Nanobiosensors have been successful for in vitro as well as in vivo detection of several biomolecules and it is expected that this technology will revolutionize point-of-care and personalized diagnostics, and will be extremely applicable for early disease detection and therapeutic applications. This book describes the emerging nanobiosensor technologies which are geared towards onsite clinical applications and those which can be used as a personalised diagnostic device. Biosensor technologies and materials covered include electrochemical biosensors; implantable microbiosensors; microfluidic technology; surface plasmon resonance-based technologies; optical and fibre-optic sensors; lateral flow biosensors; lab on a chip; nanomaterials based (graphene, nanoparticles, nanocomposites, and other carbon nanomaterial) sensors; metallic nanobiosensors; wearable and doppler-based non-contact vital signs biosensors; and technologies for smartphone based disease diagnosis. Clinical applications of these technologies covered in this book include detection of various protein biomarkers, small molecules, cancer and bacterial cells; detection of foodborne pathogens; generation and optimisation of antibodies for biosensor applications; microRNAs and their applications in diagnosis for osteoarthritis; detection of circulating tumor cells; online heartbeat monitoring; analysis of drugs in body fluids; sensing of nucleic acids; and monitoring oxidative stress.
Inspec keywords: microorganisms; nanosensors; health care; bioMEMS; patient diagnosis; patient monitoring; nanocomposites; electrochemical sensors; cancer; lab-on-a-chip; tumours; nanoparticles; microfluidics; telemedicine; cellular biophysics; proteins; nanomedicine; microsensors; molecular biophysics; bioelectric potentials; graphene; surface plasmon resonance; smart phones; body sensor networks; biosensors; fibre optic sensors; RNA
Other keywords: osteoarthritis diagnosis; lateral flow biosensors; C; surface plasmon resonance-based technologies; body fluids; lab-on-a-chip; drug analysis; wearable-based noncontact vital signs biosensors; onsite biomedical diagnosis; protein biomarker detection; electrochemical biosensors; personalised diagnostic device; microfluidic technology; bacterial cell detection; online heartbeat monitoring; nanoparticles; oxidative stress monitonng; doppler-based noncontact vital signs biosensors; circulating tumor cell detection; nanobiosensor technologies; carbon nanomaterial; smartphone based disease diagnosis; fibre-optic sensors; graphene; nanocomposites; implantable microbiosensors; foodbome pathogen detection; microRNA; cancer detection; nucleic acid sensing
Subjects: Wireless sensor networks; Biosensors; Microfluidics and nanofluidics; Molecular biophysics; Microsensors and nanosensors; Mobile radio systems; Electrical activity in neurophysiological processes; Biomedical measurement and imaging; Cellular biophysics; Nanotechnology applications in biomedicine; Applied fluid mechanics; Chemical sensors; Biomedical communication; Biosensors; Patient diagnostic methods and instrumentation; Micromechanical and nanomechanical devices and systems; MEMS and NEMS device technology; Chemical sensors; Electrochemical analytical methods
Due to the unique properties in terms of excellent conductivity, high surface area-to-volume ratio, abundant surface chemical properties, and superior electrocatalytic activity, AuNPs are considered to be promising nanomaterial for diagnostic purpose and biomedical applications. A large number of electrochemical biosensors based on AuNPs have been developed to detect various disease-related analytes like small molecules, DNA, proteins, and cells. The efficient functions of AuNPs in the biosensors are summarized in three aspects: (i) improvement of electron transfer efficiency, (ii) immobilization of biological recognition element, and (iii) signal generation and amplification. As a nanomaterial allowing abundant modification, AuNPs enable various novel and facile designs for electrochemical biosensors with high sensitivity and reliability. In particularly, the nanocomposites composed of AuNPs and other materials provide the biosensor with multiple functional platforms. The combination of AuNPs with DNA amplification techniques offers possibility of cascade signal amplification.
