ACS Measurement Science Au最新文献

This article provides an overview of the work reported in the past decade in the field of microfluidic fuel cells. To develop appropriate research, the most commonly used electrocatalytic materials were considered and a new classification was proposed based on their nature: abiotic, hybrid, or biological. This classification allowed the authors to discern the information collected. In this sense, the types of electrocatalysts used for the oxidation of the most common fuels in different environments, such as glucose, ethanol, methanol, glycerol, and lactate, were presented. There are several phenomena presented in this article. This information gives an overview of where research is heading in the field of materials for electrocatalysis, regardless of the fuel used in the microfluidic fuel cell: the synthesis of abiotic and biological materials to obtain hybrid materials that allow the use of the best properties of each material.

With the definition of therapeutics now encompassing transplanted or engineered cells and their molecular products, there is a growing scientific necessity for analytics to understand this new category of drugs. This Perspective highlights the recent development of new measurement science on label-free single cell analysis, nanosensor chemical cytometry (NCC), and their potential for cellular therapeutics and precision medicine. NCC is based on microfluidics integrated with fluorescent nanosensor arrays utilizing the optical lensing effect of a single cell to real-time extract molecular properties and correlate them with physical attributes of single cells. This new class of cytometry can quantify the heterogeneity of the multivariate physicochemical attributes of the cell populations in a completely label-free and nondestructive way and, thus, suggest the vein-to-vein conditions for the safe therapeutic applications. After the introduction of the NCC technology, we suggest the technological development roadmap for the maturation of the new field: from the sensor/chip design perspective to the system/software development level based on hardware automation and deep learning data analytics. The advancement of this new single cell sensing technology is anticipated to aid rich and multivariate single cell data setting and support safe and reliable cellular therapeutics. This new measurement science can lead to data-driven personalized precision medicine.

Surface enhanced Raman scattering (SERS), since its discovery in the mid-1970s, has taken on many roles in the world of analytical measurement science. From identifying known and unknown chemicals in mixtures such as pharmaceutical and environmental samples to enabling qualitative and quantitative analysis of biomolecules and biomedical disease markers (or biomarkers), furthermore expanding to tracking nanostructures in vivo for medical diagnosis and therapy. This is because SERS combines the inherent power of Raman scattering capable of molecular species identification, topped with tremendous amplification in the Raman signal intensity when the molecule of interest is positioned near plasmonic nanostructures. The higher the SERS signal amplification, the lower the limit of detection (LOD) that could be achieved for the above applications. Therefore, improving SERS sensing efficiencies is vital. The signal reproducibility and SERS enhancement factor (EF) heavily rely on plasmonic nanostructure design, which has led to tremendous work in the field. But SERS signal and EF reproducibility remain key limitations for its wider market usability. This Review will scrutinize factors, some recognized and some often overlooked, that dictate the SERS signal and are of utmost importance to enable reproducible SERS EFs. Most of the factors pertain to colloidal labeled SERS. Some critically reviewed factors include the nanostructure’s surface area as a limiting factor, SERS hot-spots including optimizing the SERS EF within the hot-spot volume and positioning labels, properties of label molecules governing molecule orientation in hot-spots, and resonance effects. A better understanding of these factors will enable improved optimization and control of the experimental SERS, enabling extremely sensitive LODs without overestimating the SERS EFs. These are crucial steps toward identification and reproducible quantification in SERS sensing.

The critical performance factors such as selectivity, sensitivity, operational and storage stability, and response time of electrochemical biosensors are governed mainly by the function of their key component, the bioelectrode. Suitable design and fabrication strategies of the bioelectrode interface are essential for realizing the requisite performance of the biosensors for their practical utility. A multifaceted attempt to achieve this goal is visible from the vast literature exploring effective strategies for preparing, immobilizing, and stabilizing biorecognition elements on the electrode surface and efficient transduction of biochemical signals into electrical ones (i.e., current, voltage, and impedance) through the bioelectrode interface with the aid of advanced materials and techniques. The commercial success of biosensors in modern society is also increasingly influenced by their size (and hence portability), multiplexing capability, and coupling in the interface of the wireless communication technology, which facilitates quick data transfer and linked decision-making processes in real-time in different areas such as healthcare, agriculture, food, and environmental applications. Therefore, fabrication of the bioelectrode involves careful selection and control of several parameters, including biorecognition elements, electrode materials, shape and size of the electrode, detection principles, and various fabrication strategies, including microscale and printing technologies. This review discusses recent trends in bioelectrode designs and fabrications for developing electrochemical biosensors. The discussions have been delineated into the types of biorecognition elements and their immobilization strategies, signal transduction approaches, commonly used advanced materials for electrode fabrication and techniques for fabricating the bioelectrodes, and device integration with modern electronic communication technology for developing electrochemical biosensors of commercial interest.

