pdf -application of naotechnology
- 1. Review Article Forensic Applications of Nanotechnology Yung-fou Chen Department of Forensic Science, Central Police University, No. 56, Shujen Rd., Takang Village, Kueishan Hsiang, Taoyuan County, 33304, Taiwan, R.O.C. Received June 29, 2011; Accepted September 20, 2011; Published Online September 27, 2011 Nanotechnology has a great influence on modern technology, just like the development of DNA pro- filing on biotechnology in the past 50 years. Because of applying knowledge and techniques from natural science, forensic science aims to identify, individualize and evaluate evidence. Evidence will then be used to reconstruct crime scenes, guide investigations and bring criminals to justice. Nanotechnology has been applied towards these purposes. Among the various nanotechnologies, nano-analysis is most commonly seen in forensic science with instrumentations including transmission electron microscope (TEM), scan- ning electron microscope (SEM), atomic force microscope (AFM) and Raman microspectroscopy (Mi- cro-Raman). This paper will introduce the principles of nanotechnology, instrumentations, and known fo- rensic applications. In addition, the toxicity of nanomaterials and future prospects will be discussed. Keywords: Nanotechnology; Forensic science; Criminalistics; Atomic force microscopy (AFM); Scanning probe microscopy (SPM); Raman microspectroscopy; Nanotoxicology. INTRODUCTION Nanotechnology is making valuable contributions to various scientific fields in science and technology today. Generally, it is defined as the study, design, creation, syn- thesis, manipulation, application of functional materials, devices, and systems through control of matter at the nano- meter scale. It has been applied to many areas of study1 in- cluding electronic engineering, physical sciences, materi- als sciences, biomedical sciences and many others. Recently, many new nanoscale sample analysis tech- niques in genetic, medicine, analytical chemistry have been applied to fields of forensic sciences.2 Nanotechnology contributes to forensic sciences in two ways. Since it can detect and analyze samples in the nanoscale, critical evi- dence that could not be collected and analyzed before due to the detection limits of the instruments can now be ana- lyzed and used to support the investigations. In addition, namomaterials possess novel properties that can assist the collection and detection of evidence which cannot be ac- quired previously. Some examples include trace amounts of gunshot residues, heavy metals, explosives, DNAon fin- gerprint or palm prints, and so on. Foreign law enforcement agencies have already begun to consider sponsoring more research projects on the forensic applications of nanotech- nology. According to the National Nanotechnology Initia- tive (www.nano.gov) fiscal year 2006 budget request, the National Institute of Justice (NIJ) of United State Depart- ment of Justice (USDOJ) has two separate project areas that incorporate nanotechnology – DNA Research and De- velopment ($1.0 million) and Chemical and Biological De- fense ($1.0 million). The DNA Research and Development program consists of fundamental research and the demon- stration of chip-based or micro-device technologies to ana- lyze DNA in forensic applications. The Chemical and Bio- logical Defense program is focuses on developing a wear- able, low-cost device to provide warning of exposure to un- anticipated chemical and biological hazards in sufficient time for its wearer to take effective protective measures. The Beginning Dr. Richard Feynman first mentioned a few unprece- dented concepts in nanotechnology in his talk “There’s Plenty of Room at the Bottom” (full transcript can be found at http://www.zyvex.com/nanotech/feynman.html) in 1959. He envisioned manipulating single atom and adjacent mol- ecules by employing tools that can be precisely and accu- 828 Journal of the Chinese Chemical Society, 2011, 58, 828-835 Special issue for the nanotechnology-related analytical chemistry * Corresponding author. E-mail: nanoforensics@mail.cpu.edu.tw
- 2. rately operated at the atomic scale. For example, the writ- ing of the full volume Encyclopedia Britannica on the head of a pin becomes possible if the electron beams of electron microscopes are used backwards as a writing instrument. He also mentioned on such small scale, gravity is less im- portant while surface tension and Van der Waals attraction play more important roles. Gold is chemically inert in bulk, but is chemically catalytic at nanoscale. These are the fun- damental ideas in nanotechnology and they have begun to transform into reality since the 1980’s. United States NNI defined it as follows: “Nanotech- nology is the understanding and control of matter at dimen- sions of roughly 1 to 100 nanometers, where unique phe- nomena enable novel applications.” When materials be- come that small, their physical and chemical properties change significantly. Metallic gold is an excellent example. In a bulk sample, it has a melting point of 1064 °C, but gold nanoparticles between 1.5 to 2 nm in diameter possess melting points around 300 °C. Additionally, gold nanopar- ticles no longer posses the signature metallic shine of bulk gold, but is pink to purple color, depends on the size, and is liquid at room temperature. Other examples includes opaque copper becomes transparent; inert platinum becomes cata- lytic; stable aluminum becomes combustible (aluminum); silicon insulator