Guest Editor [s]: Shantanu Bhattacharya,3 Avinash Kumar Agarwal,4 Nripen Chanda,5 Ashok Pandey,6 and Ashis Kumar Sen7
3Department of Mechanical Engineering, Indian Institute of Technology Kanp Mechanical Engineering, Kanpur, Uttar Pradesh India
4Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh India
5Microsystem Technology Laboratory, CSIR-Central Mechanical Engineering Research Institute, Durgapur, West Bengal India
6Department of Biotechnology, CSIR-Indian Institute of Toxicology Research, Mohali, Punjab India
7Department of Mechanical Engineering, Indian Institute of Technology Madras Department of Mechanical Engineering, Chennai, Tamil Nadu India
Shantanu Bhattacharya, Phone: +91910512-259-6056, Email: ni.ca.ktii@scattahb.
Abstract
Nanofabrication has been a critical area of research in the last two decades and has found wide-ranging application in improvising material properties, sensitive clinical diagnostics, and detection, improving the efficiency of electron transport processes within materials, generating high energy densities leading to pulse power, novel therapeutic mechanisms, environmental remediation and control. The continued improvements in the various fabrication technologies have led to realization of highly sensitive nanostructure-based devices. The fabrication of nanostructures is in principle carried out primarily using top-down or bottom-up approaches. This chapter summarizes the important bottom-up nanofabrication processes for realizing nanostructures and also highlights the recent research conducted in the domain of therapeutics and diagnostics.
Keywords: Nanofabrication, Bottom-up approach, Diagnostics and therapeutics
Introduction
Nanotechnology can be defined as the design, characterization, and fabrication of engineered nanostructures or nanodevices with at least one dimension less than 100 nm [Biswas et al. ; Abu-Salah et al. ; Wang et al. ]. A reduction in the overall size of a structure to the nanometer scale results in a substantial change in its properties, e.g., chemical, physical, thermal, mechanical, which may differ entirely from their macroscale equivalents. These nanoparticles possess a high surface-to-volume ratio providing higher binding site density for the adsorption of various biomolecules [Arruebo et al. ]. Nanoparticles conjugated with antibodies or other biological moieties [e.g., low molecular weight ligands, peptides, proteins, DNA, plasmids] provide highly specific and selective recognition characteristics. One of the distinguished features of nanoparticles is the variation of their physical or chemical properties dependent on their size and shape. For example, by varying the size of metal nanoparticles their radiation and excitation wavelength can be tuned. This unique characteristic can be attributed to an optical phenomenon known as localized surface plasmon resonance [LSPR]. LSPR occurs due to the interaction of the incident light with the surface electrons present in the conduction band [Petryayeva and Krull ]. The phenomenon is generated by entrapped light waves in the conductive metal nanoparticles. Hence, nanoparticles offer specific physical and chemical properties that enable their utilization in a variety of domains like biomedical, energy and environment, manufacturing.
In general, there are three broad classifications of nanomaterials that are, natural,incidental and engineered [Hu et al. ]. Natural nanomaterials are formed through natural processes and are governed by natural laws. Incidental nanomaterials are the by-products of industries [e.g., coal dust, particulates]. Engineered nanomaterials are complex in shape and require specific processes for their fabrication. Based on the number of dimensions of the features, these nanomaterials can be classified into four types: 0-D, 1-D, 2-D, and 3-D [Chopra et al. ; Ciesielski et al. ; Pashchanka et al. ; Song et al. ]. Zero-dimensional nanostructured materials have nanoscale dimensions in all directions, e.g., nanoparticles, nanospheres, quantum dots. One-dimensional nanostructures have non-nanoscale dimensions in a single direction such as nanorods, nanotubes, nanowires, nanobelts, nanoribbons, nanostars [Kumar et al. ]. Two-dimensional nanostructures possess two dimensions having non-nanometric size range, e.g., graphene nanosheets, nanoplates, nanobelts, nanodiscs. Three-dimensional nanostructures contain non-nanoscale features in any three dimensions, e.g., nanotetrapods, nanoflowers, nanocombs.
This chapter presents a brief review of the bottom-up fabrication techniques used for fabrication of different shaped nanostructures and nanocomposites. It also covers the recent advancements in fabrication of ZnO-based nanostructures, DNA-based nanostructures, polymer-based nanostructures, and metal-based nanostructures and their widespread applications in the field of diagnostics, therapeutics, and others.
