Annual Review of Analytical Chemistry - Volume 1, 2008

The ability to control the size, shape, and material of a surface has reinvigorated the field of surface-enhanced Raman spectroscopy (SERS). Because excitation of the localized surface plasmon resonance of a nanostructured surface or nanoparticle lies at the heart of SERS, the ability to reliably control the surface characteristics has taken SERS from an interesting surface phenomenon to a rapidly developing analytical tool. This article first explains many fundamental features of SERS and then describes the use of nanosphere lithography for the fabrication of highly reproducible and robust SERS substrates. In particular, we review metal film over nanosphere surfaces as excellent candidates for several experiments that were once impossible with more primitive SERS substrates (e.g., metal island films). The article also describes progress in applying SERS to the detection of chemical warfare agents and several biological molecules.

Monitoring changes in chemical concentrations over time in complex environments is typically performed using sensors and spectroscopic techniques. Another approach is to couple sampling methods, such as microdialysis, with chromatographic, electrophoretic, or enzymatic assays. Recent advances of such coupling have enabled improvements in temporal resolution, multianalyte capability, and automation. In a sampling and analysis method, the temporal resolution is set by the mass sensitivity of the analytical method, analysis time, and zone dispersion during sampling. Coupling methods with high speed and mass sensitivity to microdialysis sampling help to reduce some of these contributions to yield methods with temporal resolution of seconds. These advances have been primarily used in monitoring neurotransmitters in vivo. This review covers the problems associated with chemical monitoring in the brain, recent advances in using microdialysis for time-resolved in vivo measurements, sample applications, and other potential applications of the technology such as determining reaction kinetics and process monitoring.

Optical measurement techniques are powerful tools for the detailed study of combustion chemistry and physics. Although traditional combustion diagnostics based on continuous-wave and nanosecond-pulsed lasers continue to dominate fundamental combustion studies and applications in reacting flows, revolutionary advances in the science and engineering of ultrafast (picosecond- and femtosecond-pulsed) lasers are driving the enhancement of existing diagnostic techniques and enabling the development of new measurement approaches. The ultrashort pulses afforded by these new laser systems provide unprecedented temporal resolution for studies of chemical kinetics and dynamics, freedom from collisional-quenching effects, and tremendous peak powers for broad spectral coverage and nonlinear signal generation. The high pulse-repetition rates of ultrafast oscillators and amplifiers allow previously unachievable data-acquisition bandwidths for the study of turbulence and combustion instabilities. We review applications of ultrafast lasers for optical measurements in combusting flows and sprays, emphasizing recent achievements and future opportunities.

Mass spectrometry (MS) is an excellent technology for molecular imaging because of its high data dimensionality. MS can monitor thousands of individual molecular data channels measured as mass-to-charge (m/z). We describe the use of matrix-assisted laser desorption/ionization (MALDI) MS for the image analysis of proteins, peptides, lipids, drugs, and metabolites in tissues. We discuss the basic instrumentation and sample preparation methods needed to produce high-resolution images and high image reproducibility. Matrix-addition protocols are briefly discussed along with normal operating procedures, and selected biological and medical applications of MALDI imaging MS are described. We give examples of both two- and three-dimensional imaging, including normal mouse embryo implantation, sperm maturation in mouse epididymis, protein distributions in brain sections, protein alterations as a result of drug administration, and protein changes in brain due to neurodegeneration and tumor formation. Advantages of this technology and future challenges for its improvement are discussed.

Organic-semiconductor interfaces are playing increasingly important roles in fields ranging from electronics to nanotechnology to biosensing. The continuing decrease in microelectronic device feature sizes is raising an especially great interest in understanding how to integrate molecular systems with conventional, inorganic microelectronic materials, particularly silicon. The explosion of interest in the biological sciences has provided further impetus for learning how to integrate biological molecules and systems with microelectronics to form true bioelectronic systems. Organic monolayers present an excellent opportunity for surmounting many of the practical barriers that have hindered the full integration of microelectronics technology with organic and biological systems. Of all the semiconductor materials, silicon and diamond stand out as unique. This review focuses upon the preparation and characterization of organic and biomolecular layers on semiconductor surfaces, with special emphasis on monolayers formed on silicon and diamond.