becomes conductor. Other important prop- erties observed in the nanoscale are the larger relative sur- face area and the dramatic changes in electronic structures. Current known nanomaterials includes nanoparti- cles,3 quantum dots(semiconductor nanomaterials),4 car- bon nanotubes,3a,4f,5 self-assembled peptide nanotubes,6 and many others. They can be used in medicine,7 cataly- sis,3d,8 environment engineering,4f,9 communication,10 quantum computer,11 and consumer products.12 HOW TO ANALYZE NANOMATERIALS? Before further manipulations and applications, nano- materials must be characterized in order to understand their unique properties. Common techniques for analyzing nano- materials include electron microscopy (transmission elec- tron microscopy, TEM and scanning electron microscopy, SEM); atomic force microscopy (AFM); dynamic light scaterring (DLS), and Raman microspectroscopy (Mi- cro-Raman). The brief descriptions of the afromentioned instrumentations are given below. Electron Microscopy Electron microscopy magnifies very fine details of nanomaterials with the use of electron beams as the illumi- nation source, and can provide resolution in the sub-nano- meter regime. The illumination source of Transmission electron microscopy (TEM) is a high voltage electron beam emitted by a cathode that is focused by a lens. The sample is first placed under vacuum. Then the high voltage electron beam partially transmit through the sample and the trans- mitted electrons are subsequently focused and amplified. When the beam hits a phosphor screen, photographic plate, or other light sensitive sensor, an image is formed. TEM only provides two-dimensional images of the sample, but it contains information (images and diffraction patterns) regarding the inner structure of the materials. Scanning electron microscopy (SEM). SEM is very different from TEM in the way the final images are formed. While TEM detects primary electrons, SEM generates im- ages by detecting secondary or back-scattered electrons, which are emitted from the surface of a material due to ex- citation by the primary electron beam. In SEM, the electron beam is scanning across the sample, with detectors build- ing up an image by mapping the detected signals as a func- tion of beam position. Generally, the resolution limit of SEM is about 5 nm; however, because SEM images show surface morphology rather than inner structure, it can produce three-dimen- sional images of the nanomaterials. Atomic Force Microscopy (AFM) AFM is a type of high-resolution scanning probe mi- croscopy (SPM). It is a very powerful tool to analyze nano- materials. The basic components of AFM consist of a microcantilever with a very sharp probe (tip) at the end to scan the sample surface. Typically, the cantilever is made by silicon or silicon nitride. Depending on the usage, canti- lever can be coated with a thin film of gold or other metals and the tip radius is about several nm. AFM image genera- tion is based on the deflection of the forces between the cantilever tip and sample surface when brought into con- tact. The forces that can be analyzed include mechanical contact force, Wan der Waals force, capillary force, chemi- cal bonding, electrostatic force, magnetic forces, salvation force and so on.13 The deflection, which behaves via Hooke’s Law, is detected by a laser located on the top of cantilever and subsequently reflected into a photodiode ar- ray. Any tiny positional shifts of the laser spot as a result of deflection during scanning is recorded and converted into a 3-D image. In order to move the samples on the nanoscale, Forensic Applications of Nanotechnology J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 829
- 3. the sample is mounted on a piezoelectric tube (the sub- stance that produces an electric charge when it is squeezed and stretched). It then can move sample along the x and y directions for scanning the sample and the z direction for maintaining a constant force. The resulting map of s(x, y) represents the topography of the sample. Figure 1 shows the AFM image of eyebrow. Although both AFM and SEM can produce 3-D im- ages, AFM has several advantages over SEM. AFM can produce images with a lateral resolution of 0.1 nm and a vertical resolution of 0.02 nm, whereas SEM can only achieve a resolution of about 5 nm. Nanomaterials ana- lyzed by AFM do not require special sample preparations that might damage the sample. Most AFM works effi- ciently in ambient air or a liquid environment. Therefore, studies of biological macromolecules and living organisms in nanoscale are no longer a difficult task. Dynamic Light Scattering (DLS) DLS is also known as “photon correlation spectros- copy” (PCS) or “quasi-elastic light scattering” (QELS). It is a well established technique for measuring particle size over the size range from a few nanometers to a few mi- crons. The basic concept behind this technique is that since small particles move randomly in a suspension, scattered light can be used to measure the rate of diffusion of these particles, including proteins. Dynamic scattering is particu- larly good at sensing the presence of very small amounts of aggregated protein (< 0.01% by weight), as well as for the study of samples containing aggregates over a large range of sizes. The common detection range is between 0.8 to 6500 nm. Size distributions of various novel nanomaterials can easily be categorized by DLS. Raman Microspectroscopy (Micro-Raman) Raman spectroscopy differs