Fabrication Techniques
Nanostructures, nanomaterials, and nanocomposites can be fabricated using two different techniques, top-down and bottom-up [Bellah et al. ]. The top-down approach involves lateral patterning of bulk materials by either subtractive or additive methods to realize nano-sized structures. Several methods are used to fabricate nanostructures using the top-down approach such as photolithography, scanning lithography, laser machining, soft lithography, nanocontact printing, nanosphere lithography, colloidal lithography, scanning probe lithography, ion implantation, diffusion, deposition. [Chi ; Kumar et al. ]. Although the top-down approach has been playing a vital role in the fabrication of nanostructures, it has several limitations such as development of imperfections in processed materials, high cost [lithographic processes], requirement of high surface finished materials, longer etching times. [Mijatovic et al. ; Biswas et al. ]. In the bottom-up approach, nanostructures are fabricated by building upon single atoms or molecules. In this method, controlled segregation of atoms or molecules occurs as they are assembled into desired nanostructures [2–10 nm size range]. In general, there are two basic methods utilizing the bottom-up approach, i.e., gas-phase synthesis and liquid-phase formation. Some of the methods used in bottom-up approach include plasma arcing, chemical vapor deposition process, metal organic decomposition, laser pyrolysis, molecular beam epitaxy, solgel method, wet synthesis, and self-assembly processes.
Plasma Arcing
Plasma is one of the fundamental states of matter comprising of electrons and molecules in ionic states. It maintains a condition of overall neutrality, although there may be a net positive or negative charge on certain particles. Plasma arcing method requires an ionized state of gas atoms, for which high energy is necessary to peel off the electron from its valence shell to obtain a positively charged atom. An electrical arrangement consisting of an anode and cathode is developed providing sufficient amount of electric field to transform the atoms into ions. Electrodes used are usually made up of conducting materials or mixtures of conducting and non-conducting materials. Generation of contracted plasma uses inert gas as a heat source. Emission of electrons takes place from one electrode due to the presence of high potential difference causing an electrical breakdown. A sudden avalanche of electrons results in the formation of an arc in the zone between the electrodes. Positively charged ions travel at a high velocity and are driven by the applied bias voltage toward the cathode and get deposited as nanoparticles. It is ensured that the depth of deposition consists of a few layers of atoms with each particle of the order of more than 1 nm and all particles so formed are mutually separated. The average temperature of the arc in cold plasmas is generally higher than 104 K.
Chemical Vapor Deposition [CVD]
Chemical vapor deposition process is mostly used in the semiconductor industry for depositing thin films of various materials. The process involves exposure of the substrate to one or more volatile precursors. These precursors decompose the substrate and react with it to produce the desired deposit. In the process, vaporized precursors are first adsorbed onto a substrate at a high temperature, which then react with one another or decompose and produce crystals. There are three main steps involved in the process: [i] Reactants are transported onto the growth surface by a boundary layer, [ii] chemical reactions take place on the growth surface, and [iii] by-products formed by the gas-phase reaction are removed from the growth surface. Homogeneous nucleation takes place in gas phase, whereas heterogeneous nucleation takes place in the substrate.
Molecular Beam Epitaxy [MBE]
Molecular beam epitaxy is a physical evaporation process with no chemical reactions involved. The basic difference between MBE and other epitaxy systems is that the former does not involve any chemical reactions and is instead a simple physical evaporation process. This method works on the principle of vacuum evaporation where thermal molecular and atomic beams are directly impinged on a heated substrate under ultra-high vacuum conditions [Cho and Arthur ]. The first major advantage of the MBE process is it being a comparatively low-temperature process as compared to vapor phase epitaxy. The low-temperature characteristic of this process enables it to reduce autodoping. The second advantage of MBE is that one can have precise control over the doping process. One can achieve a growth rate as low as 0.01 µm per minute up to a maximum of 0.3 µm per minute, allowing for ultra-precise control of layer growth. With the advent of VLSI technology, it is critical to reduce all dimensions to atomic levels and thus the thickness of the epitaxial layer may also reduce further in future.
Solgel Synthesis
In the solgel process, dispersed solid nanoparticles [sols with diameter of 1–100 nm] are mixed in a homogeneous liquid medium and agglomerated to form a continuous three-dimensional network [gel] with pore diameter in the sub-micrometer domain in the liquid phase [Hench and West ]. A sol is a liquid in which solid colloidal particles are dispersed, e.g., black inkjet ink [carbon black is dispersed in water], while a gel is a wet solid-like rigid network of interconnected nanostructures in a continuous liquid phase. Generally, there are three approaches that have been employed to fabricate solgel film: [i] gelation of a solution of solid colloidal particles, [ii] hydrolysis and polycondensation of alkoxides followed by hypercritical drying of gels, and [iii] hydrolysis and polycondensation of alkoxide followed by aging and drying under ambient conditions. Several steps are involved in the process like mixing [formation of suspended colloidal solution by mixing of nanoparticles in water], casting of sol, gelation [formation of three-dimensional network], aging [for increasing the life of cast objects immersed in liquid], drying [removal of liquid from the interconnected continuous pore network], dehydration or chemical stabilization [to improve stability], and densification [heating the solgel at higher temperatures to eliminate pores and enhance the density, e.g., densification of alkoxide gels carried out at a temperature of 1000 ℃] [Hench and West ]. The properties of solgels depend on important parameters such as pH, type of solvent, temperature, time, catalysts and agitation mechanisms.
