Nils Hoivik

Recent Developments in Optical Detection Technologies in Lab-on-a-Chip Devices for Biosensing Applications

The field of microfluidics has yet to develop practical devices that provide real clinical value. One of the main reasons for this is the difficulty in realizing low-cost, sensitive, reproducible, and portable analyte detection microfluidic systems. Previous research has addressed two main approaches for the detection technologies in lab-on-a-chip devices: (a) study of the compatibility of conventional instrumentation with microfluidic structures, and (b) integration of innovative sensors contained within the microfluidic system. Despite the recent advances in electrochemical and mechanical based sensors, their drawbacks pose important challenges to their application in disposable microfluidic devices. Instead, optical detection remains an attractive solution for lab-on-a-chip devices, because of the ubiquity of the optical methods in the laboratory. Besides, robust and cost-effective devices for use in the field can be realized by integrating proper optical detection technologies on chips. This review examines the recent developments in detection technologies applied to microfluidic biosensors, especially addressing several optical methods, including fluorescence, chemiluminescence, absorbance and surface plasmon resonance.

Integrated optical microfluidic biosensor using a polycarbazole photodetector for point-of-care detection of hormonal compounds

Abstract. A picogram-sensitive optical microfluidic biosensor using an integrated polycarbazole photodiode is developed. The photodetector is mainly composed of the blend heterojunction of poly [N-9′-heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT) and [6,6]-phenyl C71-butyric acid methyl ester (PC70BM) and the poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) as the hole transport layer. Analyte detection is accomplished via a chemiluminescent immunoassay performed in a poly(dimethylsiloxane)-gold-glass hybrid microchip, on which antibodies were immobilized and chemiluminescent horseradish peroxidase-luminol-peroxide reactions were generated. Enhanced sensor response to the chemiluminescent light is achieved by optimizing the thickness of PCDTBT:  PC70BM and PEDOT:PSS. Using the optimized polycarbazole photodiode for detecting the human thyroid-stimulating hormone as the model target, the integrated biosensor demonstrates an excellent linearity in the range of 0.03 to 10  ng/ml with an analytical sensitivity of 68  pg/ml. The sensor response shows high specificity and reproducibility. Hormone detection in clinical samples is further demonstrated and compared with a commercial enzyme-linked immunosorbent assay. The integrated device reported here has potential to detect other hormonal compounds or protein targets. Moreover, the presented concept enables the development of miniaturized, low-cost but highly sensitive optical microfluidic biosensors based on integrated polymer photodetectors with high potential for point-of-care diagnostics.

A mediator embedded micro-immunosensing unit for electrochemical detection on viruses within physiological saline media

To provide a time- and cost-saving alternative to the conventional methods for virus detection in biological media, this work presents an electrochemical micro-immunosensor based on the nickel hexacyanoferrate (NiHCF) redox mediator film coating the interdigitated microelectrodes (IDMEs). By chelation binding with no additional cross-linker, the 6xHis-tagged antibodies were immobilized on a NiHCF film. Secondly, an immunoassay response was enhanced by employing microbeads coated with 6xHis antibody. The electrochemical properties and the stability of the NiHCF film modified IDMEs were evaluated by cyclic voltammetry. The bead-induced impedance variations at the electrode film/electrolyte interface were characterized by electrochemical impedance spectroscopy and verified using FEM simulation. Experiments of virus detection were conducted through targeting the antigens of the vital infectious salmon viruses, such as infectious salmon anaemia virus, infectious pancreatic necrosis virus and salmonid alphavirus subtype 3. The micro-immunosensor exhibited detection limits as low as 10 pg ml−1 and detection sensitivities as high as 57.5 kΩ µM−1 within a physiological saline solution. Tests for multiple antigen–antibody interactions showed good detection specificity, as confirmed by ELISA. By incorporating the microfluidic network, electrochemical impedance micro-immunosensing units can be realized in a fully integrated platform for multiplex virus detection in tissue samples.

