitivity of the sensor

Resonating silicon beam force sensor

A resonating silicon-beam force sensor is being deveoped using micro-machining of silicon and IC-compatible processes. Results are reported here of measurements on the force-to-frequency transfer of bare silicon prototypes. The measurements with forces on the sensor beam up to 0.4 N shows a frequency shift of 3.1 to 5.2 times the unloaded resonance frequency f0(f0 congruent with 3 to 5 kHz), depending on the exact dimensions. Considering these figures, we can predict a frequency shift of 18.3 to 27.6 kHz at the maximum load of 1.0 N for the measured samples. Due to the sample lay-out, a force transfer is present from the externally applied force to the actual pulling force on the sensor beam. Using a simple model to calculate this reduction, we obtain good agreement between the measurements and predictions

Membranes fabricated with a deep single corrugation for package stress reduction and residual stress relief

Thin square membranes including a deep circular corrugation are realized and tested for application in a strain-based pressure sensor. Package-induced stresses are reduced and relief of the residual stress is obtained, resulting in a large pressure sensitivity and a reduced temperature sensitivity. Finite element method simulations were carried out, showing that the pressure-deflection behaviour of the structure is close to that of a circular membrane with clamped edge but free radial motion

A piezoelectric micropump based on micromachining of silicon

The design and realization of two pumps based on micromachining of silicon are described. The pumps, which are of the reciprocating displacement type, comprise one or two pump chambers, a thin glass pump membrane actuated by a piezoelectric disc and passive silicon check valves to direct the flow. Chambers, channels and valves are realized in a silicon wafer by wet chemical etching. The results of mechanical calculations and simulations show good agreement with the actual behaviour of the pumps. It is possible to design pumps having a specific yield and pressure dependence, and which are fail-safe (the flow is blocked while the pump is switched off)

Innate immune checkpoint inhibitors for treatment of Diffuse Large B-cell Lymphoma

Treatment of diffuse large B-cell lymphoma (DLBCL) with so-called innate immune checkpoint inhibitors is a novel immunotherapeutic treatment strategy that holds great promise for the future. In brief, this type of treatment reactivates phagocytes, important initiators of anticancer immunity. However, several issues remain to be addressed in order to optimally exploit checkpoint targeting for treatment of DLBCL. Within this thesis several of those issues are discussed. The most prominent therapeutic target for innate checkpoint inhibitors today is the CD47-SIRPα axis. However, most of the clinically evaluated checkpoint inhibitors targeting this axis, are not tumor selective. In this thesis we discuss several improvements, e.g. tumor selective strategies, combinatory strategies and we designed fusion proteins that inhibit the CD47-SIRPα axis selectively on cancer cells. Next, we identified that high CD47 expression only associates with worse survival in non-germinal center B-cell (GCB) DLBCL patients, one of the two major subtypes of this disease. This implies that maybe not all DLBCL patients are suitable for CD47 blockade. Indeed, lab studies confirmed that only non-GCB cells responded to CD47 checkpoint inhibition. Notably, in contrast to earlier reports we identified that a positive phagocytic signal, SLAMF7, was not a requisite for effective treatment with CD47 checkpoint inhibitors and thus cannot be used to stratify patients for treatment. Finally, we describe a novel innate checkpoint, called CD300a, that may be of therapeutic interest for non-GCB DLBCL patients. Taken together, this thesis describes strategies to improve checkpoint inhibitors targeting the CD47-SIRPα axis, highlights the importance of patient selection and identified a novel innate checkpoint with therapeutic potential for the treatment of non-GCB DLBCL. Finally, we point out that SLAMF7 should not be used as an inclusion criteria for treatment with CD47 blockade

Design considerations for micromechanical sensors using encapsulated built-in resonant strain gauges

This paper describes the various design aspects for micromechanical sensors consisting of a structure with encapsulated built-in resonant strain gauges. Analytical models are used to investigate the effect of device parameters on the behaviour of a pressure sensor and a force sensor. The analyses indicate that the sealing cap can have a strong degrading effect on the device performance if the thicknesses of the cap and of the supporting structure are of the same order of magnitude. A novel design, employing bossed structures, is described, which reduces the design complexity and virtually eliminates the influence of the cap on the sensitivity of the sensor