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Opportunities and Challenges of Biosensors Based on Nanomaterials and Nanodevices
Jun Li and Nianqiang (Nick) Wu
CONTENTS
1.1 Introduction
1.2 Principles of Biosensors
1.3 Functionalization of Nanomaterials and Immobilization of Biomolecules
1.4 Application of Nanomaterials and Nanostructures in Biosensors
1.5 Biosensing Mechanisms and Organization of the Book
1.5.1 Section I: Optical Biosensors
1.5.2 Section II: Electrical Biosensors
1.5.3 Section III: Magnetic Nanoparticles for Biosensing and Cancer Treatment
1.5.4 Section IV: Biosensors Based on Thermal Properties
1.6 Device Integration
1.7 Remarks on Challenges and Future Opportunities
References
1.1 Introduction
The last two decades have witnessed the explosion of nanoscience and nanotechnology. Particularly, the establishment of the National Nanotechnology Initiative (NNI) at the end of the last century has greatly stimulated research in this new field [1, 2, 3, 4 and 5]. The research efforts have produced a plethora of methods for the synthesis, characterization, computer simulating, theoretical modeling, manufacturing, and applications of nanomaterials that have at least one dimension on the nanoscale (1–100 nm). Nanomaterials with the length scale lying between that of molecules and conventional continuum materials (over microns) are in a unique state of matter [6]. They present fundamentally different physical and chemical properties and usually exhibit size- and shape-dependent interactions with electrons, photons, electromagnetic fields, etc. [7,8].
Since the size of nanomaterials is comparable to that of biomolecules, there is a great potential to probe and manipulate biological systems from the molecular level up to macroscopic tissues using nanomaterials and nanodevices [9]. This provides ample opportunities to identify the molecular origins of diseases, to develop more selective therapies, to enable health monitoring and early disease diagnosis, and to establish the knowledge base for biocompatible prosthetics and regenerative medicine [9, 10, 11 and 12]. In spite of a lot of challenges, the integration of artificial nanomaterials with natural biological systems has achieved significant accomplishments, leading to the rapid development of various nanodevices used for biomedical studies from the molecular and subcellular level to tissue engineering. This book presents the recent progress in the applications of a broad spectrum of nanomaterials in biosensors and biomedical devices based on their unique optical, electrical, magnetic, and thermal properties.
1.2 Principles of Biosensors
Biosensors are the devices or materials that respond selectively to biological targets (or analytes) via a specific molecular recognition probe (typically based on biological materials), and convert the biological recognition event into a sensing signal via a proper transducer. They can be directly used to detect and quantify specific analytes. International Union of Pure and Applied Chemistry (IUPAC) defines a biosensor as “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” [13]. The scope of the biosensors in this book is broader, as schematically illustrated in Figure 1.1. A biosensor generally consists of at least two components: (1) a molecular recognition probe that selectively interacts with biological materials, such as DNA, aptamer, antibody, ligand, enzyme, microorganism, cell, and tissue; and (2) a physicochemical transducer that converts the selective biological interaction into the physical signal based on the optical, electrical, magnetic, and thermal properties of the transducer materials. The selectivity of a biosensor mostly relies on the specificity of the molecular recognition probe derived from the biological materials. However, the sensitivity and the limit of detection of a biosensor strongly depend on the physicochemical properties of the transducer, which can be improved by the utilization of proper materials and/or the design of new device architectures. Thus, nanomaterials and nanodevices play significant roles in signal transduction.
As compared to conventional analytical instruments, biosensors are portable, miniaturized devices that are ideal for the rapid and high-throughput measurement of analytes and can even provide real-time information [14,15]. The development of biosensors has been accelerated by the increasing demands on simple, rapid, cost-effective, and portable screening methods for the qualitative and quantitative determination of analytes relevant to medical research, clinical diagnosis/treatment, environment and food safety monitoring, agricultural inspections, industrial quality control, and biosecurity investigations. The development of a biosensor requires interdisciplinary collaboration involving chemistry, physics, materials science, engineering, as well as the life sciences.
FIGURE 1.1
Schematic of the components of a biosensor.