This review focuses on the advances in development of in-vivo microbiosensors in last five years. Many of the in-vivo microsensors that sometimes are loosely termed “biosensors,”but that don't contain biological recognition elements. For example, in-vivo real-time detection of nitric oxide, non-enzymatic electrochemical sensors using direct oxidation of glucose on the electrode surface that don't have biological recognition elements (such as enzymes, proteins, oligonucleotides),or boronic acid derivatives based fluorescence glucose sensors fall outside this survey.
Pathogen detection is of utmost importance because of health and safety concern. The main disadvantages of conventional pathogen detection methods are the multistep procedure and long-time requirements. A rapid, portable and accurate diagnostic technique can be provided by a biosensor and thus prevention from the outbreak of any epidemic.Sexually transmitted diseases (STDs) are a public health problem, and their prevalence is rising even in developed nations, in the era of HIV/AIDS. A sequencespecific electrochemical STD sensor based on self-assembled monolayer specific to detection of Gonorrhoea, an STD, has been fabricated by Singh et al. An electrochemical biosensor for the detection of short DNA sequences related to the human immunodeficiency virus type 1 (HIV-1) has been developed by Wang etal.
In this work, the authors discuss the utilization of microchip-based separation systems for chemically and biologically valuable analytes. We have described the details of many substantial articles explaining the design of microchips, and utilities for their preparation, so that readers might understand the principles behind such devices and relevant detection strategies. The current challenges and future outlook have been discussed in detail in order to provide a clear understanding about the fundamentals of sensor design and performance that have the real possibility of upgrading the field. We have categorized this work into many sections based on their applications for the convenience.
This chapter describes some representative examples of in vitro detection of cancer and bacterial cells within the scope of biosensor systems. In cancer cell detection, priority is given to aptamers-based biosensors and the detailed information about the detection of cancer cells with the help of aptamers is explained. In the case of bacterial cells detection, electrochemical and optical biosensors that produce an electronic or optical signal proportional to the specific interaction between the target and the recognition molecule immobilized on the biosensor is elaborately exampled. In addition, microfluidics, LOC and paper-based detection systems for in vitro bacterial cells detection are emphasized in the chapter.
With the above-mentioned set-ups, biaocre-based SPR technology has several appealing advantages which include reproducible results, stable baselines, low nonspecific binding, high chemical stability, high sensitivity, regeneration and re-use, fast and convenient capture of biomolecules, surface stability in several conditions, series of binding steps can be performed compared with other analytical techniques, automatic sample handling, programmable for experimental performance without users' present, choice of ligand, label-free detection and real-time analysis. With these applications, biacore served for scientific community about two decades with several products by drastic improvements and expect for more advanced systems from to obtain comprehensive information.
The miniaturisation of biosensors - microbiosensors has definite advantages over conventional biosensors, various microbiosensors could be integrated to construct multifunctional microbiosensor assays. For continuous real time in vivo measurements, other than small size, the microbiosensors should be useful for easy placement within a blood vessel (i.e. artery for blood gases/pH; vein for glucose/lactate) or under the skin in subcutaneous space (mainly for glucose) and exhibit long-term stability. Enzyme-based amperometric microbiosensors are presently the dominant biosensors for monitoring and detection of biomolecules and have already shown great potentials to be translated into implantable for diseases like diabetes. The synergy between implantable biosensors and nanotechnology is crucial in the areas of miniaturisation and post-implantation inflammation. Since the degree of inflammation is largely dependent on the size of the implanted device, nanotechnology has been used to decrease not only the inflammation but also the size of the implants. Development of this implantable biosensor would require a multidisciplinary team. Indeed, the future development of implantable microbiosensors and devices will require the combination of multidisciplinary areas like chemistry, solid state physics, bioengineering and medicine.