There are thousands of different nanometer-scale pores in biology, many of which act as sensors for specific chemical agents. Recent work suggests that protein and solid-state nanopores have many potential uses in a wide variety of analytical applications. In this review we survey this field of research and discuss the prospects for advances that could be made in the near future.

Biochip arrays have enabled the massively parallel analysis of genomic DNA and hold great promise for application to the analysis of proteins, carbohydrates, and small molecules. Surface chemistry plays an intrinsic role in the preparation and analysis of biochips by providing functional groups for immobilization of ligands, providing an environment that maintains activity of the immobilized molecules, controlling nonspecific interactions of analytes with the surface, and enabling detection methods. This review describes recent advances in surface chemistry that enable quantitative assays of a broad range of biochemical activities. The discussion emphasizes the use of self-assembled monolayers of alkanethiolates on gold as a structurally well-defined and synthetically flexible platform for controlling the immobilization and activity of molecules in an array. The review also surveys recent methods of performing label-free assays, and emphasizes the use of matrix-assisted laser desorption/ionization mass spectrometry to directly observe molecules attached to the self-assembled monolayers.

Liposomes are structurally and functionally some of the most versatile supramolecular assemblies in existence. Since the beginning of active research on lipid vesicles in 1965, the field has progressed enormously and applications are well established in several areas, such as drug and gene delivery. In the analytical sciences, liposomes serve a dual purpose: Either they are analytes, typically in quality-assessment procedures of liposome preparations, or they are functional components in a variety of new analytical systems. Liposome immunoassays, for example, benefit greatly from the amplification provided by encapsulated markers, and nanotube-interconnected liposome networks have emerged as ultrasmall-scale analytical devices. This review provides information about new developments in some of the most actively researched liposome-related topics.

The separation of proteins in biology samples has long been recognized as an important and daunting endeavor that continues to have enormous impact on human health. Today's technology for protein separations has its origins in the early nanotechnology of the 1950s and 1960s, and the methods include immunoassays and other affinity extractions, electrophoresis, and chromatography. What is different today is the need to resolve and identify many low-abundance proteins within complex biological matrices. Multidimensional separations are the rule, high speed is needed, and the separations must be able to work with mass spectrometry for protein identification. Hybrid approaches that combine disparate separation tools (including recognition, electrophoresis, and chromatography) take advantage of the fact that no single class of separation can resolve the proteins in a biological matrix. Protein separations represent a developing area technologically, and understanding the principles of protein separations from a molecular and nanoscale viewpoint will enable today's researchers to invent tomorrow's technology.

Invented as a surface analytical technique capable of imaging individual atoms and molecules in real space, scanning tunneling microscopy (STM) has developed and advanced into a technique able to measure a variety of structural, functional, and spectroscopic properties and relationships at the single-molecule level. Here, we review basic STM operation and image interpretation, techniques developed to manipulate single atoms and molecules with the STM to measure functional properties of surfaces, local spectroscopies used to characterize atoms and molecules at the single-molecule level, and surface perturbations affecting surface coverage and surface reactions. Each section focuses on determining the identity and function of chemical species so as to elucidate information beyond topography with STM.

Coherent anti-Stokes Raman scattering (CARS) microscopy is a label-free imaging technique that is capable of real-time, nonperturbative examination of living cells and organisms based on molecular vibrational spectroscopy. Recent advances in detection schemes, understanding of contrast mechanisms, and developments of laser sources have enabled superb sensitivity and high time resolution. Emerging applications, such as metabolite and drug imaging and tumor identification, raise many exciting new possibilities for biology and medicine.