Protein biomarkers, especially cytokines, play a pivotal role in the diagnosis and treatment of a wide spectrum of diseases. Therefore, a critical need for advanced cytokine sensors has been rapidly growing and will continue to expand to promote clinical testing, new biomarker development, and disease studies. In particular, sensors employing transduction principles of various optical modalities have emerged as the most common means of detection. In typical cytokine assays which are based on the binding affinities between the analytes of cytokines and their specific antibodies, optical schemes represent the most widely used mechanisms, with some serving as the gold standard against which all existing and new sensors are benchmarked. With recent advancements in nanoscience and nanotechnology, many of the recently emerging technologies for cytokine detection exploit various forms of nanomaterials for improved sensing capabilities. Nanomaterials have been demonstrated to exhibit exceptional optical properties unique to their reduced dimensionality. Novel sensing approaches based on the newly identified properties of nanomaterials have shown drastically improved performances in both the qualitative and quantitative analyses of cytokines. This article brings together the fundamentals in the literature that are central to different optical modalities developed for cytokine detection. Recent advancements in the applications of novel technologies are also discussed in terms of those that enable highly sensitive and multiplexed cytokine quantification spanning a wide dynamic range. For each highlighted optical technique, its current detection capabilities as well as associated challenges are discussed. Lastly, an outlook for nanomaterial-based cytokine sensors is provided from the perspective of optimizing the technologies for sensitivity and multiplexity as well as promoting widespread adaptations of the emerging optical techniques by lowering high thresholds currently present in the new approaches.

Recent bioapplications of one-dimensional (1D) zinc oxide (ZnO) nanomaterials, despite the short development period, have shown promising signs as new sensors and assay platforms offering exquisite biomolecular sensitivity and selectivity. The incorporation of 1D ZnO nanomaterials has proven beneficial to various modes of biodetection owing to their inherent properties. The more widely explored electrochemical and electrical approaches tend to capitalize on the reduced physical dimensionality, yielding a high surface-to-volume ratio, as well as on the electrical properties of ZnO. The newer development of the use of 1D ZnO nanomaterials in fluorescence-based biodetection exploits the innate optical property of their high anisotropy. This review considers stimulating research advances made to identify and understand fundamental properties of 1D ZnO nanomaterials, and examines various biosensing modes utilizing them, while focusing on the unique optical properties of individual and ensembles of 1D ZnO nanomaterials specifically pertaining to their bio-optical applications in simple and complex fluorescence assays.

The rapidly growing field of proteomics and related applied sectors in the life sciences demands convenient methodologies for detecting and measuring the levels of specific proteins as well as for screening and analyzing for interacting protein systems. Materials utilized for such protein detection and measurement platforms should meet particular specifications which include ease-of-mass manufacture, biological stability, chemical functionality, cost effectiveness, and portability. Polymers can satisfy many of these requirements and are often considered as choice materials in various biological detection platforms. Therefore, tremendous research efforts have been made for developing new polymers both in macroscopic and nanoscopic length scales as well as applying existing polymeric materials for protein measurements. In this review article, both conventional and alternative techniques for protein detection are overviewed while focusing on the use of various polymeric materials in different protein sensing technologies. Among many available detection mechanisms, most common approaches such as optical, electrochemical, electrical, mass-sensitive, and magnetic methods are comprehensively discussed in this article. Desired properties of polymers exploited for each type of protein detection approach are summarized. Current challenges associated with the application of polymeric materials are examined in each protein detection category. Difficulties facing both quantitative and qualitative protein measurements are also identified. The latest efforts on the development and evaluation of nanoscale polymeric systems for improved protein detection are also discussed from the standpoint of quantitative and qualitative measurements. Finally, future research directions towards further advancements in the field are considered.

Understanding protein–surface interactions is crucial to solid-state biomedical applications whose functionality is directly correlated with the precise control of the adsorption configuration, surface packing, loading density, and bioactivity of protein molecules. Because of the small dimensions and highly amphiphilic nature of proteins, investigation of protein adsorption performed on nanoscale topology can shed light on subprotein-level interaction preferences. In this study, we examine the adsorption and assembly behavior of a highly elongated protein, fibrinogen, on both chemically uniform (as-is and buffered HF-treated SiO₂/Si, and homopolymers of polystyrene and poly(methyl methacrylate)) and varying (polystyrene-block-poly(methyl methacrylate)) surfaces. By focusing on high-resolution imaging of individual protein molecules whose configurations are influenced by protein–surface rather than protein–protein interactions, fibrinogen conformations characteristic to each surface are identified and statistically analyzed for structural similarities/differences in key protein domains. By exploiting block copolymer nanodomains whose repeat distance is commensurate with the length of the individual protein, we determine that fibrinogen exhibits a more neutral tendency for interaction with both polystyrene and poly(methyl methacrylate) blocks relative to the case of common globular proteins. Factors affecting fibrinogen–polymer interactions are discussed in terms of hydrophobic and electrostatic interactions. In addition, assembly and packing attributes of fibrinogen are determined at different loading conditions. Primary orientations of fibrinogen and its rearrangements with respect to the underlying diblock nanodomains associated with different surface coverage are explained by pertinent protein interaction mechanisms. On the basis of two-dimensional stacking behavior, a protein assembly model is proposed for the formation of an extended fibrinogen network on the diblock copolymer.