Recent developments of nanomaterials based biosensors for clinical diagnosis by detecting several pathogens as infectious diseases management at an early stage is currently of prime interest so as to circumvent the delay in diagnosis. The incorporation of nanomaterial transducer with collaborative transducing elements opens up a new era for further development of novel biosensors for detecting a broad range of target analytes. Hence, the advantages of nanomaterials based biosensors over existing detection methodologies and the role of various immobilization matrices used for fabrication of nanomaterials based biosensors are discussed. The conventional pathogen detection methods are sensitive but still lag behind the analytical methods due to long response time and decreasing in the response time is a needle in a haystack problem. Besides this, efforts have been made to discuss the various techniques used for biosensor construction, the analytical performance of these biodevices for bacterial and viral pathogens for their applications to medical diagnosis. Recent developments in the buzzword `nanotechnology' and material science can be advantageously used to obtain engineered and customerized nanomaterials that could provide novel platforms for immobilization of biorecognition component that may lead to the development of useful and reliable biosensor devices. And the use of microarray for simultaneous measurement with integrated microfluidic system may provide solution for the fabrication of smart low cost point-of-care devices in reliable pathogen detection. Efforts should be directed towards the synthesis of novel nanomaterials for the fabrication of electrochemical, optical and other biosensors on a large scale so as to benefit the mankind. With exposure of the commercial market the applications of the biosensor technology can be greatly enhanced and with time, miniaturized biosensor for pathogen detection may become available that could be used near a patient's bedside, a doctor's clinic or even home use.
Here, we briefly discuss the past, present, and possible future of label-free optical biosensors in cell research, especially focusing on the kinetic monitoring of cellular adhesion. Currently available optical biosensors possess outstanding potentials still not rightfully recognized and still waiting to be fully exploited in the field of cell science. Thus, during the description we give special emphasis to the advantages that the state-of-the-art optical cell-based biosensors possess as compared to microscopeor force measurement-based techniques widely used to characterize cell adhesion. To name here only a few, they enable label-free detection close to a planar sensor surface, have high sensitivity, and generate superior quality kinetic data. Such information-rich kinetic data, in turn, can be analyzed in-depth and comparatively. To exemplify the importance of in-depth kinetic analysis, we review a recent study, in which the Epic BenchTop high-throughput optical biosensor was used to measure the dependence of cancer cell adhesion kinetics on the surface density of integrin ligands. Based on the kinetic data, a model enabling the label-free determination of the dissociation constant of the adhesion ligands bound to their native cell membrane receptors has been constructed. As an outlook, the perspectives of the technology is briefly discussed.
SERS combines high sensitivity and selectivity with practicality through the use of microfluidics. SERS based techniques are cost effective and rapid which makes them an ideal biosensor for the detection of pathogens.
Antibodies are ideal recognition elements for use in many biosensor-based applications. The approaches used with all antibody types are described. In addition, using molecular biology-based techniques antibodies may be generated and altered, thereby maximising specificity, sensitivity, stability, orientation and other factors to achieve optimal overall performance in many applications.
The SP-based devices with associated smart applications are being used for personalized general healthcare monitoring, notably analyses of blood glucose, weight, heart rate, etc., a major driving force in the creation of new enterprises such as iHealth LLC, Runtastic, AliveCor, GENTAG and Holomic LLC. The success of SP-based devices and smart applications together with improved diagnostic procedures will warrant further developments and applications of commercially-viable SP-IVD tools in the coming years.
A typical lateral flow biosensor employs a sandwich detection system and uses tracer(s) to generate detectable signal(s) (Figure 13.1). However, recent advances in nanomaterials offer a wide variety of improvement options, including new detection methodologies, signal transformation and improvements in sensitivity and specificity [4-6]. In this chapter, we describe the basic lateral flow detection system, the major components and their functions, critical parameters for successful lateral flow detection, and applications in biosensing. We also point out the hurdles facing commercial development of lateral flow biosensors. In particular, we consider future perspectives of lateral flow biosensors for personalized onsite biomedical diagnosis.
Numerous studies show that miRNAs are involved in some significant cellular processes like apoptosis, differentiation, organ development, and expected to be diagnostic and prognostic biomarkers of cacoethic tumors. Also, miRNA expression was detected both in plasma and synovial fluid from OA patients. A large number of studies show that miRNA plays an important role in regulating the gene expression in OA which is characterized by the progressive destruction of articular cartilage. Therefore, understanding the role of miRNA in OA promises to provide a breakthrough in OA detection and treatment.
