Emerging Cytokine Biosensors with Optical Detection Modalities and Nanomaterial-Enabled Signal Enhancement

Abstract

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.

Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

“…Ultrasensitive methods are proposed to improve sensitivity, selectivity, simplicity and minimize the sample matrix effects together with minimizing the sample volumes. In addition to traditional colorimetric, chemiluminescent and fluorescent detection, the emerging technologies rely on electrochemical, optical [ 143 ], mechanical or surface plasmon resonance [ 144 ] biosensing, reviewed in [ 74 , 142 , 145 , 146 , 147 ]. Developments in nanotechnologies enable construction of microfluidic devices and biochips [ 74 ].…”

“…Due to the large variety of emerging technologies for cytokine biosensing, it is out of the scope of this review to provide global information on all of them. Several reviews have been published in the last 3 years, where the more detailed information on biosensing can be found [ 59 , 74 , 143 , 144 , 145 , 146 ].…”

Polarization-resolved mechanistic investigation of fluorescence signal intensification on zinc oxide nanorod ends

“…The fluorescence panel in Figure 2(A) with all polarizations allowed during excitation and collection clearly shows the characteristic FINE phenomenon we have previously reported. 10,11,15,28,43 The unique behavior of FINE originates from the coupled and waveguided emission from the fluorophores placed on top of the ZnO NR which travels through the NR via the mechanisms of subwavelength waveguiding and surface evanescent wave propagation. 10,11,28 This optical signal is highly intensified and spatially localized at the NR termini, as clearly displayed in the fluorescence intensity graph plotted as a function of the position along the long axis of the NR in the right panel of Figure 2(A).…”

Bioengineering Solutions for Manufacturing Challenges in CAR T Cells

“…Studies on the metabolic requirements of T cell subsets could yield useful monitoring targets, as advanced process control techniques for mammalian cell culture rely on metabolic flux analysis . PAT for T cell culture could include immune biosensors and spectroscopic techniques . Soft sensors could be used to integrate measurements of secreted cytokines and metabolite concentrations with software modeling to estimate other components .…”