from the rotational and vibrational spectroscopy in that it is concerned with the scattering of radiation by the sample, rather than the ab- sorption process. The energy of the excitation radiation de- termines which type of transition occurs - rotational transi- tions require lower energy excitation while higher energy radiation leads to vibrational transitions. As a result, rota- tional transitions are typically three orders of magnitude slower, making it possible for intermolecular collisions to occur. Therefore, rotational spectroscopy is carried out in the gas phase at low pressure to ensure that the time between collisions is greater than the time required for a transition. Typically, a sample is illuminated with a laser beam. Scattered light from the illuminated spot is collected with a lens and sent through a monochromator. Wavelengths close to the laser line (Raleigh scattering) will be filtered out and those in a certain spectral range (wavenumber) away from the laser line are dispersed onto a detector. Raman spec- trometers usually use holographic diffraction grating, mul- tiple dispersion prisms, a pohotomultipliertube (PMT) or charged-coupled device (CCD) camera to count photons. The advantages of Raman spectroscopy are that special sample preparation is not needed and it is non-destructive. Unlike infrared spectroscopy, the interference from water to the Raman spectrum is weak. As a result, Raman spec- troscopy is very well suited for studying cells, tissues, pep- tides, proteins and other biological entities. The biggest disadvantage of Raman spectroscopy is the strong fluores- cence interference from the sample or background. How- ever, it is possible to reduce this interference by applying a Fourier Transform to the raw data (FT-Raman). Vibrational and rotational motions of specific types of chemical bonds in organic molecules can be correlated to very specific range of energy. It provides the fingerprint by which the molecule can be identified. For organic mole- cules, the “fingerprint region” ranges from of 500-2000 cm-1 . Another way that the technique is used is to study changes in chemical bonding, such as when a substrate is added to an enzyme. The morphology and binding situation analysis of peptide nanotube have been performed by Mi- cro-Raman.14 830 J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 Chen Fig. 1. The AFM image of Human eyebrow. The cuti- cle scale heights can be recorded statistically to differentiate hair origin (reproduced with per- mission of Mr. Yen-fou Chen, and Mr. Hung- min Lin of Taiwan Bruker).
- 4. FORENSIC APPLICATIONS Most of the known forensic applications of nanotech- nology focus on the development and improvement of DNA microchips and array.15 Since little is known about utilizing nanotechnology on other types of evidences, vari- ous forensic applications will be discussed in the following paragraphs. Latent Fingerprint Enhancement of CdS The late Dr. Menzel was the pioneer of the usage of photoluminescent CdS semiconductor nanocrystal capped with dioctyl sulfosuccinate to enhance latent fingerprint detection.16 His concept was to apply nanocrystal fluores- cent dye on articles that have been pre-fumed with cyano- acrylate ester and also on the sticky side of electrical tape without pre-fuming. Nano-Fingerprint Residue Visualization Worley and coworkers at Los Alamos National Lab developed a novel method using micro-X-ray fluorescence (MXRF) to detect images of latent fingerprints.17 Unlike common chemical reagents methods where latent prints are developed via reactions between reagents and amino acid, or fatty acid from the fingerprint, MXRF generates latent fingerprints images by detecting inorganic elements in the prints. It is more advantageous due to the non-destructive nature of the analysis, as well as the stability of the inor- ganic residues. During analysis, fingerprints remain intact and can be used for additional tests, such as elemental anal- ysis for gunshot residue, and prints can still be imaged up to an average of eight months under appropriate evidence storage. The most commonly observed inorganic residues in fingerprints are potassium and chloride ions. Other ele- ments that can be found in latent prints by MXRF include silicon, calcium, aluminum, and so on. However, this method also has one drawback. A sebaceous fingerprint left by one subject was successfully imaged by MXRF, but sebaceous prints left by a different person were undetectable, indicat- ing that print elemental composition may be the person and/or diet dependent, and this technique cannot be applied to all cases Because MXRF actually provides an elemental analysis of the inorganic elements found in fingerprints, substances foreign to the hands may also be visualized in- cluding sweat, lotion, saliva, and sunscreen. For example, lotion and sunscreen can be detected due to residual TiO2 or ZnO nanoparticles, while sweat can be detected due to its inorganic components. Furthermore, MXRF can be used to investigate food consumption by linking elements detected in saliva and food residues found in fingerprints to investi- gate missing children cases. Gold Nanoparticles to Enhance PCR Efficiency Lin and colleagues found that Au nanoparticles can be used to dramatically enhance polymerase chain reaction (PCR) efficiency.18 When 0.7 nM of 13 nm Au nanoparti- cles was added into the PCR reagent they found the reac- tion time is decreased while heating/cooling thermal cycle