Molecular Self-Assembly
In general, four strategies are used for chemical synthesis of nanoparticles, i.e., sequential chemical synthesis, covalent polymerization, self-organizing synthesis, and molecular self-assembly. Molecular self-assembly [MSA] process is an ensemble of the properties of each of the above methods. MSA is a process in which atoms or molecules assemble together in equilibrium conditions to form a stable and well-defined nanophase by non-covalent bonds [Whitesides et al. ]. All natural materials [organic or inorganic] are processed through a self-assembly route; e.g., in a natural biological process, a DNA double helix is formed through self-assembly. This approach can be used as a basic structuring mechanism to fabricate complex nanostructures [Mijatovic et al. ]. The molecular self-assembly process is highly capable of fabricating nanostructures in the range of 1–100 nm. In order to create complex nanostructures using self-assembly process, critical parameters such as, the well-defined geometry and the specific interactions between the basic units requisite significant consideration [Rothemund ].
DNA Nanotechnology
Deoxyribonucleic acid [DNA] nanotechnology is the method to fabricate artificial nucleic acid nanostructures which can be utilized as nanofilters, biological scaffolds, fast performing nanowire devices, etc. Owing to its excellent physical and chemical properties, DNA has become the most widely used material for construction of nanostructures. Using nucleotide sequence-directed hybridization, DNA is able to produce duplexes and other secondary structures [Feldkamp and Niemeyer ]. This property allows DNA molecules to self-assemble and formulate nanoscale structures which can be employed in scaffolds, nanostructures, and nanodevices. DNA nanotechnology also utilizes the self-recognition properties of a DNA molecule to fabricate nanostructures in a desirable manner. A novel approach known as ‘the DNA origami method’ has been developed to fabricate two-dimensional DNA nanostructures of arbitrary shapes [Rothemund ].
Design and Synthesis of Nanostructures
ZnO-Based Nanostructures
In the recent years, various metal and metal oxide nanoparticles [MONPs] have been synthesized. Among these nanomaterials, the synthesis of metal oxides, especially zinc oxide, tin oxide, titanium dioxide nanostructures has been very prominent. The zinc oxide system in particular has shown many diverse applications owing to its relatively high and customizable band gap. Zinc oxide has been exploited for various applications like sensors [gas, bio, chemical, visible light, and ultraviolet], cosmetics, optical devices, optoelectronic devices, electrical devices, photochemical applications, solar cells, light-emitting displays, optical storages, drug delivery systems. [Gupta et al. , , , ; Kumar et al. ; Yao et al. ; Vaseem et al. ; Tian et al. ]. ZnO is a semiconductor with a wide band energy gap of 3.37 eV at room temperature and a binding energy of 60 meV [Djurišić et al. ; Kumar et al. ]. The crystalline structure of ZnO is wurtzite containing hexagonal unit cells. ZnO nanostructures provide large surface area, high aspect ratio, high catalytic activity, and higher number of adsorption sites on their surfaces [Chen and Tang ]. Also, a numerous variety of electronic and optical properties can be obtained using different ZnO nanostructures because of their rich defect chemistry [Djurišić et al. ].
Several fabrication techniques have been described in the literature for fabrication of ZnO nanostructures, such as sputtering, laser ablation, molecular beam epitaxy, physical vapor deposition, thermal evaporation, electrochemical deposition, template-based synthesis, and solgel methods [Yao et al. ; Wu et al. ; Chiou et al. ; Sun et al. ; Huang et al. ; Heo et al. ; Zhang et al. ]. A variety of ZnO nanostructures such as nanoparticles [Kumar et al. ], nanowires [Baruah et al. ; Vayssieres ], nanoseeds [Gupta et al. ], nanorods [Vayssieres ], nanocombs [Huang et al. ], nanobelts [Fig. 1] [Sun et al. ], nanotubes [Sun et al. ], tetrapods [Qiu and Yang ], ribbons [Fan et al. ], nanopropellers [Fig. 2] [Gao and Wang ] have been fabricated using some of the above-mentioned fabrication technologies. ZnO quantum dots have also been fabricated for applications in bacteria diagnosis [Chen et al. ] and electrochemical cells [Daumann et al. ]. Scanning electron microscopy images of a few of the above morphologies of ZnO nanostructures are shown in Fig. 3.