The author shows that it is possible to classify electrochemical capacitive biosensor devices based on non-faradaic and faradaic processes. Potentiometric, amperometric and impedimetric biosensors are discussed, both in connection with their operating principles and their potential applications. In general, it can be observed that capacitive biosensors are still at an early stage of development. The applicability of these kinds of devices is mainly focused in immune sensing aiming, for instance, at the development of sensing devices for early diagnostic applications. Other possibilities such as applications focused on virus and air chemical contaminants detection are also potential applications to be explored. The main disadvantage of capacitive devices is the need for a very controllable molecular structure on the surface of the device, achieved by control of metallic depositions or by mechanical/electrochemical combined polishing. The advantages compared with other electrochemical biosensor devices lay in the point-of-care and bedside applications, as there is no need for an additional redox probe on the complex biological sample of patients. Also, these devices show promising multiplexing and miniaturization capabilities. In the future there are potentially many assay applications building on electrochemical capacitive concepts as useful electro-analytical transducer signals of sensing interfaces and devices.
This chapter demonstrates how AC electrokinetics capacitive sensing method is implemented to monitor protein-protein interactions, as well as to detect various bioparticle binding to an electrode. It is shown as a rapid, sensitive, quantitative and highly accessible approach to various affinity sensing needs. The development and optimization of the assay is also given with respect to AC signal and electrode dimensions.
To be successful, all fibre optical biosensor based devices must possess the following characteristics: low detection limits, low cost, simplicity of design and operation, reliability, accuracy, ruggedness, low detection time of analyte, ease of calibration and some degree of reversibility. These devices should be capable of continuous flow measurements, minimal operator attendance and the determination of multiple analytes. Fibre optical biosensors should offer new capabilities or significant improvements over existing methods to be successful in an increasingly competitive marketplace. Some of the obstacles common to all field analytical methods include the diversity of compounds and the complexity of matrices in samples, the variability in data quality requirements and the broad range of possible monitoring applications.
With the development of nanotechnology and nanobiomedicine, it is well known that cells could sense and respond to the nanotopography of material. The importance of nanomaterials has been constantly tested with the exploration of the interaction between cells and the nanotopography of material. In the last decade, the nanostructured materials have been incorporated with CTC detecting devices, and the design of nanomaterials becomes the key to overcome current limitations associated with CTC capture and analysis. As there have been some pretty good reviews on nanostructured substrates for guiding cell behaviors [14] or CTC isolation [15, 16], here we will focus on the progress of the design of nanostructured interfaces for CTC biosensors in the past decades, and highlight the new explorations on isolation concepts based on nanostructured interfaces, in an attempt, to achieve available CTCs for accurate downstream detection and analysis.
Different types of cardiac bio-sensors have evolved over the past few decades, depending upon the type of cardiac signals used to estimate the heart-rate. Wearable cardiac biosensors use ECG as the input for heart-rate detection, whereas Implantable Cardioverter Defibrillator (ICD) uses EGM to monitor heart-rate as well as to provide necessary defibrillation to maintain proper heart rhythm. However, a Doppler-based non-contact vital signs sensor monitors the physiologically modulated cardio-pulmonary movement signal to detect the heart rate; more detailed physics of which will be discussed later in this chapter. Next, we will introduce and describe the wearable ECG sensors first, as they are getting smaller and cheaper and more popular on the market today.
In this chapter, we will first discuss some basics about POCT, then lab-onchip systems for POCT will be presented, including materials and fabrication, detection and applications to drug analysis in body fluids.
Hydrogels are three dimensional polymeric networks which are able to absorb aqueous solution. The hydrated environment within the hydrogels permits the immobilized biomolecules to retain their structure and activity. Due to their favorable mass transfer and interfacial properties, immobilized or entrapped biomolecules remain accessible and can interact with the analytes. In addition, the hydrogel-based biosensors also leverage the hydrogel specific properties including swelling, phase transitions, and optical transparency to enhance the signal/noise ratio for sensing. Furthermore, by virtue of good biocompatibility and ability to protect the biorecognition elements from bio-fouling, the hydrogel matrices also improve the sensitivity of the implantable biosensors.