rates is increased. Their results also showed that the it has been suggested that sensitivity improved 5~10 times in conventional PCR, and more than 10,000 times in real-time PCR. The marked improvements in PCR efficiency is at- tributed to the superb heat transfer property of Au nano- particles, another research groups have also begun to uti- lize nanoparticles to forensic biology related researches. AFM and Questioned Documents Khanmy-Vital’s group in Switzerland first used AFM to examine ink crossing in documents to determine se- quence of pen strokes.19 AFM can study the 3-D surface morphology, which provides essential information for de- termining the sequence of lines made by ball pen ink and ribbon dye. They suggest that AFM images present the same qualitative information as obtained by SEM images. Furthermore, since AFM can be operated under ambient conditions without vacuum and conductive coating of sam- ples, potential damages to the sample during the experi- ment can be avoided. The depth of ink crossing, amplitude and phase images of ink on paper are shown in Figure. 2. The crossing sequence can be clearly determined. AFM and the Time of Death Cai and Chen first reported the application of AFM to resolve one of the most crucial issue in forensic science – the estimation of the time of death.20 The morphological changes of blood cells can be useful for the quantitative as- sessment of the time of death. The deformation of cell and membrane surface of unfixed erythrocytes with time lapse is observed. Fissures and cell shrinkage took place in half a day. More protuberances on erythrocytes began to reveal in 2.5 days. The number of protuberance increases with time, so it can be used as an indication for the estimation of the time of death. Protuberance can come from several sources. One is when hemoglobin in cytoplasm flows outward when dehydration induces the formation of holes in cell mem- Forensic Applications of Nanotechnology J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 831
- 5. branes. The other possible source is the integral membrane proteins, such as band 3 protein, glycophorin A and others. In addition, the cytoskeleton proteins reveal that membrane became thinner due to dehydration. Their results suggest AFM is a new potential tool in forensic medicine (the esti- mation of the time of death), and can also analyze other tis- sues, membranes and biological samples. The authors also investigated the time-dependent surface adhesive force and morphology of red blood cells (RBC), and cellular vis- coelavity vs. distance curve under: 1) controlled, room- temperature (temp: 25 °C, humidity: 76%); 2) uncon- trolled, outdoor-environmental (temp: 21.2–33.7 °C, hu- midity: 38.4–87.3%); and 3) controlled, low-temperature (temp: 4 °C, humidity: 62%) condition by AFM.21 RBC ex- hibits typical biconcave shape on a mica substrate, whereas either the biconcave shape or flattened shape was evident on a glass substrate. The mean volume of RBCs on mica was significantly larger than that of cells on glass, but sur- prisingly, the adhesive property of RBC membrane sur- faces was substrate-independent. Over time, the changes in cell volume and adhesive force of the RBC under con- trolled room-temperature condition were similar to those under the uncontrolled outdoor-environmental condition. Under the controlled low-temperature condition, however, the changes in cell volume occurred mainly due to the col- lapse of RBCs, and the curves of adhesive force showed the dramatic alternations in viscoelasticity of RBC. More researches on various environmental factors such as hu- midity, pH value, temperature, and light are needed to estimate blood age accurately. AFM Force Spectroscopy and Bloodstain Thalhammer’s group reported the age determination of dry bloodstain by AFM force spectroscopy.22 In this pre- liminary study the changes in erythrocytes elasticity on a nanometer scale was analyzed via a two-step procedure. In the first step, an overview image was generated showing the presence of several red blood cells, which could be eas- ily detected by their typical “doughnut-like” appearance. Subsequently, AFM was used to test the elasticity by re- cording force-distance curves. The measurements were performed immediately after drying and after 1.5 h, 30 h and 31 days. The conditions were kept constant at room temperature (20 °C) and 30% humidity. The elasticity pat- tern decreased over time, which is most likely influenced by the alteration of the bloodstain during the drying and co- agulation processes. Once the calibration curve of the elas- ticity over time is developed, the age of bloodstains can be estimated and used to assist in criminal investigations. AFM and Trace Evidence Adya’s group applied AFM to the analyses of textile fibers23 and pressure sensitive adhesives.24 In the fiber study, natural (cotton and wool), and regenerated cellulose (viscose) textile fibers exposed to various environmental stresses for different lengths of times were analyzed by AFM. AFM images were used to quantitatively measure the surface texture parameters of the environmentally stressed fabrics as a function of the exposure time. The fin- est nanoscale details of the surfaces of three weathered fab- rics can be observed and clearly distinguish between the detrimental effects of the imposed environmental condi- tions. Three kinds of fibers were exposed to two different soils (town and riverside) and two different types of water (ponds and water) for zero, two, four and six weeks. The surface morphology of each sample was analyzed for aver- age maximum peak heights (Hpm), average maximum heights (Hz), average maximum valley depths (Hvm), peak -to-valley distances (Rz), the root mean square rough- ness (Rrms) and other parameters to quantify the changes under the different circumstances. This study demonstrated that AFM is a very powerful tool in forensic examination of fiber evidences due to its capability to distinguish between different environmental exposures or forced damages to fi- bers. 832 J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 Chen Fig. 2. (A) The optical micrograph of ink crossing scan area (B) The 3D height image shows the red stamp ink deposits first followed by the blue bullpoint ink deposition (C) The scan area height, Z-sensor, amplitude and phase images (reproduced with permission of Dr. Shuchen Hsieh of National Sun Yat-Sen University).
- 6. Pressure sensitive adhesive (PSA), such as those used in packaging and adhesive tapes, are very often used in criminal activities. Packaging tapes may be used to seal packages containing drugs, explosive devices, or ques- tioned documents, while adhesive and electrical tapes are used to tie up the victims in kidnapping cases. The AFM phase images show dark and bright areas corresponding to the soft polymer molecules and the rough surfactants, re- spectively, on three investigated PSA tapes. The mechani- cal properties of various tapes can be differentiated by the maximum adhesive force of the particles forming the film to the tip (Fmax), the maximum distance of deformation of these particles (dmax), and the adhesion energy (g) of the F-d curves. This is the first study to accurately analyze various tapes by AFM imaging and force mapping. Several studies have also reported other applications of AFM in criminal investigations. One example is a com- putational method that calculates cuticle step height from AFM images for the quantitative assessment of human hair.25 Another example is in the analysis of particle size distribution of powder spray-enhanced the latent finger- print imaging. Figure 3 shows an image with resolution in the nanometer range. Besides the image and surface analysis capabilities of AFM, AFM microcantilever can also be used for selective detection. A review paper by Carrascosa et al.26 discussed many interesting applications of specific target detections performed in the nano and pico levels. Some applications include the analysis of DNA hybridization, detection of two isoforms of prostate specific antigens; C-reactive pro- teins; Salmonella enterica; Vaccinia virus; explosives as trinitrotoluene (TNT), Pentaerythritol Tetranitrate (PETN), and Cyclotrimethylenetrinitramine (RDX). Microcantilever based sensor have become an impor- tant device for detecting low-level molecular interactions with high accuracy. It detects molecules by utilizing the ap- propriate coatings on the cantilever surface. The microcan- tilever sensor detects the target molecule when the mole- cule interacts with the coating molecule. As described in the AFM introduction, any tiny position shift due to molec- ular interaction, recognition, adsorption, or desorption can be observed. When more target molecules accumulate on the cantilever surface, the additional weight caused more bending of the level that leads to more deflection. NANOTOXICOLOGY Nanotechnology has great potential to benefit the so- ciety; however those nanomaterials with unknown novel properties can also cause risks to the environment. The risks from nanomaterials are largely due to their unknown health impacts. After the use of “Magic Nano” spray in Germany, more than 80 people complained of fever, head- ache and difficulty inbreathing, and several went to the hospital due to pulmonary edema. The spray was designed to enhance water and dirt resistance for glass and ceramic tiles. German Federal Institute of Risk Assessment issued a warning against the usage of nanoparticles-containing household products and has resulted in first nanotech-prod- uct withdrawn from German market in 2006. But, direct ev- idence to conclude that all nanomaterials are harmful to the environment and health is limited. Generally, the smaller the nanoparticle the more toxic it is (http://www.oecd.org/ dataoecd/37/19/37770473.pdf and Chemical & Engineer- ing News Vol. 86 No. 35, 1 Sept. 2008, “Study Sizes up Nanomaterial Toxicity”, p. 44) because smaller particle can penetrate more areas in the body. For the same amount of sample, the smaller particles can come in contact with a larger surface area, thus can potentially react with more ac- tive sites. Generally speaking, nanomaterials can enter our body through four entry routes, inhalation, digestion, skin absorption and ingestion. The seriousness of nanotoxicity has been acknowledged and emphasized in a review by the group of Oberdorster.27 They mentioned that after inhala- tion, nanoparticles around the respiratory tract can enter into cells, blood stream, and lymph circulation. Subse- quently, they can penetrate into the bone marrow, lymph nodes, spleen, and heart. Additionally, it has been observed that nanoparticles can cross the blood-brain barrier and Forensic Applications of Nanotechnology J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 833 Fig. 3. AFM image of fingerprint powder spray. (re- produced with permission of Mr. Yen-fou Chen, and Mr. Hung-min Lin of Taiwan Bruker).