Wafer-Level Cu/Sn to Cu/Sn SLID-Bonded Interconnects With Increased Strength

Wafer level Cu-Sn solid liquid interdiffusion (SLID) bonding of interconnects was achieved by bonding two-layered Cu/Sn structures to each other. The bonded interconnects were investigated by mechanical, electrical and microscopic techniques. The Cu-Sn SLID interconnects were created by wafer-level bonding at 260°C. The bonded interconnects show shear strength of 45 MPa and a resistance of the order 100 mΩ . A major advantage of the Cu/Sn to Cu/Sn bonding scenario is to avoid the dynamic wetting of molten Sn to Cu, and simply replace with a liquid to liquid integration. Furthermore, the Sn overflow problem in a Cu/Sn SLID system was successfully addressed by designing a margin of 15 μm at the Cu pads to tolerate any Sn spreading. The uniformity requirement for electroplated Cu-Sn layers, which is crucial for achieving successful wafer-level bonding, is discussed. This wafer-level Cu-Sn SLID bonding process is a promising technique for 3-D assembly and packaging.

Intermetallic Compound Formation Mechanisms for Cu-Sn Solid–Liquid Interdiffusion Bonding

Cu-Sn solid–liquid interdiffusion (SLID) bonding is an evolving technique for wafer-level packaging which features robust, fine pitch and high temperature tolerance. The mechanisms of Cu-Sn SLID bonding for wafer-level bonding and three-dimensional (3-D) packaging applications have been studied by analyzing the microstructure evolution of Cu-Sn intermetallic compounds (IMCs) at elevated temperature up to 400°C. The bonding time required to achieve a single IMC phase (Cu3Sn) in the final interconnects was estimated according to the parabolic growth law with consideration of defect-induced deviation. The effect of predominantly Cu metal grain size on the Cu-Sn interdiffusion rate is discussed. The temperature versus time profile (ramp rate) is critical to control the morphology of scallops in the IMC. A low temperature ramp rate before reaching the bonding temperature is believed to be favorable in a SLID wafer-level bonding process.

Fluxless wafer-level Cu-Sn bonding for micro- and nanosystems packaging

For wafers with integrated and released sensitive micro- and nanosystems a fluxless wafer-level hermetic packaging solution is required. By using a 1.5 µm thick Sn layer as oxidation barrier for 5.0 µm thick Cu bond frames, the surface does not require pre-cleaning or use of any flux agent prior to, or during Cu-Sn bonding. With a tailored temperature and pressure bonding profile, the amount of Sn squeeze-out is reduced. Both for Cu-Sn bonds performed with new and aged electroplated films the measured shear strength is above 30 MPa. Further temperature cycling of bonded dies does not result in any reduction in bonding yield or shear strength.

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.

Spherical polymer particles in isotropic conductive adhesives a study on rheology and mechanical aspects

Isotropic conductive adhesive (ICA) filled with metal coated polymer spheres has been studied as a novel approach to increase the flexibility, and hence the reliability of the adhesive compared to traditional metal filled ICAs. In this paper, we have investigated the rheological properties of the novel ICA to evaluate its applicability in practical use. The current work also involves the investigation of the mechanical properties including shear strength of the novel ICA. Spherical polymer particles (SPP) of sizes Ø6 µm and Ø30 µm were investigated in the present study. The results show minor differences in the rheological properties and the adhesion strength for adhesives filled with particles in different sizes. Filling SPP into the adhesive matrix increases the viscosity of the system monotonically and continuously, in excellent accordance with model systems previously reported in the literature. Furthermore, the novel ICA exhibits high mechanical shear strength, being comparable to the traditional solder joint technology and twice higher than the traditional metal filled ICA.

Au-Sn fluxless SLID bonding: Effect of bonding temperature for stability at high temperature, above 400 °C

Fluxless SLID (Solid-Liquid InterDiffusion) bonding based on Au and Sn is presented, using two different processes, and bonding temperatures in the range 300–350 °C. The decomposition of the bond was tested by applying shear force while heating the samples. No bond delamination was observed for temperatures up to 350–400 °C, with 95 % of the tested samples surviving 400 °C without bond delamination. This is more than 100 °C higher than the melting temperature of the commonly used eutectic Au-Sn bond (80 wt% Au, melting at 278 °C). The Au-Sn system is particularly interesting since it is oxidation resistant, allowing fluxless bonding. With the SLID process, the metal system is applicable for true high-temperature applications.