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a–d Image of ZnO helical nanobelts as shown in scanning electron microscope. Reproduced from Kong and Wang [], with permission from American Chemical Society
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a–d ZnO nanopropeller arrays as seen through a scanning electron microscope. Reproduced from Gao and Wang [], with permission from AIP Publishing LLC
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FESEM images of various ZnO nanostructures morphologies at different concentrations of Zn[NO3]2. Reproduced from Gupta et al. [], with permission from Royal Society of Chemistry
Polymer-Based Nanostructures
Polymers are the most extensively used biomaterials in the medical field for applications in implantation, medical devices, medical coatings, tissue engineering, and prostheses, owing to their biocompatibility with human tissues and cells [Jagur-Grodzinski ]. Polymers are generally categorized as natural or synthetic [Broz ]. Natural polymers extracted from the Mother Nature are biodegradable and offer excellent biocompatibility. Silk, wool, proteins [Dutta et al. ] [e.g., collagen, gelatin], cellulose, and DNA are some examples of naturally occurring polymers. Due to their complex structures, modification of natural polymers is challenging. While synthetic polymers are fabricated using petroleum oils as the main constituent, there are mainly four types of synthetic polymers which include thermoplastics, thermosets, elastomers, and synthetic fibers [Peacock ]. Examples of synthetic polymers include polydimethylsiloxane [PDMS], nylon, polypropylene, polyvinyl chloride, polystyrene, Teflon.
The fabrication methods of polymer nanostructures can be divided into two groups, template-based synthesis and template-free synthesis. Template-based synthesis includes conventional hard-template method [Parthasarathy and Martin ; Martin ; Yin and Zheng ], soft-template method [Meng et al. ], and novel wire-template method [e.g., water soluble templates, reactive self-degraded wire templates, seeding wire templates, biological wire templates] [Liang et al. ]. On the other hand, template-free synthesis includes self-assembly method [Wan ], electrospinning [Li and Xia ], and nanoscale patterning. Template-based synthesis employs nanostructured matters as templates, over which one-dimensional polymer nanostructures can be grown. In a conventional hard-template method, micro-/nanoporous membrane materials, e.g., anodic aluminum oxide and particle track-etched membranes, are used as templates. The growth of polymer nanostructures takes place due to an electrochemical reaction of the loaded monomer solutions within the pores of these templates [Martin ]. Reaction rate, reaction time, and temperature are vital parameters for controlling the growth of these nanostructures using conventional hard-template methods. In soft-template methods, soft amphiphilic materials like liquid crystals, surfactants, copolymers are utilized as templates. The formation of polymer nanostructures takes place as a result of the aggregation of self-assembled amphiphilic molecules through hydrogen bonding, hydrophilic–hydrophobic interactions and Van der Waals forces [Han and Foulger ]. Novel wire-template methods are superior compared to hard-template and soft-template methods because they possess combined properties of both the above methods [Liang et al. ]. The fabricated polymer nanostructures by this process possess high stability. In this process, preexisting one-dimensional nanomaterials are used as templates over which 1D polymer nanocomposites are grown. Template-free methods do not require any templates. Self-assembly is extensively used as a template-free chemical method for fabrication of nanostructures. Polymer nanostructures form by aggregation of nanoparticles through non-covalent bonding such as dipole–dipole interaction, electrostatic interaction, Van der Waals forces, ion–dipole interactions, and π-π stacking. Electrospinning is also a template-free physical method, in which a very high electric field is applied between the syringe containing the polymeric fluid and a conductive collector screen. A liquid jet forms when the applied electric field surpasses the surface tension of the polymeric fluid and accelerates toward the counter electrode. During this movement, the liquids get solidified and accumulate as nanofibers over the collector. Several researchers have reported the fabrication of various polymer nanostructure morphologies. Epoxy-based SU-8 polymer nanostructures with tunable high aspect ratios have been fabricated using electron beam lithography [Beckwith et al. ]. These nanostructures were synthesized on glass cover slips. Uniform arrays of SU-8 nanopillars and nanolines are shown in Fig. 4.
