Metal-Alloy Cu Surface Passivation Leads to High Quality Fine-Pitch Bump-Less Cu-Cu Bonding for 3D IC and Heterogeneous Integration Applications

In this paper, we report a low temperature, fine-pitch, bump-less, damascene compatible Cu-Cu thermocompression bonding, using an optimized ultra-thin passivation layer, Constantan, which is an alloy (Copper-Nickel) of 55% Cu and 45% Ni. Surface oxidation and its roughness are the major bottlenecks in achieving high quality, low temperature, and fine-pitch Cu-Cu bonding. In this endeavor, we have used Cu rich alloy (Constantan) for passivation of Cu surface prior to bonding. We have systematically optimized the constantan passivation layer thickness for high quality low temperature, low pressure, bump-less Cu-Cu bonding. Also, we have studied systematically the efficacy of Cu surface passivation with optimized ultra-thin constantan alloy passivation layer. After rigorous trial and optimization, we successfully identified 2 nm passivation layer thickness, at which very high quality Cu-Cu bonding could be accomplished at sub 200 °C with a nominal contact pressure of 0.4 MPa. Post-bonding, electrical and mechanical characterization were validated using four-probe IV measurement and bond strength measurement respectively. Furthermore, Cu-Cu bonding interface was analyzed using IR wafer bonder inspection tool. Very high bond strength of 163 MPa and defect free interface observed by WBI-IR clearly suggests, Cu-Cu finepitch bonding with optimized ultra-thin alloy of 2 nm thick constantan, is of very high quality and reliable. Moreover, this novel bonding approach with alloy based interconnect passivation technique is the prime contestant for future heterogeneous integration

Real-time smart multisensing wearable platform for monitoring sweat biomarkers during exercise

Sweat secreted by the human eccrine sweat glands can provide valuable biomarker information during exercise in hot and humid conditions. Real-time noninvasive biomarker recordings are therefore useful for evaluating the physiological conditions of an athlete such as their hydration status during endurance exercise. In this work, we describe a platform that in- cludes different sweat biomonitoring prototypes of cost-effective, smart wearable devices for continuous biomonitoring of sweat during exercise. One prototype is based on conformable and disposable soft sensing patches with an integrated multi-sensor array requiring the integration of different sensors and printed sensors with their corresponding functionalization protocols on the same substrate. The second is based on silicon based sensors and paper microfluidics. Both platforms integrate a multi-sensor array for measuring sodium, potassium, and pH in sweat. We show preliminary results obtained from the multi-sensor prototypes placed on two athletes during exercise. We also show that the machine learning algorithms can predict the percentage of body weight loss during exercise from biomarkers such as heart rate and sweat sodium concentration collected over multiple subjects

Multisensing wearables for real-time monitoring of sweat electrolyte biomarkers during exercise and analysis on their correlation with core body temperature

Sweat secreted by the human eccrine sweat glands can provide valuable biomarker information during exercise. Real-time non-invasive biomarker recordings are therefore useful for evaluating the physiological conditions of an athlete such as their hydration status during endurance exercise. This work describes a wearable sweat biomonitoring patch incorporating printed electrochemical sensors into a plastic microfluidic sweat collector and data analysis that shows the real-time recorded sweat biomarkers can be used to predict a physiological biomarker. The system was placed on subjects carrying out an hour-long exercise session and results were compared to a wearable system using potentiometric robust silicon-based sensors and to commercially available HORIBA-LAQUAtwin devices. Both prototypes were applied to the real-time monitoring of sweat during cycling sessions and showed stable readings for around an hour. Analysis of the sweat biomarkers collected from the printed patch prototype shows that their real-time measurements correlate well (correlation coefficient ≥0.65 ) with other physiological biomarkers such as heart rate and regional sweat rate collected in the same session. We show for the first time, that the real-time sweat sodium and potassium concentration biomarker measurements from the printed sensors can be used to predict the core body temperature with root mean square error (RMSE) of 0.02 °C which is 71% lower compared to the use of only the physiological biomarkers. These results show that these wearable patch technologies are promising for real-time portable sweat monitoring analytical platforms, especially for athletes performing endurance exercise

Real-Time Multi-Ion Detection in the Sweat Concentration Range Enabled by Flexible, Printed, and Microfluidics-Integrated Organic Transistor Arrays

Organic electrochemical transistors (OECTs) show remarkable promise as biosensors, thanks to their high signal amplification, simple architecture, and the intrinsic flexibility of the organic material. Despite these properties, their use for real-time sensing in complex biological fluids, such as human sweat, is strongly limited due to the lack of cross-sensitivity and selectivity studies and the use of rigid and bulky device configurations. Here, the development of a novel flexible microfluidics-integrated platform with an array of printed ion-selective OECTs enables multi-ion detection in a wearable fashion. This is achieved by coating the poly(3,4-ethylene dioxythiophene):polystyrene sulfonate (PEDOT:PSS) channels of the transistors with three different ion-selective membranes (ISMs). Systematic electrical and sensing analysis of the OECTs with ISMs show a minimal impact of the membranes on the electrical and time responses of the transistors while providing high ion selectivity. This work combines for the first time real-time and selective multi-ion detection with an array of inkjet-printed and flexible organic transistors coated with different ISMs, demonstrating state-of-the-art sensing capabilities of approximate to 10 mu A dec(-1)for potassium, sodium, and pH. This flexible OECTs sensing platform paves the way to the next generation devices for continuous electrolytes monitoring in body fluids

Thin film organic electrochemical transistors based on hybrid PANI/PEDOT:PSS active layers for enhanced pH sensing

We report on organic electrochemical transistors (OECTs) with active channels made of hybrid inkjet-printed poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and electropolymerized polyaniline (PANI) layers, exhibiting simultaneously improved electrical and pH sensing characteristics. The aniline electropolymerization with an optimum 6-cycles of cyclic voltammetry forms a porous PANI microstructured layer on the PEDOT:PSS film, resulting in high signal linearity and sensitivity of about 100 mV/pH and 20 μA/pH. The electrochemical impedance spectroscopy analysis demonstrates a 9X higher-change of interfacial capacitance when decreasing the pH with the hybrid PANI-PEDOT:PSS layer, in comparison to a bare PEDOT:PSS layer. The simple fabrication process and the high signal amplification pave the way for flexible and higher-performance pH-sensitive OECTs. These scalable devices, combined with ion-selective OECTs, would lead to a novel tool for multi-parametric analysis in different biofluids

Printed Iontophoretic‐Integrated Wearable Microfluidic Sweat‐Sensing Patch for On‐Demand Point‐Of‐Care Sweat Analysis

In recent years, wearable epidermal sweat sensors have received extensive attention owing to their great potential to provide personalized information on the health status of individuals at the molecular level. For on‐demand medical analysis of sweat in sedentary conditions, a cost‐effective wearable integrated platform combining sweat stimulation, sampling, transport, and analysis is highly desirable. In this work, a printed iontophoretic system integrated into a microfluidic sensing platform, which combines sweat induction, collection, and real‐time analysis of sweat‐ions into a single patch for on‐demand sweat monitoring on human subjects in stationary conditions is reported. The incorporation of microfluidics features facilitates sweat sampling, collection, and guiding through capillary effect. The multisensing sensor array exhibits sensitivity close to Nernstian behavior for sodium, potassium, and pH. The correlation between the concentrations of ions measured with the sweat patch and with ion chromatography analysis demonstrates the applicability of the system for real‐time point‐of‐care monitoring of the health status of individuals. Furthermore, the sweat patch electronic interface with wireless transmission enables real‐time data monitoring and storage over a cloud platform. This printed iontophoretic‐integrated fluidic sweat patch provides a cost‐effective solution for the on‐demand analysis of sweat components for healthcare applications

Highly-sensitive Label-free Differential Pulse Voltammetric Immunosensor for Diagnosis of Infectious Diseases Based on Electrospun Copper Doped ZnO Nanofiber Biosensing Platform

Rapid detection of infectious diseases has generated significant interest in recent years. The time consuming and costly conventional diagnostics methods substantiate the need to develop a cost-effective rapid infectious disease detection platform to address the persistently threatening health issues in developing countries. The recent advancements in nanotechnology and biosensing have manifested the potential to deliver an effective point-of-care diagnostics platform. In this work, the synthesis and fabrication of an ultrasensitive Copper doped Zinc oxide nanofiber based biosensing platform is reported. Copper doped Zinc oxide nanofibers are synthesized by simple electrospinning technique with fiber diameter of 100-200 nm. The structural and morphological characteristics of the nanofibres are studied using X-ray diffraction and field emission scanning electron microscopy. The label free detection of HRP2 protein with the Copper doped Zinc Oxide nanofiber has been investigated by Differential pulse voltammetric technique. Mercaptopropionic acid treatment of Copper doped Zinc oxide nanofiber generates carboxylic acid groups, which facilitate the covalent conjugation of Anti-HRP2. To the best of our knowledge, the fabricated immunosensor displays better sensitivity than the best malaria sensor reported in the literature based on different nanomaterials and different detection mechanism. The proposed platform exhibits very low limit of detection of 10 attogram per ml for the targeted HRP2 protein in a wide detection test range (ag/ml -μg/ml). The novel biosensor platform demonstrates good stability and selectivity which can be implemented for point-of-care diagnosis of biomarkers related to other infectious diseases

Nonlithographic Fabrication of Plastic-Based Nanofibers Integrated Microfluidic Biochip for Sensitive Detection of Infectious Biomarker

We report fabrication of a fully integrated plastic based microfluidic biochip for biosensing application. The microfluidic channels were fabricated by tune transfer method and integrated with the prefunctionalized sensing platform. This approach to assembling microchannels into prefunctionalized sensing substrate facilitates controlled functionalization and prevents damages on the functionalized surface. The sensing platform comprised a three-electrode system, in which the sensing electrode was integrated with antibody immobilized carbon nanotubes-zinc oxide (C-ZnO) nanofibers. Electrospinning technique was used to synthesize C-ZnO nanofibers and the surface of the nanofibers was covalently conjugated with histidine rich protein II antibodies (AntiHRP II) toward detection of infectious malarial specific antigen, namely histidine-rich protein II (HRP II). The analytical performance of the fabricated biochip was evaluated by differential pulse voltammetry method. The device exhibited a high sensitivity of 1.19 mA/((g mL^–1)/cm²) over a wide detection range (10 fg/mL to 100 μg/mL) with a low detection limit of 7.5 fg/mL toward HRP II detection. This fully integrated biochip offers a promising cost-effective approach for detection of several other infectious disease biomarkers