Opening windows on new biology and disease mechanisms: development of real-time in vivo sensors

From X-ray radiology to blood panels, medicine is informed by the status of in vivo systems and their deviations from normal ranges. It is now widely acknowledged that the fundamental aetiology of many disease states can be understood at the molecular level. Over the past half a century there has been a push towards the development of novel technologies to probe the in vivo molecular status of biological systems for diagnosis, prognosis and response to therapies [1]. This Theme Issue will highlight some of the most recent exciting work in the fields of molecular-, nano-, and micro-scale devices for real-time in vivo sensing. Although this field is already large and growing, this Introduction will attempt to provide context and background for understanding this set of papers, and how they attempt to address the unique challenges that arise in the development of these novel and powerful devices. At the most fundamental level, a sensor is simply a device capable of quantifying or detecting a specific, biologically relevant analyte. Practically, this consists of a detector (such as an electrode, antibody, aptamer, peptide or enzyme) paired with a detection method (which may be optical, electrochemical or magnetic, among others). In this Theme Issue, we will focus on biosensors capable of interrogating the status of biological systems in vivo and at high temporal resolution. These in vivo sensors promise to have great utility in the future, as they will allow continuous, rapid monitoring of biological systems in the context of disease, response to therapy, cell–drug interactions or understanding normal biology. The first real-time in vivo sensors were electrochemical glucose detectors that took advantage of the catalytic activity of glucose oxidase to reliably and simply detect glucose levels over time [2]. These electrochemical detection modalities have since been improved upon and incorporated into devices capable of detecting numerous analytes, including xanthine and lactate [3]. Optical sensors have recently become increasingly popular owing to their high potential for multiplexing and ease of adaptation from existing in vitro assays. For high spatial resolution, these detectors require complex imaging modalities, such as two-photon confocal imaging, for reliable temporal and spatial resolution. Feasible use of such sensors in human patients will probably sacrifice spatial resolution for broad in vivo accuracy, as in embedded optical glucose sensors [4]. Positron emission tomography sensors are well established, with a growing list of increasingly validated substrates for in vivo sensing including glucose metabolism, oxygenation, neurotransmitters and proteases. Detection methods commonly used with in vitro sensors, such asthose that take advantage of surface plasmon resonance or the piezoelectric effect have not yet found wide utility with in vivo sensors. Adaptation of these techniques for in vivo sensing will surely expand the breadth of in vivo sensors in the future. Yasun et al. [5] specifically review recent advances in the field of gold nanorods with exciting potential for in vivo applications, including the development of photoacoustic imaging techniques for cancer. Although the range of in vitro biosensors is enormous, encompassing a huge variety of detection modalities with exquisite sensitivity, the range of in vivo