Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications

Fully integrated digital microfluidics platform for automated immunoassay; a versatile tool for rapid, specific detection of a wide range of pathogens

© 2018 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.With the tangible threat posed by the release of chemical and biological warfare (CBW) agents, detection of airborne pathogens is a critical military and security concern. Recent air sampling techniques developed for biocollection take advantage of Electrowetting on Dielectric (EWOD) to recover material, producing highly concentrated droplet samples. Bespoke EWOD-based digital microfluidics platforms are very well suited to take full advantage of the microlitre concentrated droplet resulting from this recovery process. In this paper we present a free-standing, fully automated DMF platform for immunoassay. Using this system, we demonstrate the automated detection of four classes of CBW agent simulant biomolecules and organisms each representing credible threat agents. Taking advantage of the full magnetic separation process with antibody-bound microbeads, rapid and complete separation of specific target antigen can be achieved with minimal washing steps allowing for very rapid detection. Here, we report clear detection of four categories of antigens achieved with assay completion times of between six and ten minutes. Detection of HSA, Bacillus atrophaeus (BG spores), MS2 bacteriophage and Escherichia coli are demonstrated with estimated limit of detection of respectively 30 ng ml -1, 4 × 10 4 cfu ml -1, 10 6 pfu ml -1 and 2 × 10 7 cfu ml -1. The fully-integrated portable platform described in this paper is highly compatible with the next generation of electrowetting-coupled air samplers and thus shows strong potential toward future in-field deployable biodetection systems and could have key implication in life-changing sectors such as healthcare, environment or food security.Peer reviewe

Device modelling for bendable piezoelectric FET-based touch sensing system

Flexible electronics is rapidly evolving towards devices and circuits to enable numerous new applications. The high-performance, in terms of response speed, uniformity and reliability, remains a sticking point. The potential solutions for high-performance related challenges bring us back to the timetested silicon based electronics. However, the changes in the response of silicon based devices due to bending related stresses is a concern, especially because there are no suitable models to predict this behavior. This also makes the circuit design a difficult task. This paper reports advances in this direction, through our research on bendable Piezoelectric Oxide Semiconductor Field Effect Transistor (POSFET) based touch sensors. The analytical model of POSFET, complimented with Verilog-A model, is presented to describe the device behavior under normal force in planar and stressed conditions. Further, dynamic readout circuit compensation of POSFET devices have been analyzed and compared with similar arrangement to reduce the piezoresistive effect under tensile and compressive stresses. This approach introduces a first step towards the systematic modeling of stress induced changes in device response. This systematic study will help realize high-performance bendable microsystems with integrated sensors and readout circuitry on ultra-thin chips (UTCs) needed in various applications, in particular, the electronic skin (e-skin)

Electrowetting-Based Digital Microfluidics Platform for Automated Enzyme-linked Immunosorbent Assay

Electrowetting is the effect by which the contact angle of a droplet exposed to a surface charge is modified. Electrowetting-on-dielectric (EWOD) exploits the dielectric properties of thin insulator films to enhance the charge density and hence boost the electrowetting effect. The presence of charges results in an electrically induced spreading of the droplet which permits purposeful manipulation across a hydrophobic surface. Here, we demonstrate EWOD-based protocol for sample processing and detection of four categories of antigens, using an automated surface actuation platform, via two variations of an Enzyme-Linked Immunosorbent Assay (ELISA) methods. The ELISA is performed on magnetic beads with immobilized primary antibodies which can be selected to target a specific antigen. An antibody conjugated to HRP binds to the antigen and is mixed with H 2O 2/Luminol for quantification of the captured pathogens. Assay completion times of between 6 and 10 min were achieved, whilst minuscule volumes of reagents were utilized.Peer reviewe

Miniaturization of fluorescence sensing in optofluidic devices

International audienceSuccessful development of a micro-total-analysis system (μTAS, lab-on-a-chip) is strictly related to the degree of miniaturization, integration, autonomy, sensitivity, selectivity, and repeatability of its detector. Fluorescence sensing is an optical detection method used for a large variety of biological and chemical assays, and its full integration within lab-on-a-chip devices remains a challenge. Important achievements were reported during the last few years, including improvements of previously reported methodologies, as well as new integration strategies. However, a universal paradigm remains elusive. This review considers achievements in the field of fluorescence sensing miniaturization, starting from off-chip approaches, representing miniaturized versions of their lab counter-parts, continuing gradually with strategies that aim to fully integrate fluorescence detection on-chip, and reporting the results around integration strategies based on optical-fiber-based designs,optical layer integrated designs, CMOS-based fluorescence sensing, and organic electronics. Further successful development in this field would enable the implementation of sensing networks in specific environments that, when coupled to Internet of-Things (IoT) and artificial intelligence (AI), could provide real-time data collection and, therefore, revolutionize fields like health, environmental, and industrial sensing

Integration of GMR sensors with different technologies

Less than thirty years after the giant magnetoresistance (GMR) effect was described, GMR sensors are the preferred choice in many applications demanding the measurement of low magnetic fields in small volumes. This rapid deployment from theoretical basis to market and state-of-the-art applications can be explained by the combination of excellent inherent properties with the feasibility of fabrication, allowing the real integration with many other standard technologies. In this paper, we present a review focusing on how this capability of integration has allowed the improvement of the inherent capabilities and, therefore, the range of application of GMR sensors. After briefly describing the phenomenological basis, we deal on the benefits of low temperature deposition techniques regarding the integration of GMR sensors with flexible (plastic) substrates and pre-processed CMOS chips. In this way, the limit of detection can be improved by means of bettering the sensitivity or reducing the noise. We also report on novel fields of application of GMR sensors by the recapitulation of a number of cases of success of their integration with different heterogeneous complementary elements. We finally describe three fully functional systems, two of them in the bio-technology world, as the proof of how the integrability has been instrumental in the meteoric development of GMR sensors and their applications.Peer ReviewedPostprint (published version

Transfer-print integration of GaAs p-i-n photodiodes onto silicon nitride waveguides for near-infrared applications

We demonstrate waveguide-detector coupling through the integration of GaAs p-i-n photodiodes (PDs) on top of silicon nitride grating couplers (GCs) by means of transfer-printing. Both single device and arrayed printing is demonstrated. The photodiodes exhibit dark currents below 20 pA and waveguide-referred responsivities of up to 0.30 A/W at 2V reverse bias, corresponding to an external quantum efficiency of 47% at 860 nm. We have integrated the detectors on top of a 10-channel on-chip arrayed waveguide grating (AWG) spectrometer, made in the commercially available imec BioPIX-300 nm platform. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen