Christy L. Haynes

Surface-enhanced: Raman spectroscopy

New substrates and single-molecule detection are just two of the advances that are fueling interest in SERS.

Cytotoxicity of Graphene Oxide and Graphene in Human Erythrocytes and Skin Fibroblasts

Two-dimensional carbon-based nanomaterials, including graphene oxide and graphene, are potential candidates for biomedical applications such as sensors, cell labeling, bacterial inhibition, and drug delivery. Herein, we explore the biocompatibility of graphene-related materials with controlled physical and chemical properties. The size and extent of exfoliation of graphene oxide sheets was varied by sonication intensity and time. Graphene sheets were obtained from graphene oxide by a simple (hydrazine-free) hydrothermal route. The particle size, morphology, exfoliation extent, oxygen content, and surface charge of graphene oxide and graphene were characterized by wide-angle powder X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, and zeta-potential. One method of toxicity assessment was based on measurement of the efflux of hemoglobin from suspended red blood cells. At the smallest size, graphene oxide showed the greatest hemolytic activity, whereas aggregated graphene sheets exhibited the lowest hemolytic activity. Coating graphene oxide with chitosan nearly eliminated hemolytic activity. Together, these results demonstrate that particle size, particulate state, and oxygen content/surface charge of graphene have a strong impact on biological/toxicological responses to red blood cells. In addition, the cytotoxicity of graphene oxide and graphene sheets was investigated by measuring mitochondrial activity in adherent human skin fibroblasts using two assays. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, a typical nanotoxicity assay, fails to predict the toxicity of graphene oxide and graphene toxicity because of the spontaneous reduction of MTT by graphene and graphene oxide, resulting in a false positive signal. However, appropriate alternate assessments, using the water-soluble tetrazolium salt (WST-8), trypan blue exclusion, and reactive oxygen species assay reveal that the compacted graphene sheets are more damaging to mammalian fibroblasts than the less densely packed graphene oxide. Clearly, the toxicity of graphene and graphene oxide depends on the exposure environment (i.e., whether or not aggregation occurs) and mode of interaction with cells (i.e., suspension versus adherent cell types).

Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity

This paper uses the measure of hemolysis to evaluate the toxicity of nonporous and porous silica nanoparticles with varied sizes and investigates the effects of porous structure and integrity on the nanoparticle-cell interaction. The results show that both nonporous and porous silica cause red blood cell membrane damage in a concentration- and size-dependent manner. In the case of mesoporous silica nanoparticles, the size-dependent hemolysis effect is only present when the nanoparticles have long-range ordered porous structure, revealing that pore structure is critical in cell-nanoparticle interactions. Mesoporous silica nanoparticles show lower hemolytic activity than their nonporous counterparts of similar size, likely due to fewer silanol groups on the cell-contactable surface of the porous silica nanoparticles. The extent of hemolysis by mesoporous silica nanoparticles increases as the pore structure is compromised by mild aging in phosphate-buffered solutions, initiating mesopore collapse. The pore integrity of mesoporous silica nanoparticles is examined by TEM, XRD, N(2) adsorption-desorption isotherms, and quantification of dissolved silica. In these nanoparticles, pore stability is clearly an important factor in determining the hemolytic activity; further work demonstrates that nanoparticle-induced hemolysis can be eliminated by modifying the silanol surface with a poly(ethylene glycol) coating.

The big picture on nanomedicine: the state of investigational and approved nanomedicine products

UNLABELLED Developments in nanomedicine are expected to provide solutions to many of modern medicines unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study identifies several interesting trends forecasting the future of nanomedicine. FROM THE CLINICAL EDITOR In this one of a kind review, the state of nanomedicine commercialization is discussed, concentrating only on nanomedicine-based developments and products that are either in clinical trials or have already been approved for use.

Recent progress in SERS biosensing

This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing.

Analytical methods to assess nanoparticle toxicity

During the past 20 years, improvements in nanoscale materials synthesis and characterization have given scientists great control over the fabrication of materials with features between 1 and 100 nm, unlocking many unique size-dependent properties and, thus, promising many new and/or improved technologies. Recent years have found the integration of such materials into commercial goods; a current estimate suggests there are over 800 nanoparticle-containing consumer products (The Project on Emerging Nanotechnologies Consumer Products Inventory, , accessed Oct. 2008), accounting for 147 billion USD in products in 2007 (Nanomaterials state of the market Q3 2008: stealth success, broad impact, Lux Research Inc., New York, NY, 2008). Despite this increase in the prevalence of engineered nanomaterials, there is little known about their potential impacts on environmental health and safety. The field of nanotoxicology has formed in response to this lack of information and resulted in a flurry of research studies. Nanotoxicology relies on many analytical methods for the characterization of nanomaterials as well as their impacts on in vitro and in vivo function. This review provides a critical overview of these techniques from the perspective of an analytical chemist, and is intended to be used as a reference for scientists interested in conducting nanotoxicological research as well as those interested in nanotoxicological assay development.

Vertically Oriented Sub-10-nm Plasmonic Nanogap Arrays

Nanometric gaps in noble metals can harness surface plasmons, collective excitations of the conduction electrons, for extreme subwavelength localization of electromagnetic energy. Positioning molecules within such metallic nanogaps dramatically enhances light-matter interactions, increasing absorption, emission, and, most notably, surface-enhanced Raman scattering (SERS). However, the lack of reproducible high-throughput fabrication techniques with nanometric control over the gap size has limited practical applications. Here we show sub-10-nm metallic nanogap arrays with precise control of the gaps size, position, shape, and orientation. The vertically oriented plasmonic nanogaps are formed between two metal structures by a sacrificial layer of ultrathin alumina grown using atomic layer deposition. We show increasing local SERS enhancements of up to 10(9) as the nanogap size decreases to 5 nm. Because these sub-10-nm gaps can be fabricated at high densities using conventional optical lithography over an entire wafer, these results will have significant implications for spectroscopy and nanophotonics.

Towards advanced chemical and biological nanosensors - An overview

This paper reviews recent developments in the design and application of two types of optical nanosensor, those based on: (1) localized surface plasmon resonance (LSPR) spectroscopy and (2) surface-enhanced Raman scattering (SERS). The performance of these sensors is discussed in the context of biological and chemical sensing. The first section addresses the LSPR sensors. Arrays of nanotriangles were evaluated and characterized using realistic protein/ligand interactions. Isolated, single nanoparticles were used for chemosensing and performed comparably to the nanoparticle array sensors. In particular, we highlight the effect of nanoparticle morphology on sensing response. The second section details the use of SERS sensors using metal film over nanosphere (MFON) surfaces. The high SERS enhancements and long-term stability of MFONs were exploited in order to develop SERS-based sensors for two important target molecules: a Bacillus anthracis biomarker and glucose in a serum protein mixture.

Toxicity of Engineered Nanoparticles in the Environment

While nanoparticles occur naturally in the environment and have been intentionally used for centuries, the production and use of engineered nanoparticles has seen a recent spike, which makes environmental release almost certain. Therefore, recent efforts to characterize the toxicity of engineered nanoparticles have focused on the environmental implications, including exploration of toxicity to organisms from wide-ranging parts of the ecosystem food webs. Herein, we summarize the current understanding of toxicity of engineered nanoparticles to representatives of various trophic levels, including bacteria, plants, and multicellular aquatic/terrestrial organisms, to highlight important challenges within the field of econanotoxicity, challenges that analytical chemists are expertly poised to address.

Assessing Nanoparticle Toxicity

Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.