Biosensors and Nanotechnology

Applications in Health Care Diagnostics

Zeynep Altintas, Zeynep Altintas

• Publisher: Wiley
• Year: 2017
• ISBN:
  9781119065173
• Edition: 1
• Topic: Technologie et ingénierie
• Subtopic: Nanotechnologie et MEMS

Provides a broad range of information from basic principles to advanced applications of biosensors and nanomaterials in health care diagnostics

This book utilizes a multidisciplinary approach to provide a wide range of information on biosensors and the impact of nanotechnology on the development of biosensors for health care. It offers a solid background on biosensors, recognition receptors, biomarkers, and disease diagnostics. An overview of biosensor-based health care applications is addressed. Nanomaterial applications in biosensors and diagnostics are included, covering the application of nanoparticles, magnetic nanomaterials, quantum dots, carbon nanotubes, graphene, and molecularly imprinted nanostructures. The topic of organ-specific health care systems utilizing biosensors is also incorporated to provide deep insight into the very recent advances in disease diagnostics.

Biosensors and Nanotechnology: Applications in Health Care Diagnostics is comprised of 15 chapters that are presented in four sections and written by 33 researchers who are actively working in Germany, the United Kingdom, Italy, Turkey, Denmark, Finland, Romania, Malaysia and Brazil. It covers biomarkers in healthcare; microfluidics in medical diagnostics; SPR-based biosensor techniques; piezoelectric-based biosensor technologies; MEMS-based cell counting methods; lab-on-chip platforms; optical applications for cancer cases; and more.

• Discusses the latest technology and advances in the field of biosensors and their applications for healthcare diagnostics
• Particular focus on biosensors for cancer
• Summarizes research of the last 30 years, relating it to state-of-the-art technologies

Biosensors and Nanotechnology: Applications in Health Care Diagnostics is an excellent book for researchers, scientists, regulators, consultants, and engineers in the field, as well as for graduate students studying the subject.

Section 1
Introduction to Biosensors, Recognition Elements, Biomarkers, and Nanomaterials

1
General Introduction to Biosensors and Recognition Receptors

Frank Davis¹ and Zeynep Altintas²

¹ Department of Engineering and Applied Design, University of Chichester, Chichester, UK

² Technical University of Berlin, Berlin, Germany

1.1 Introduction to Biosensors

There are laboratory tests and protocols for the detection of various biomarkers, which can be used to diagnose heart attack, stroke, cancer, multiple sclerosis, or any other conditions. However, these laboratory protocols often require costly equipment, and skilled technical staff, and hospital attendance and have time constraints. Much cheaper methods can provide cost‐effective analysis at home, in a doctor’s surgery, or in an ambulance. Rapid diagnosis will also aid in the treatment of many conditions. Biosensors generically offer simplified reagentless analyses for a range of biomedical [1–8] and industrial applications [9, 10]. Due to this, biosensor technology has continued to develop into an ever‐expanding and multidisciplinary field during the last few decades.

The IUPAC definition of a biosensor is “a device that uses specific biochemical reactions mediated by isolated enzymes, immunosystems, tissues, organelles or whole cells to detect chemical compounds usually by electrical, thermal or optical signals.” From this definition, we can gain an understanding of what a biosensor requires.

Most sensors consist of three principal components:

1. Firstly there must be a component, which will selectively recognize the analyte of interest. Usually this requires a binding event to occur between the recognition element and target.
2. Secondly some form of transducing element is needed, which converts the biochemical binding event into an easily measurable signal. This can be a generation of an electrochemically measurable species such as protons or H₂O₂, a change in conductivity, a change in mass, or a change in optical properties such as refractive index.
3. Thirdly there must be some method for detecting and quantifying the physical change such as measuring an electrical current or a mass or optical change and converting this into useful information.

There exist many methods for detecting binding events such as electrochemical methods including potentiometry, amperometry, and AC impedance; optical methods such as surface plasmon resonance; and piezoelectric methods that measure mass changes such as quartz crystal microbalance (QCM) and surface acoustic wave techniques. A detailed description of these would be outside the remit of this introduction, but they are described in many reviews and elsewhere in this book. Instead this chapter focuses on introducing the recognition receptors used in biosensors.

1.2 Enzyme‐Based Biosensors

Leyland Clark coated an oxygen electrode with a film containing the enzyme glucose oxidase and a dialysis membrane to develop one of the earliest biosensors [11]. This could be used to measure levels of glucose in blood; the enzyme converted the glucose to gluconolactone and hydrogen peroxide with a concurrent consumption of oxygen. The drop in dissolved oxygen could be measured at the electrode and, with careful calibration, levels of blood glucose calculated. This led to the widespread use of enzymes in biosensors, mainly driven by the desire to provide detection of blood glucose. Diabetes is one of the major health issues in the world today and is predicted to affect an estimated 300 million people by 2045 [12]. The world market for biosensors was approximately $15–16 billion in 2016. In 2009 approximately half of the world biosensor market was for point‐of‐care applications and about 32% of the world commercial market for blood glucose monitoring [13].

Enzymes are excellent candidates for use in biosensors, for example, they have high selectivities; glucose oxidase will only interact with glucose and is unaffected by other sugars. Being highly catalytic, enzymes display rapid substrate turnovers, which is important since otherwise they could rapidly become saturated or fail to generate sufficient active species to be detected. However, they demonstrate some disadvantages: for instance, a suitable enzyme for the target of interest may simply not exist. Also enzymes can be difficult and expensive to extract in sufficient quantities and can also be unstable, rapidly denaturing, and becoming useless. They can also be subject to poisoning by a variety of species. Moreover, detection of enzyme turnover may be an issue, for instance, in the glucose oxidase reaction; it is possible to directly electrochemically detect either consumption of oxygen [11] or production of hydrogen peroxide. However in samples such as blood and saliva, there can be other electroactive substances such as ascorbate, which also undergo a redox reaction and lead to false readings. These types of biosensors are often called “first‐generation biosensors.” To address this issue of interference, a second generation of glucose biosensors was developed where a small redox‐active mediating molecule such as a ferrocene derivative was used to shuttle electrons between the enzyme and an electrode [14]. The mediator readily reacts with the enzyme, thereby avoiding competition by ambient oxygen. This allowed much lower potentials to be used in the detection of glucose, thereby reducing the problem of oxidation of interferents and increasing signal accuracy and reliability. Figure 1.1 shows a schematic of a second‐generation glucose biosensor.

Figure 1.1 Schematic of a second‐generation biosensor.

Third‐generation biosensors have also been developed where the enzyme is directly wired t...