Nanoscale structures like graphene nanowires, nanotubes, nanowalls and nanorods offer many unique features and show great promise for faster response and higher sensitivity at the device interface. Their nanometer dimensions show an increased sensing surface to volume and strong binding properties, thus allowing a higher sensitivity. Because of the graphene interesting advantages among other nanomaterials, this chapter is devoted to the increasing applications of this material for the fabrication of highly sensitive and selective electrochemical biosensors. This chapter will focus only on applications of this nanomaterial as surface modifier. Some examples of the most interesting capabilities provided by graphene based (bio) electrodes to the electrochemical detection of analytes and to other bioelectronic affinity assays (e.g., DNA hybridization and immuno-assays) will be discussed along with future prospects and challenges.
In this chapter we will discuss some of the most promising label-free technologies with significant impact on the field of biosensing and diagnostics, namely, conventional surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR) and nanostructure SPR arrays. Development of SPR biosensing technology is focused on improving sensitivity, miniaturizing the sensor system, tuning the operation range and high throughput detection [5]. We will discuss plasmonic-based biosensors and their integration with microfluidic chip. The application of SPR sensing platforms integrated with microfluidic chips for detection of nucleic acid and cells will be described in detail. Lastly, we will describe the current state of the art of plasmonic biosensors and give a perspective on the future of this technology for POC diagnostics.
In this chapter, short description of concept being a basis of the method, SPR systems classification, methods for sensor surface functionalization are given; structure of present-day SPR-sensors market is described. Special attention is paid to methods of SPR-sensors miniaturization and to assessment of these methods efficiency for medical applications, including prospects of SPR-sensors use for on-site diagnostics.
Oxidative stress (OS) is the imbalance between oxidant producing system and antioxidant defense mechanism resulting in an excessive production of reactive oxygen species (ROS) [1]. Under normal physiological conditions aerobic cells use oxygen as terminal electron acceptor in electron transport chain (ETC) in mitochondria. Mitochondria are the greatest source of ROS [2]. OS is widely recognized as a central feature of many biological processes and diseases, due to their impact on cell injury and death, being involved in aging, neurodegenerative disease, such as Alzheimer's and Parkinson's, neuropsychiatric diseases such as schizophrenia, bipolar, major depressive disorder, cancer [3]. Oxidative adducts derived from carbohydrates, proteins, lipids and DNA, are widely used to measure OS level in biological samples. This includes malonaldehyde (MDA), which is an indicator of lipid peroxidation [4], reduced glutathione (GSH) as an antioxidant and 8-hydroxy2'-deoxyguanosine (8OHdG) as an indicator of DNA oxidation. Nowadays, the methods used to quantify biomarkers involve complex, expensive and nonportable techniques, which impair a more effective utilization of OS biomarkers as a predictive tool for disease installation.
A myriad of assay formats are available for nanobiosensing applications. The key to select a particular one is based on the requirement of target detection. When sensitivity is of primary concern, the fluorescence and DLS methods usually offer lower detection limits than the colorimetric and refractive index sensing. SERS can even detect at single molecule level. In terms of simplicity and reliance on equipment, the colorimetric method outperforms DLS and SERS since it can be viewed by even the naked eyes. It might be noteworthy to highlight that metal NCs which represent a new class of fluorophore has the potential to outperform the conventional organic dyes in fluorescence-based nanobiosensors development.
Advances in CNMs-based biosensors are growing so quickly that we are not able to introduce all the perspectives in this field. In this chapter, we only pay particular attention to the recent technique developments in single-walled carbon nanotubes (SWNTs) and graphene-based biosensors and focus on the introduction of their in vitro and in vivo applications.
This chapter deals with the application of NMs mainly Au NPs for the sensing of oligonucleotides and proteins. The chapter is not an exhaustive review of all the NM-based sensors for biomolecules reported till date. However, this provides information on the few of the different types of NM-based nanosensors developed for sensing of nucleic acids and proteins.