- 7. penetrate into the central nervous system and ganglia, caus- ing even more severe damage to the human body. Nanotoxicology is still a new field of research, but the reduction – and eventual removal - of toxicity associated with novel nanomaterials, nanostructures and nanodevices is of paramount importance. FUTURE PROSPECTS With the constant development of nanotechnology, forensic scientists will be encountering various evidences in the nanoscale in the future. When professionals process these nano-evidences, they might raise questions below: How could I process this type of evidence correctly? Will these nano-evidences be toxic to me? How would I protect and my colleagues and myself? Forensic scientists will need to know more information in nanotechnology related fields. Taiwan has great potential and capability to become one of the leading countries in applying nanotechnology to forensic sciences. From the author’s personal experience, the “average” qualification and general knowledge of fo- rensic scientists in Taiwan are better than others in most countries. Therefore, to combine forensic science with nanotechnology and establish world-leading environment is not “mission impossible”. It can be achieved by putting an emphasis on developing educational researches to help provide the skilled workforce and supporting infrastruc- ture/tools needed to advance nanotechnology. This would also require better utilization of forensic lab instrumenta- tions, in conjunction with equipments that can perform nanoscale analysis. Finally, to further develop novel foren- sics and related studies, long-term exchange opportunities with international forensic scientists must be sought to en- sure our awareness of the latest development in forensic science and nanotechnology. Develop education researches, skilled workforce and the supporting infrastructure and tools to advance nanotechnology. Nanotechnology is the future of forensic sciences. REFERENCES 1. (a) Lieber, C. M. Mrs Bulletin 2003, 28(7), 486-491; (b) Alivisatos, P. Nat. Biotechnol. 2004, 22(1), 47-52; (c) Dlott, D. D. Mater. Sci. Technol. 2006, 22(4), 463-473; (d) Lewenstein, B. V. Sci. Commun. 2005, 27(2), 169-174; (e) Hutchings, G. J.; Haruta, M. Appl. Catal., A 2005, 291(1-2), 2-5; (f) Colton, R. J. J. Vac. Sci. Technol., B 2004, 22(4), 1609-1635; (g) Chen, J. R.; Miao, Y. Q.; He, N. Y.; Wu, X. H.; Li, S. J. Biotechnol. Adv. 2004, 22(7), 505-518; (h) Hernandez-Lopez, J. L.; Bauer, R. E.; Chang, W. S.; Glasser, G.; Grebel-Koehler, D.; Klapper, M.; Kreiter, M.; Leclaire, J.; Majoral, J. P.; Mittler, S.; Mullen, K.; Vasilev, K.; Weil, T.; Wu, J.; Zhu, T.; Knoll, W. Mater. Sci. Eng., C 2003, 23(1-2), 267-274; (i) Bastani, B.; Fernandez, D. Thin Solid Films 2002, 420, 472-477; (j) Launois, H. Appl. Surf. Sci. 2000, 164, 1-1; (k) Guetens, G.; Van Cauwenberghe, K.; De Boeck, G.; Maes, R.; Tjaden, U. R.; van der Greef, J.; Highley, M.; van Oosterom, A. T.; de Bruijn, E. A. J. Chromatogr., B: Anal. Technol. Biomed. Life Sci. 2000, 739(1), 139-150. 