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SEM images of a nanopillars and b nanolines. Reproduced from Beckwith et al. [], with permission from the Royal Society of Chemistry
Ferroelectric polymer nanostructures have also been synthesized using flexible polyethylene terephthalate substrates [Song et al. ]. A low-pressure reverse nanoimprint lithography technique has been developed that uses soft polycarbonate molds derived from recordable DVDs to fabricate nanostructures. These nanostructures are highly stable and exhibit switchable piezoelectric response and good crystallinity.
Metal-Based Nanostructures
Recently, many research fields have focused on the development of metallic nanostructures with complex shapes and various compositions in order to exploit their distinctive qualities [Gentile et al. ; Xia et al. ]. Due to the high surface-to-volume ratios, metal-based nanostructured materials have been used in various domains such as catalysis, sensing, fuel cells, mechanical actuators, electrodes, point-of-care diagnostics, medicine. [Gentile et al. ; Jiang et al. ].
Various metallic nanostructures have been reported such as porous nanowires [Kolmakov et al. ], porous nanotubes [Lévy‐Clément et al. ], porous nanosheets [Liang et al. ; Zhang et al. ], quantum dots [Abeyasinghe et al. ; Lian et al. ], hollow and porous nanospheres [Zhang et al. ]. Figures 5 and 6 show SEM and TEM images of some nanowires and nanospheres.
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a SEM images of silver nanowires synthesized with different amounts of FeCl3: a 0.05 mM, b 0.10 mM, and c 0.15 mM. Adapted from Ma and Zhan [], with permission from the Royal Society of Chemistry. d TEM image of a typical silver nanowire. Reproduced from Hu et al. [], with permission from the Royal Society of Chemistry
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a SEM image of CuO nanospheres. The inset shows the image at a higher resolution, b transmission electronic microscope image of the CuO nanospheres with an inset depicting the ED pattern of one nanosphere. Reproduced from Zhang et al. [], with permission from American Chemical Society
Monodispersed bismuth particles have been fabricated by thermally decomposing bismuth acetate in boiling ethylene glycol [Wang and Xia ]. The size of the nanospheres was varied by varying the concentration of the bismuth precursor and the stirring rate. The respective SEM and TEM images of the nanospheres are shown in Fig. 7.
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a SEM image of bismuth nanospheres. Inset: higher resolution image, b TEM image of the bismuth nanospheres. Inset: SAED pattern of one nanosphere. Reproduced from Wang and Xia [], with permission from American Chemical Society
Platinum nanocrystals have been synthesized using a liquid–liquid-phase transfer method [Demortiere et al. ]. By controlling the nucleation and growth process parameters, cubic and pyramidal morphologies have been achieved [Fig. 8]. Further, the nanocrystals self-assemble to develop 2D and 3D supracrystals.
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a, b SEM image of cubic-shaped superlattices obtained from platinum nanocubes, c, d SEM images of pyramidal-shaped superlattices obtained from truncated nanocubes. Reproduced from Demortiere et al. [], with permission from American Chemical Society
A soft–hard-template method has been employed for fabrication of monodispersed carbon dots [Yang et al. ]. In order to obtain different sizes, compositions, and crystallinity, four different precursors have been used that include pyrene [PY], 1,3,5-trimethylbenzene [TMB], phenanthroline [PHA], and diaminebenzene [DAB]. The TEM images of the as-synthesized carbon dots have been shown in Fig. 9.
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HRTEM images of carbon dots using different precursors: a TMB, b DAB, c PY, and d PHA. Insets show the magnified HRTEM images. Reproduced from Yang et al. [], with permission from the Royal Society of Chemistry
DNA-Based Nanostructures
Deoxyribonucleic acid [DNA] is a genetic molecule in which hereditary information is encoded. It has an antiparallel double-stranded helical structure which enables its use in fabrication of nanostructures and nanodevices through a self-assembly process [Seeman ; Sun and Kiang ; Yan et al. ]. The diameter of each strand of DNA is about 2 nm, and the helical pitch is about 3.5 nm. DNA is composed of a nitrogen-containing nucleobase [adenine, cytosine, guanine, and thymine], a sugar molecule, and a phosphate group. It has several specific characteristics that make it a preferable choice for fabrication of engineered biological nanostructures. First, DNA molecules segregate by self-assembly process so that complex structures can be fabricated with a nanometer resolution [Yan et al. ]. Second, since the genetic information is encoded by chemical coding process, the intermolecular interaction of molecules can be easily programmed [Sun and Kiang ]. Third, although double-stranded DNA [dsDNA] is a flexible polymer, it acts as a rigid polymer below the 50 nm size [Feldkamp and Niemeyer ]. Therefore, the nanostructures [