Evanescent single-molecule biosensing with quantum limited precision

Sensors that are able to detect and track single unlabelled biomolecules are an important tool both to understand biomolecular dynamics and interactions at nanoscale, and for medical diagnostics operating at their ultimate detection limits. Recently, exceptional sensitivity has been achieved using the strongly enhanced evanescent fields provided by optical microcavities and nano-sized plasmonic resonators. However, at high field intensities photodamage to the biological specimen becomes increasingly problematic. Here, we introduce an optical nanofibre based evanescent biosensor that operates at the fundamental precision limit introduced by quantisation of light. This allows a four order-of-magnitude reduction in optical intensity whilst maintaining state-of-the-art sensitivity. It enable quantum noise limited tracking of single biomolecules as small as 3.5 nm, and surface-molecule interactions to be monitored over extended periods. By achieving quantum noise limited precision, our approach provides a pathway towards quantum-enhanced single-molecule biosensors.Comment: 17 pages, 4 figures, supplementary informatio

Silicon nanophotonic ring resonators sensors integrated in reaction tubes

Enzyme-linked immunosorbent assays (ELISA) are the most popular immunoassay techniques performed every day in hospitals and laboratories and they are used as a diagnostic tool in medicine and plant pathology, as well as a quality-control check in various industries. However, complex labeling techniques are required to be able to perform the assay and non-specific binding and endpoint timing are difficult to optimize. These issues could be solved by label-free techniques such as silicon nanophotonic microring resonator sensors, but this platform requires complex microfluidics, which is very much removed from the daily practice in e. g. hospital labs, which still relies to a large degree on platforms like 96-well microtiter plates or reaction tubes. To address these issues, here, we propose the combination of a simple and compatible reaction tube platform with label free silicon-on-insulator (SOI) photonic biosensors, where the flow is through the sensor chip as opposed to over the chip as in more conventional approaches. This device allows real time detection and analysis. Its great flexibility and small footprint make it ideal for an easy handling in any laboratory

Biosensors

A biosensor is defined as a detecting device that combines a transducer with a biologically sensitive and selective component. When a specific target molecule interacts with the biological component, a signal is produced, at transducer level, proportional to the concentration of the substance. Therefore biosensors can measure compounds present in the environment, chemical processes, food and human body at low cost if compared with traditional analytical techniques. This book covers a wide range of aspects and issues related to biosensor technology, bringing together researchers from 11 different countries. The book consists of 16 chapters written by 53 authors. The first four chapters describe several aspects of nanotechnology applied to biosensors. The subsequent section, including three chapters, is devoted to biosensor applications in the fields of drug discovery, diagnostics and bacteria detection. The principles behind optical biosensors and some of their application are discussed in chapters from 8 to 11. The last five chapters treat of microelectronics, interfacing circuits, signal transmission, biotelemetry and algorithms applied to biosensing

Conformational dynamics of a single protein monitored for 24 hours at video rate

We use plasmon rulers to follow the conformational dynamics of a single protein for up to 24 h at a video rate. The plasmon ruler consists of two gold nanospheres connected by a single protein linker. In our experiment, we follow the dynamics of the molecular chaperone heat shock protein 90, which is known to show open and closed conformations. Our measurements confirm the previously known conformational dynamics with transition times in the second to minute time scale and reveals new dynamics on the time scale of minutes to hours. Plasmon rulers thus extend the observation bandwidth 3/4 orders of magnitude with respect to single-molecule fluorescence resonance energy transfer and enable the study of molecular dynamics with unprecedented precision

Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

Evolvable Smartphone-Based Point-of-Care Systems For In-Vitro Diagnostics

Recent developments in the life-science -omics disciplines, together with advances in micro and nanoscale technologies offer unprecedented opportunities to tackle some of the major healthcare challenges of our time. Lab-on-Chip technologies coupled with smart-devices in particular, constitute key enablers for the decentralization of many in-vitro medical diagnostics applications to the point-of-care, supporting the advent of a preventive and personalized medicine. Although the technical feasibility and the potential of Lab-on-Chip/smart-device systems is repeatedly demonstrated, direct-to-consumer applications remain scarce. This thesis addresses this limitation. System evolvability is a key enabler to the adoption and long-lasting success of next generation point-of-care systems by favoring the integration of new technologies, streamlining the reengineering efforts for system upgrades and limiting the risk of premature system obsolescence. Among possible implementation strategies, platform-based design stands as a particularly suitable entry point. One necessary condition, is for change-absorbing and change-enabling mechanisms to be incorporated in the platform architecture at initial design-time. Important considerations arise as to where in Lab-on-Chip/smart-device platforms can these mechanisms be integrated, and how to implement them. Our investigation revolves around the silicon-nanowire biological field effect transistor, a promising biosensing technology for the detection of biological analytes at ultra low concentrations. We discuss extensively the sensitivity and instrumentation requirements set by the technology before we present the design and implementation of an evolvable smartphone-based platform capable of interfacing lab-on-chips embedding such sensors. We elaborate on the implementation of various architectural patterns throughout the platform and present how these facilitated the evolution of the system towards one accommodating for electrochemical sensing. Model-based development was undertaken throughout the engineering process. A formal SysML system model fed our evolvability assessment process. We introduce, in particular, a model-based methodology enabling the evaluation of modular scalability: the ability of a system to scale the current value of one of its specification by successively reengineering targeted system modules. The research work presented in this thesis provides a roadmap for the development of evolvable point-of-care systems, including those targeting direct-to-consumer applications. It extends from the early identification of anticipated change, to the assessment of the ability of a system to accommodate for these changes. Our research should thus interest industrials eager not only to disrupt, but also to last in a shifting socio-technical paradigm