In this study, we characterize incident/scattered polarization-specific and NR position-resolved Raman scattering behaviors of individual zinc oxide nanorods (ZnO NRs). We quantify Raman signals from the five key ZnO phonon modes of E_2L, E_2H–2L, A_1T, E_1T, and E_2H, and reveal the NR position-dependent Raman scattering characteristics of the phonon modes per given light–matter interaction geometry. We then present Raman intensity maps and elucidate Raman behaviors consistent and incongruous with Raman selection rules. In particular, we identify an intriguing Raman scattering phenomenon from the forbidden modes, distinctively occurring at the two NR ends. Their unexpectedly strong and localized scattering signals at the NR termini are contrasted by the scattering behaviors from the rest of the NR positions agreeing with the selection predictions. By carrying out control measurements on isotropic ZnO microparticles (MPs), we ascertain that the unique NR position-specific Raman responses observed on ZnO NRs originate from their high shape anisotropy. Owing to the superior optical property coupled with reduced dimensionality and high geometric anisotropy, ZnO NRs have gained much attention recently for use in optoelectronic, photonic, and biosensor technologies. Raman scattering has been increasingly exploited as a noninvasive and sensitive analytical tool to investigate NR properties pertinent to these applications. Hence, our endeavors, explicitly providing the spatially distinct, polarized Raman scattering behaviors from individual ZnO NRs, will be central to the correct interpretation of Raman data of both the individual and ensemble NRs as well as to the accurate correlation of the measurement outcomes to their chemical/physical/optical properties. Our efforts may also promote novel applications for polarized Raman scattering whose optical outputs on the various positions along the ZnO NRs can be selectively modulated.

Significant research accomplishments have been made so far for the development and application of ZnO nanomaterials in enhanced optical biodetection. The unparalleled optical properties of ZnO nanomaterials and their reduced dimensionality have been successfully exploited to push the limits of conventional optical biosensors and optical biodetection platforms for a wide range of bioanalytes. ZnO nanomaterial-enabled advancements in optical biosensors have been demonstrated to improve key sensor performance characteristics such as the limit of detection and dynamic range. In addition, all nanomaterial forms of ZnO, ranging from 0-dimensional (0D) and 1D to 2D nanostructures, have been proven to be useful, ensuring their versatile fabrication into functional biosensors. The employment of ZnO as an essential biosensing element has been assessed not only for ensembles but also for individual nanomaterials, which is advantageous for the realization of high miniaturization and minimal invasiveness in biosensors and biodevices. Moreover, the nanomaterials’ incorporations into biosensors have been shown to be useful and functional for a variety of optical detection modes, such as absorption, colorimetry, fluorescence, near-band-edge emission, deep-level emission, chemiluminescence, surface evanescent wave, whispering gallery mode, lossy-mode resonance, surface plasmon resonance, and surface-enhanced Raman scattering. The detection capabilities of these ZnO nanomaterial-based optical biosensors demonstrated so far are highly encouraging and, in some cases, permit quantitative analyses of ultra-trace level bioanalytes that cannot be measured by other means. Hence, steady research endeavors are expected in this burgeoning field, whose scientific and technological impacts will grow immensely in the future. This review provides a timely and much needed review of the research efforts made in the field of ZnO nanomaterial-based optical biosensors in a comprehensive and systematic manner. The topical discussions in this review are organized by the different modes of optical detection listed above and further grouped by the dimensionality of the ZnO nanostructures used in biosensors. Following an overview of a given optical detection mode, the unique properties of ZnO nanomaterials critical to enhanced biodetection are presented in detail. Subsequently, specific biosensing applications of ZnO nanomaterials are discussed for ~40 different bioanalytes, and the important roles that the ZnO nanomaterials play in bioanalyte detection are also identified.