Björn Samel

Painless Drug Delivery Through Microneedle-Based Transdermal Patches Featuring Active Infusion

This paper presents the first microneedle-based transdermal patch with integrated active dispensing functionality. The electrically controlled system consists of a low-cost dosing and actuation unit capable of controlled release of liquid in the microliter range at low flow-rates and minimally invasive, side-opened, microneedles. The system was successfully tested in vivo by insulin administration to diabetic rats. Active infusion of insulin at 2 mul/h was compared to passive, diffusion-driven, delivery. Continuous active infusion caused significantly higher insulin concentrations in blood plasma. After a 3-h delivery period, the insulin concentration was five times larger compared to passive delivery. Consistent with insulin concentrations, actively administered insulin resulted in a significant decrease of blood glucose levels. Additionally, insertion and liquid injection was verified on human skin. This study shows the feasibility of a patch-like system with on-board liquid storage and dispensing capability. The proposed device represents a first step towards painless and convenient administration of macromolecular drugs such as insulin or vaccines.

The fabrication of microfluidic structures by means of full-wafer adhesive bonding using a poly(dimethylsiloxane) catalyst

In this work, we present the use of a PDMS (poly(dimethylsiloxane)) curing-agent as the intermediate layer for adhesive full-wafer bonding suitable for fabrication of microfluidic structures. The curing-agent of the two-component silicone rubber (Sylgard 184) is spin coated on a substrate, brought into contact with another PDMS layer and heat cured to create an irreversible seal which is as strong as or even stronger than plasma-assisted PDMS bonding. The maximum bond strength is measured to 800 kPa when bonding together PDMS and silicon. The applicability of the new PDMS adhesive bonding method is verified by means of fabricating microfluidic structures. Using this method allows for wafer-level bonding of PDMS to various materials such as PDMS, glass or silicon and more importantly to selectively bond different layers by using a patterned adhesive bonding technique. Moreover, precise alignment of the structural layers is facilitated since curing is initiated upon heat which is an advantage when fabricating multilayer microfluidic devices.

A Thermally Responsive PDMS Composite and Its Microfluidic Applications

This paper describes a novel composite actuator for controlled liquid actuation in microsystems which is based on a thermally responsive elastomer. The composite actuator consists of expandable microspheres incorporated in a polydimethylsiloxane (PDMS) matrix and entails the merits of both PDMS and expandable microspheres. The main characteristic of the composite actuator is to expand upon heat. The expansion is irreversible and the relative volume increase is measured up to 270% of its original volume after heating to 80 degC. The composite was used to fabricate single-use microfluidic pumps and valves. We show the displacement of liquids in the range of nanoliters even against counter pressures up to 100 kPa. Moreover, liquid flow in microchannels was entirely blocked by means of the integrated valves. The valves can withstand pressures up to 140 kPa. The devices are fabricated using low-cost materials only, and the composite actuator allows using wafer-level processing. The fluidic components based on the novel composite are highly integrable and do not require external actuators

A compact, low-cost microliter-range liquid dispenser based on expandable microspheres

This work presents a new low-cost liquid dispenser for the dispensing of microliters to milliliter volumes. The dispensing mechanism is based on a thermal actuator where highly expandable microsphe ...

CMOS-Integrated Si/SiGe Quantum-Well Infrared Microbolometer Focal Plane Arrays Manufactured With Very Large-Scale Heterogeneous 3-D Integration

We demonstrate infrared focal plane arrays utilizing monocrystalline silicon/silicon-germanium (Si/SiGe) quantum-well microbolometers that are heterogeneously integrated on top of CMOS-based electronic read-out integrated circuit substrates. The microbolometers are designed to detect light in the long wavelength infrared (LWIR) range from 8 to 14 μm and are arranged in focal plane arrays consisting of 384 × 288 microbolometer pixels with a pixel pitch of 25 μm × 25 μm. Focal plane arrays with two different microbolometer designs have been implemented. The first is a conventional single-layer microbolometer design and the second is an umbrella design in which the microbolometer legs are placed underneath the microbolometer membrane to achieve an improved pixel fill-factor. The infrared focal plane arrays are vacuum packaged using a CMOS compatible wafer bonding and sealing process. The demonstrated heterogeneous 3-D integration and packaging processes are implemented at wafer-level and enable independent optimization of the CMOS-based integrated circuits and the microbolometer materials. All manufacturing is done using standard semiconductor and MEMS processes, thus offering a generic approach for integrating CMOS-electronics with complex miniaturized transducer elements.