2. Brettell, T. A.; Butler, J. M.; Saferstein, R., Forensic science. Anal. Chem. 2005, 77(12), 3839-3860. 3. (a) Thomas, K.; Aguar, P.; Kawasaki, H.; Morris, J.; Nakanishi, J.; Savage, N. Toxicol. Sci. 2006, 92(1), 23-32; (b) Trunov, M. A.; Umbrajkar, S. M.; Schoenitz, M.; Mang, J. T.; Dreizin, E. L. J. Phys. Chem. B 2006, 110(26), 13094-13099; (c) Reis, C. P.; Neufeld, R. J.; Vilela, S.; Ribeiro, A. J.; Veiga, F. J. Microencapsulation 2006, 23(3), 245-257; (d) Femoni, C.; Iapalucci, M. C.; Kaswalder, F.; Longoni, G.; Zacchini, S. Coord. Chem. Rev. 2006, 250(11-12), 1580-1604; (e) Yates, E. A.; Terry, C. J.; Rees, C.; Rudd, T. R.; Duchesne, L.; Skidmore, M. A.; Levy, R.; Thanh, N. T. K.; Nichols, R. J.; Clarke, D. T.; Fernig, D. G. Biochem. Soc. Trans. 2006, 34, 427-430; (f) Nozaki, T.; Okazaki, K. Pure Appl. Chem. 2006, 78(6), 1157-1172; (g) Ding, G. Q.; Shen, W. Z.; Zheng, M. J.; Zhou, Z. B. Nano- technology 2006, 17(10), 2590-2594; (h) Chen, J. H.; Lu, G. H. Nanotechnology 2006, 17(12), 2891-2894. 4. (a) Jung, S.; Yoo, J.; Kim, Y.; Kim, K.; Dhungel, S. K.; Yi, J. Mater. Sci. Eng., C 2006, 26(5-7), 813-817; (b) Venugopal, R.; Lin, P. I.; Chen, Y. T. J. Phys. Chem. B 2006, 110(24), 11691-11696; (c) Groneberg, D. A.; Giersig, M.; Welte, T.; Pison, U. Curr. Drug Targets 2006, 7(6), 643-648; (d) Grodzinski, P.; Silver, M.; Molnar, L. K. Expert Rev. Mol. Diagn. 2006, 6(3), 307-318; (e) Pedroso, S.; Guillen, I. A. Comb. Chem. High Throughput Screening 2006, 9(5), 389- 397; (f) Sweet, L.; Strohm, B. Hum. Ecol. Risk Assess. 2006, 12(3), 528-551. 5. (a) Terrado, E.; Redrado, M.; Munoz, E.; Maser, W. K.; Benito, A. M.; Martinez, M. T. Mater. Sci. Eng., C 2006, 26(5-7), 1185-1188; (b) Dicks, A. L. J. Power Sources 2006, 156(2), 128-141 6. (a) Graveland-Bikker, J. F.; de Kruif, C. G. Trends Food Sci. Technol. 2006, 17(5), 196-203; (b) Reches, M.; Gazit, E. Phys. Biol. 2006, 3(1), S10-S19; (c) Matsumura, S.; Uemura, S.; Mihara, H. Mol. Biosyst. 2005, 1(2), 146-148; (d) Kohli, P.; Martin, C. R. Curr. Pharm. Biotechnol. 2005, 6(1), 35-47; (e) Banerjee, I. A.; Yu, L. T.; Matsui, H. Proc. Natl. Acad. Sci. U. S. A. 2003, 100(25), 14678-14682. 7. (a) Leary, S. P.; Liu, C. Y.; Apuzzo, M. L. I. Neurosurgery 2006, 58(6), 1009-1025; (b) Moos, W. H.; Barry, S. Drug Dev. Res. 2006, 67(1), 1-3; (c) Culliton, B. L.; Zerhouni, E. 834 J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 Chen