1.3 Functionalization of Nanomaterials and Immobilization of Biomolecules
The molecular recognition probe in a biosensor is normally a biomolecule or other biological material that needs to be attached to the surface of a transducer. The bioactivity of the molecular recognition probe is strongly dependent on the immobilization method [16]. For example, the direct adsorption of an enzyme on a planar inorganic surface may cause the denaturation of the enzyme. In contrast, trapping the enzyme on the nanostructures can retain its bioactivity [16]. In addition, the sensitivity of a biosensor is affected by the immobilization method. Therefore, the immobilization of molecular recognition probes on the surface of a transducer is an important step in the construction of biosensors.
Effective strategies, including physical, covalent, and bioaffinity immobilization, have been developed, which are summarized in review articles [11,14,16] and detailed in relevant chapters. Direct adsorption of the molecular recognition probes on a large area of a flat solid surface of bulk materials not only limits the number of immobilized molecules but also does harm to the activity of biomolecules. Hence, physical immobilization is typically applied to special nanoparticles (NPs) or porous nanostructures. For example, single-stranded DNA can be simply immobilized on the surface of graphene oxide sheets via physical adsorption. Covalent linkage is a commonly used immobilization method, which enables the long-term stability of immobilized biomolecules. A flexible linker molecule is typically employed between the transducer and the molecular recognition probe in order to reduce the steric hindrance by the solid surface and to ensure that the molecular recognition probe remains the same biological activity as those in the bulk solution. The small size and large surface curvature of nanomaterials have been found to significantly reduce the steric effects compared to micro- or macro-transducers. The third immobilization method is to use biochemical affinity reactions. In particular, bioaffinity immobilization is widely used for the attachment of proteins on the transducer. The commonly used bioaffinity pairs include antibody–antigen interaction, receptor–antagonist/agonist, oligonucleotide duplex, affinity-capture ligand system, DNA-directed systems, etc. [14].
In addition, the surface of the transducers may be further passivated with some antiadsorption agents to reduce the nonspecific binding of biological analytes and biofouling by other components in the biological matrices. This needs particular attention for biosensors based on nanomaterials and nanodevices, due to their high specific surface area. Some nanomaterials (such as quantum dots (QDs) plasmonic NPs, and magnetic NPs) require a protective coating or capping agents to avoid their reaction with the solution or the leaking of toxic contents into the sample or body. Ideally, it is highly demanded in nanomedicine to combine multiple functions such as drug delivery/release, antibiofouling, specific recognition, high-contrast imaging, and therapeutic treatment into each single NP [11,17,18]. The functionalization strategies strongly depend on the surface chemical properties of the employed nanomaterials. The details are discussed under each individual chapter.
1.4 Application of Nanomaterials and Nanostructures in Biosensors
Nanomaterials generally refer to materials with at least one of their geometric dimensions falling between 1 and 100 nm. Nanomaterials and nanodevices are much more attractive as transducers than traditional micro- and macrocounterparts. First, as the particle size is reduced, the surface-to-volume dramatically increases. As a result, the interaction of the analytes with the NP-based transducer is much stronger, which causes a larger change in the physical properties of the transducers, generating a stronger signal response. Second, the nanoscale dimension of the transducer is comparable with that of biomolecules, which provides the capability of directly interacting with single molecules. Third, the new physical properties, such as the enhanced fluorescence yield of QDs and surface-enhanced Raman scattering (SERS) by plasmonic NPs, can greatly amplify the signal, leading to dramatically improved sensitivity. Fourth, the size reduction also benefits cost-saving, detection-speed improvement, sample-volume reduction, as well as increase in the degree of multiplexing degree increase, which are not achievable with conventional micro- and macrobiosensors.
Depending on the nature of the nanomaterials, different chemical and physical properties are utilized for biosensing, which will be discussed in later chapters. Here, we selectively present some representative nanomaterials according to the dimension.
Zero-dimensional (0D) nanomaterials: These are the materials whose sizes in all three dimensions are confined to the nanoscale. Important 0D nanomaterials include semiconductor nanocrystals (NCs) or QDs, metal NPs, magnetic NPs, polymer NPs, and phasechange NPs. 0D nanomaterials have a high specific surface area, in which a large number of atoms is exposed at the outer surface. In particular, they show a strong quantum confinement or other size-dependent properties. For example, the fluorescence emission of QDs can be t...