General Introduction

In Figure 2.1, three main disciplines including chemistry, materials science and biotechnology are presented. Merging these disciplines will allow us to take advantage of the improved evolutionary biological components to generate new smart materials and to apply today’s advanced materials and physicochemical techniques to solve biological problems.

Both biotechnology and materials science meet at the same length scale (Figure 2.2). On the one hand, biomolecular components have typical size dimensions in the range of about 5 to 200 nm. On the other hand, commercial requirements to produce increasingly miniaturized

microelectronic devices strongly motivate the elaboration of nanoscale systems [3]. Today’s nanotechnology research puts a great emphasis on the development of bottom-up strategies, which concern the self-assembly of (macro) molecular and colloidal building blocks to create larger, functional devices [4]. Novel nanomaterials for use in bioassay applications represent a rapidly advancing field. Various nanostructures have been investigated to determine their properties and possible applications in biosensors. These structures include nanoparticles, nanowires, nanotubes, and thin films. Functional nanoparticles (electronic, optical and magnetic) bound to biological molecules have been developed for use in biosensors to detect Figure 2.1: Chemistry is the central science for the development of applied disciplines

such as materials research and biotechnology. Materials science, which is based on classic chemical research fields and engineering technologies, has led to enormous advances in tailoring advanced modern materials [3].

and amplify various signals [5-9]. The interdisciplinary cooperation of various techniques can solve the human-related diseases.

Colloidal quantum dots are the size of a typical protein, and thus it should be possible to introduce colloidal quantum dots into cells. In 1998, colloidal quantum dots have first been

Figure 2.3: Cell labeling with quantum dots and illustration of quantum dot photostability, compared with the dye Alexa 488. In the upper panels, the nucleus is stained red with quantum dots and the actin fibers are stained green with the dye. In the lower panel, the labeling is reversed.

Figure 2.2: A gap currently exists in the engineering of small-scale devices. Whereas conventional top-down processes hardly allow the production of structures smaller than about 100-200 nm, the limits of regular bottom-up processes are in the range of about 2-5 nm [3].

used for biological labeling [10-11]. It suggested that the photochemical stability and the ability to tune broad wavelength of the quantum dots may make these materials extremely useful for biolabeling (Figure 2.3) [12]. Colloidal quantum dots are robust and very stable light emitters and they can be broadly tuned simply through size variation. In the past few years, a wide range of methods for bio-conjugating colloidal quantum dots was developed [13].

In Figure 2.4, boron-doped silicon nanowires (SiNWs) were reported to create highly sensitive, real-time electrically based sensors for biological and chemical species. The amine and oxide-functionalized SiNWs exhibited pH-dependent conductance that was linear over a large dynamic range and could be understood in terms of the change in surface charge during protonation and deprotonation. Biotin-modified SiNWs were used to detect streptavidin down to at least a picomolar concentration range. In addition, antigen-functionalized SiNWs showed reversible antibody binding and concentration-dependent detection in real time. The small size and capability of these semiconductor nanowires for sensitive, label-free, real-time detection of a wide range of chemical and biological species can be exploited in array-based screening and in vivo diagnostics [14].

Figure 2.4: Nanowire-based electrical biosensors. (a) Scheme showing silicon nanowires functionalized with biotin. (b) On exposure to streptavidin, the nanowires show changes in conductivity. Plot of conductance versus time for a biotin-modified SiNW, where region 1 corresponds to buffer solution, region 2 corresponds to the addition of 250 nM streptavidin, and region 3 corresponds to pure buffer solution. (c) A nanowire that is not functionalized with biotin shows no response. Conductance versus time for an unmodified SiNW; regions 1 and 2 are the same as in b. [14]

Carbon nanotubes have attracted great attentions as nanoscale building blocks for devices.

The nano-dimensions, graphitic surface chemistry and electronic properties of carbon nanotubes make them an ideal material for use in chemical and biochemical sensing (Figure 2.5) [15, 16]. Semiconductor nanowires and carbon nanotubes offer the greatest chance yet for creating robust, sensitive, and selective electrical detectors of biological binding events.

Nanofabrication processes typically use variations of the four basic operations of photolithography, thin film growth/deposition, etching, and bonding to create nanometer-sized objects. Nano-electromechanical system (NEMS) technologies are used to produce complex electrical, mechanical, fluidic, thermal, optical, and magnetic structures, devices, and systems with characteristic sizes down to nanometers. NEMS creates and uses systems that have novel properties and functions because of their small and/or intermediate size. DNA hybridization and receptor–ligand binding to microfabricated cantilevers produce surface stress changes that have been measured directly for detection of analytes. A biosensor is made by functionalizing one side of the cantilevers with receptor molecules and then detecting the mechanical bending induced by the binding of a ligand [17].

Nanotechnology is revolutionizing the development of biosensors. Nanotechnology-based Figure 2.5: Nanotube-based electrical biosensors. (a) Scheme showing nanotubes

functionalized with biotin. (b) Quartz-based microbalance signal of nanotubes after addition of different concentrations of streptavidin. (c)Electrical signal of nanotubes after addition of different concentrations of streptavidin [16].

(a) (b) (c)

biosensors should be integrated within tiny biochips with on-board electronics, sample handling and analysis. This will greatly enhance functionality, by providing devices that are small, portable, easy to use, low cost, disposable, and highly versatile diagnostic instruments.