Low-cost uncooled microbolometers for thermal imaging

Cost efficient integration technologies and materials for manufacturing of uncooled infrared bolometer focal plane arrays (FPA) are presented. The technology platform enables 320x240 pixel resolution with a pitch down to 20 μm and very low NETD. A heterogeneous 3D MEMS integration technology called SOIC (Silicon-On-Integrated-Circuit) is used to combine high performance Si/SiGe bolometers with state-of-the-art electronic read-out-integrated-circuits. The SOIC integration process consists of: (a) Separate fabrication of the CMOS wafer and the MEMS wafer. (b) Adhesive wafer bonding. (c) Sacrificial removal of the MEMS handle wafer. (d) Via-hole etching. (e) Via formation and MEMS device definition. (f) Sacrificial etching of the polymer adhesive. We will present an optimized process flow that only contains dry etch processes for the critical process steps. Thus, extremely small, sub-micrometer feature sizes and vias can be implemented for the infrared bolometer arrays. The Si/SiGe thermistor is grown epitaxially, forming a mono-crystalline multi layer structure. The temperature coefficient of resistance (TCR) is primarily controlled by the concentration of Ge present in the strained SiGe layers. TCR values of more than 3%/K can be achieved with a low signal-to-noise ratio due to the mono-crystalline nature of the material. In addition to its excellent electrical properties, the thermistor material is thermally stable up to temperatures above 600 °C, thus enabling the novel integration and packaging techniques described in this paper. Vacuum sealing at the wafer level reduces the overall costs compared to encapsulation after die singulation. Wafer bonding is performed using a Cu-Sn based metallic bonding process followed by getter activation at ≥350 °C achieving a pressure in the 0.001 mbar range. After assembling, the final metal phases are stable and fully compatible with hightemperature processes. Hermeticity over the product lifetime is accomplished by well-controlled electro-deposition of metal layers, optimized bonding parameters and a suitable bond frame design.

Expandable microspheres incorporated in a PDMS matrix: a novel thermal composite actuator for liquid handling in microfluidic applications

In this study a novel actuator concept based on expandable microspheres incorporated in a PDMS matrix is presented. Merging the merits of the two substances gives the resulting composite material novel application possibilities as well as novel performance and processing properties. The expansion behavior of the composite was investigated and a maximum volume change of 270% of its original volume was measured after heating to 80/spl deg/C. Applying a heat treatment to the composite shows its capability of filling out deep voids. The composite shows very good applicability as embedded actuator and may be appropriate for various applications. Furthermore, the applicability of the composite for replica molding has been demonstrated by creating inverse replicated features in the cured composite. We show the investigation of fabrication, expansion and application techniques by means of a novel actuator concept for liquid handling.

Wafer-Level Process for Single-Use Buckling-Film Microliter-Range Pumps

In this paper, we present the development of disposable single-use microfluidic pumps entirely based on a straightforward wafer-level fabrication scheme, which allows for precise integrated active dosing in the microliter range. To accomplish stroke-lengths needed for microliter-range applications, we utilize a new method of bending of a unimorph-composite-actuator film. The unimorph composite actuator consists of a temperature-sensitive silicone elastomer composite, i.e., polydimethylsiloxane, with incorporated expandable microspheres. The fabricated micropumps successfully demonstrated precise liquid-volume control, both at low and high flow rates, and show a standard deviation of 6.7% for consecutive pump experiments. Moreover, the method of fluorescent thermometry was used to measure the thermal load on liquid volumes dispensed with the micropumps. The liquid temperature reaches a maximum of 50degC during the operation. The presented fully integrated single-use micropumps are electrically controllable, do not require external means for liquid actuation, are made of low-cost materials only, and might potentially be used in drug-delivery applications.

Low cost device for precise microliter range liquid dispensing

In this work we present the fabrication and testing of a thermally actuated one-shot liquid dispenser, which actuation is based on highly expandable microspheres. We show an uncomplicated, fully functional, low cost device for use in medical disposables, e.g. transdermal systems based on microneedles. All device components are made out of low cost materials and fabrication processes have the potential for high volume batch manufacturing. The device utilizes the properties of the expandable microspheres to form a heat insulating layer to the delivered liquid. Moreover, it does not require any feed-back or complicated flow metering. The device was successfully tested showing a mean dispensed liquid of 101 /spl mu/l with a relative standard deviation of 3.2% and with a maximum temperature of 59/spl deg/C in the liquid during actuation. No back-flow was observed for the device.

Toward 17µm pitch heterogeneously integrated Si/SiGe quantum well bolometer focal plane arrays

Most of todays commercial solutions for un-cooled IR imaging sensors are based on resistive bolometers using either Vanadium oxide (VOx) or amorphous Silicon (a-Si) as the thermistor material. Despite the long history for both concepts, market penetration outside high-end applications is still limited. By allowing actors in adjacent fields, such as those from the MEMS industry, to enter the market, this situation could change. This requires, however, that technologies fitting their tools and processes are developed. Heterogeneous integration of Si/SiGe quantum well bolometers on standard CMOS read out circuits is one approach that could easily be adopted by the MEMS industry. Due to its mono crystalline nature, the Si/SiGe thermistor material has excellent noise properties that result in a state-ofthe- art signal-to-noise ratio. The material is also stable at temperatures well above 450°C which offers great flexibility for both sensor integration and novel vacuum packaging concepts. We have previously reported on heterogeneous integration of Si/SiGe quantum well bolometers with pitches of 40μm x 40μm and 25μm x 25μm. The technology scales well to smaller pixel pitches and in this paper, we will report on our work on developing heterogeneous integration for Si/SiGe QW bolometers with a pixel pitch of 17μm x 17μm.