The design and application of sensors for monitoring biomolecules in clinical samples is a common goal of the sensing research community. Surface plasmon resonance (SPR) and other plasmonic techniques such as localized surface plasmon resonance (LSPR) and imaging SPR are reaching a maturity level sufficient for their application in monitoring biomolecules in clinical samples. In recent years, the first examples for monitoring antibodies, proteins, enzymes, drugs, small molecules, peptides, and nucleic acids in biofluids collected from patients afflicted with a series of medical conditions (Alzheimer's, hepatitis, diabetes, leukemia, and cancers such as prostate and breast cancers, among others) demonstrate the progress of SPR sensing in clinical chemistry. This Perspective reviews the current status of the field, showcasing a series of early successes in the application of SPR for clinical analysis and detailing a series of considerations regarding sensing schemes, exposing issues with analysis in biofluids, and comparing SPR with ELISA, while providing an outlook of the challenges currently associated with plasmonic materials, instrumentation, microfluidics, bioreceptor selection, selection of a clinical market, and validation of a clinical assay for applying SPR sensors to clinical samples. Research opportunities are proposed to further advance the field and transition SPR biosensors from research proof-of-concept stage to actual clinical applications.
Silver has been demonstrated to be a powerful cationization agent in mass spectrometry (MS) for various olefinic species such as cholesterol and fatty acids. This work explores the utility of metallic silver sputtering on tissue sections for high resolution imaging mass spectrometry (IMS) of olefins by laser desorption ionization (LDI). For this purpose, sputtered silver coating thickness was optimized on an assorted selection of mouse and rat tissues including brain, kidney, liver, and testis. For mouse brain tissue section, the thickness was adjusted to 23 ± 2 nm of silver to prevent ion suppression effects associated with a higher cholesterol and lipid content. On all other tissues, a thickness of at 16 ± 2 nm provided the best desorption/ionization efficiency. Characterization of the species by MS/MS showed a wide variety of olefinic compounds allowing the IMS of different lipid classes including cholesterol, arachidonic acid, docosahexaenoic acid, and triacylglyceride 52:3. A range of spatial resolutions for IMS were investigated from 150 μm down to the high resolution cellular range at 5 μm. The applicability of direct on-tissue silver sputtering to LDI-IMS of cholesterol and other olefinic compounds presents a novel approach to improve the amount of information that can be obtained from tissue sections. This IMS strategy is thus of interest for providing new biological insights on the role of cholesterol and other olefins in physiological pathways or disease.
Physical chemistry, materials science, analytical chemistry and engineering greatly contributed to the increasing popularity of bioanalytical and biophysical applications of surface plasmon resonance (SPR) by providing novel materials, surface chemistry, instrumental concepts, and theory to further understand the plasmonic phenomenon and support innovation in SPR. This perspective article portrays the contemporary state of SPR-based techniques and establishes a list of challenges to be overcome for improving bioanalytical and biophysical applications of plasmonics and surface plasmon resonance.
Near-zero fouling monolayers based on binary patterned peptides allow low nanomolar detection of the matrix metalloproteinase-3 (MMP-3) directly in crude bovine serum, without sample pretreatment, secondary antibody detection or signal amplification. The peptide 3-MPA-HHHDD-OH (3-MPA, 3-mercaptopropionic acid) was found optimal compared to other binary patterned peptides based on 3-MPA-A(x)-B(y)-OH, where 0
Since the last decade, nanohole arrays have emerged from an interesting optical phenomenon to the development of applications in photophysical studies, photovoltaics and as a sensing template for chemical and biological analyses. Numerous methodologies have been designed to manufacture nanohole arrays, including the use of focus ion beam milling, soft-imprint lithography, colloidal lithography and, more recently, modified nanosphere lithography (NSL). With NSL or colloidal lithography, the experimental conditions control the density of the nanosphere mask and, thus, the aspect of the nanohole arrays. Low surface coverage of the nanosphere mask produces disordered nanoholes. Ordered nanohole arrays are obtained with a densely packed nanosphere mask in combination with electrochemical deposition of the metal, glancing angle deposition (GLAD) or etching of the nanospheres prior to metal deposition. A review of these methodologies is presented here with an emphasis on the optical properties of nanoholes interesting in analytical chemistry. In particular, applications of these novel plasmonic materials will be demonstrated as substrates for a localized surface plasmon resonance (LSPR), Surface Plasmon Resonance (SPR), surface enhanced Raman spectroscopy (SERS), and in electrochemistry with nano-patterned electrodes.
CD36 transmembrane proteins have diverse roles in lipid uptake, cell adhesion and pathogen sensing. Despite numerous in vitro studies, how they act in native cellular contexts is poorly understood. A Drosophila CD36 homologue, sensory neuron membrane protein 1 (SNMP1), was previously shown to facilitate detection of lipid-derived pheromones by their cognate receptors in olfactory cilia. Here we investigate how SNMP1 functions in vivo. Structure–activity dissection demonstrates that SNMP1's ectodomain is essential, but intracellular and transmembrane domains dispensable, for cilia localization and pheromone-evoked responses. SNMP1 can be substituted by mammalian CD36, whose ectodomain can interact with insect pheromones. Homology modelling, using the mammalian LIMP-2 structure as template, reveals a putative tunnel in the SNMP1 ectodomain that is sufficiently large to accommodate pheromone molecules. Amino-acid substitutions predicted to block this tunnel diminish pheromone sensitivity. We propose a model in which SNMP1 funnels hydrophobic pheromones from the extracellular fluid to integral membrane receptors.
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