- 8. Health Affair. 2006, 25(3), W94-W103; (d) Patel, G. M.; Patel, G. C.; Patel, R. B.; Patel, J. K.; Patel, M. J. Drug Tar- geting 2006, 14(2), 63-67. 8. Hamm, G.; Becker, C.; Henry, C. R. Nanotechnology 2006, 17(8), 1943-1947. 9. Ntima, C. A.; Gbaruko, B. C.; Gbaruko, P. N.; Nwabende, S. E. Abstr. Pap. Am. Chem. Soc. 2005, 230, U1555-U1555. 10. (a) Riguidel, M. Lect. Notes. Comput. Sci. 2006, 3939, 83-98; (b) Kohjiya, S. Adv. Mater. Forum III, Pts 1 and 2 2006, 514-516, 353-358; (c) Jeffery, K. G. In Sofsem 2006: Theory and Practice of Computer Science, Proceedings, 32nd Conference on Current Trends in Theory and Practice of Computer Science, Merin, Czech Republic, January 21-27, 2006, Proceedings 2006, Wiedermann, J.; Tel, G.; Pokorný, J.; Bieliková, M.; Štuller, J., Eds.; Springer-Verlag: Berlin, 2006, 3831, pp 49-60. 11. (a) Barnes, C. H. W. Philos. Trans. R. Soc. London, A 2003, 361(1808), 1487-1492; (b) Ng, J.; Abbott, D. Microelectron. J. 2002, 33(1-2), 171-177. 12. (a) Liu, H. K.; Wang, G. X.; Guo, Z. P.; Wang, J. Z.; Konstantinov, K. J. Nanosci. Nanotechnol. 2006, 6(1), 1-15; (b) Vettiger, P.; Binnig, G. Sci. Am. 2003, 288(1), 46-53. 13. (a) Cheng, Y.-A.; Zheng, B.; Chuang, P.-H.; Hsieh, S. Langmuir 2010, 26(11), 8256-8261; (b) Hsieh, C.-W.; Zheng, B.; Hsieh, S. Chem. Commun. 2010, 46(10), 1655; (c) Hsieh, S. J. Nanosci. Nanotechnol. 2008, 8(11), 5839- 5845; (d) Hsieh, S.; Chao, W.-J.; Hsieh, C.-W. J. Colloid In- terface Sci. 2010, 345(2), 524-527; (e) Hsieh, S.; Cheng, Y.; Hsieh, C.; Liu, Y. Mater. Sci. Eng., B 2009, 156(1-3), 18-23. 14. Matsui, H.; Douberly, G. E. Langmuir 2001, 17(25), 7918- 7922. 15. (a) Perlin, M. W.; Szabady, B. Hum. Mutat. 2002, 19(4), 361-373; (b) Heller, M. J. Annu. Rev. Biomed. Eng. 2002, 4, 129-153. 16. Menzel, E. R.; Takatsu, M.; Murdock, R. H.; Bouldin, K.; Cheng, K. H. J. Forensic Sci. 2000, 45(4), 770-773; (b) Menzel, E. R.; Savoy, S. M.; Ulvick, S. J.; Cheng, K. H.; Murdock, R. H. J. Forensic Sci. 2000, 45(3), 545-551. 17. Worley, C. G.; Wiltshire, S. S.; Miller, T. C.; Havrilla, G. J.; Majidi, V. J. Forensic Sci. 2006, 51(1), 57-63. 18. Li, M.; Lin, Y. C.; Wu, C. C.; Liu, H. S. Nucleic Acids Res. 2005, 33(21), e184. 19. Kasas, S.; Khanmy-Vital, A.; Dietler, G. Forensic Sci. Int. 2001, 119(3), 290-298. 20. Chen, Y.; Cai, J. Y. Micron 2006, 3(4), 339-346. 21. Wu, Y.; Hu, Y.; Cai, J.; Ma, S.; Wang, X.; Chen, Y.; Pan, Y. Micron 2009, 40(3), 359-64. 22. Strasser, S.; Zink, A.; Kada, G.; Hinterdorfer, P.; Peschel, O.; Heckl, W. M.; Nerlich, A. G.; Thalhammer, S. Forensic Sci. Int. 2007, 170(1), 8-14. 23. Canetta, E.; Montiel, K.; Adya, A. K. Forensic Sci. Int. 2009, 191(1-3), 6-14. 24. Canetta, E.; Adya, A. K. Forensic Sci. Int. 2011, 210(1-3), 16-25. 25. (a) Gurden, S. P.; Monteiro, V. F.; Longo, E.; Ferreira, M. M. C. J. Microsc. Oxford 2004, 215, 13-23; (b) Smith, J. R. J. J. Microsc. Oxford 1998, 191, 223-228. 26. Carrascosa, L. G.; Moreno, M.; Alvarez, M.; Lechuga, L. M. TrAC, Trends Anal. Chem. 2006, 25(3), 196-206. 27. Oberdorster, G.; Oberdorster, E.; Oberdorster, J. Environ. Health Perspect. 2005, 113(7), 823-839. Forensic Applications of Nanotechnology J. Chin. Chem. Soc., Vol. 58, No. 6, 2011 835