By utilizing a high-temperature superconducting quantum interference device (high-T_c SQUID) magnetometer, an alternating current (AC) magnetosusceptometer, referred to as an analyzer, was developed for ultrasensitive immunoassays. The analyzer has been applied to assay biomarkers in human plasma associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). The involved assay methodology is the so-called immunomagnetic reduction (IMR). Such an analyzer has been approved for clinical use in Taiwan and Europe. The mass production of the analyzer is needed for clinical utilities. The issue of exploring analyzer-to-analyzer variations in the performances becomes critical. Unfortunately, there is no standard characterization to determine the variations in performances among analyzers. In this study, key characterizations, such as output signal stability, signal-to-noise ratio, measured concentrations of a control sample, etc., are proposed. In total, three analyzers are characterized in this work. The detected biomarkers include amyloid peptides, total tau protein, phosphorylated tau protein, and α-synuclein protein for AD and PD. Through one-way ANOVA for any of the characterizations among the three analyzers, it was found that there was no significant difference in any of these characterizations among the analyzers (p > 0.05). Furthermore, the three analyzers are applied to assay biomolecules for AD and PD in reference samples. High correlations (r > 0.8) in measured concentrations of any of these biomarkers in reference samples were obtained among the three analyzers. The results demonstrate that the proposed characterizations are feasible for achieving consistent performance among high-T_c SQUID-based AC magnetosusceptometers for assaying biomolecules.

Multiplexed molecular profiling of tissue microenvironments, or spatial omics, can provide critical insights into cellular functions and disease pathology. The coupling of laser microdissection with mass spectrometry-based proteomics has enabled deep and unbiased mapping of >1000 proteins. However, the throughput of laser microdissection is often limited due to tedious two-step procedures, sequential laser cutting, and sample collection. The two-step procedure also hinders the further improvement of spatial resolution to <10 μm as needed for subcellular proteomics. Herein, we developed a high-throughput and high-resolution spatial proteomics platform by seamlessly coupling deep ultraviolet (DUV) laser ablation (LA) with nanoPOTS (Nanodroplet Processing in One pot for Trace Samples)-based sample preparation. We demonstrated the DUV-LA system can quickly isolate and collect tissue samples at a throughput of ∼30 spots/min and a spatial resolution down to 2 μm from a 10 μm thick human pancreas tissue section. To improve sample recovery, we developed a proximity aerosol collection approach by placing DMSO droplets close to LA spots. We demonstrated the DUV-LA-nanoPOTS platform can detect an average of 1312, 1533, and 1966 proteins from ablation spots with diameters of 7, 13, and 19 μm, respectively. In a proof-of-concept study, we isolated and profiled two distinct subcellular regions of the pancreas tissue revealed by hematoxylin and eosin (H&E) staining. Quantitative proteomics revealed proteins specifically enriched to subcellular compartments.

Bioluminescence emitted from a luciferase-catalyzed oxidation of luciferin has been broadly utilized to report on biological events, predominantly through relative changes in the light output. Recent advances in protein engineering and synthetic chemistry have yielded bioluminescent systems with markedly improved brightness and bioavailability. These developments have enabled not only the detection of biological events at far lower expression levels but also new opportunities utilizing bioluminescence to power photochemistry in cells. Regardless of the application, bioluminescence analyses have leaned heavily on the use of luminometers to measure the light output of a system. Current luminometers report the light output of a sample in relative units, limiting the ability to compare data between instruments and preventing the absolute power of a bioluminescent system from being quantified. Luminescent solution calibrants comprising luciferases and their cognate luciferins that have been characterized for absolute light output would enable calibration of any given luminometer for absolute photon counting. To this end, we have built a custom light detection apparatus and used it alongside wavelength-matched LED light sources emitting at 450 and 561 nm to characterize the absolute power of a series of NanoLuc and firefly luciferase solutions, respectively. This approach revealed that these two common luciferases produce 3.72 × 10^–18 and 7.25 × 10^–20 watts/molecule, respectively. Components of these luminescent solution calibrants are commercially available and produce stable bioluminescent signals over 2–5 min, enabling any luminometer to be calibrated for power measurements of bioluminescence emitted by these two luciferases in units of watts or photons per second.

In this study, we demonstrate the combination of a tunable broadband mid-infrared (MIR) femtosecond laser source separately coupled to a ZnSe crystal horizontal attenuated total reflection (ATR) sensor cell for liquid phase samples and to a substrate-integrated hollow waveguide (iHWG) for gas phase samples. Utilizing this emerging light source technology as an alternative MIR radiation source for Fourier transform infrared (FTIR) spectroscopy opens interesting opportunities for analytical applications. In a first approach, we demonstrate the quantitative analysis of three individual samples, ethanol (liquid), methane (gas), and 2-methyl-1-propene (gas), with limits of detection of 0.3% (ethanol) and 22 ppm_v and 74 ppm_v (methane and isobutylene), respectively, determined at selected emission wavelengths of the MIR laser source (i.e., 890 cm^–1, 1046 and 1305 cm^–1). Hence, the applicability of a broadband MIR femtosecond laser source as a bright alternative light source for quantitative analysis via FTIR spectroscopy in various sensing configurations has been demonstrated.

Cell-based assays enable molecular-level studies of cellular responses to drug candidates or potential toxins. Transactivation assays quantify the activation or inhibition of nuclear receptors, key transcriptional regulators of gene targets in mamalian cells. One such assay couples the expression of luciferase to the transcriptional activity of estrogen receptor-alpha (ERα). While this assay is regularly used to screen for agonists and antagonists of the estrogen signaling pathway, the setup relies on monolayer cultures in which cells are plated directly onto the surface of cell-compatible plasticware. The tumor microenvironment is more than a collection of cancerous cells and is profoundly influenced by tissue architecture, the presence of extracellular matrices, and intercellular signaling molecules produced by non-cancerous neighboring cells (e.g., fibroblasts). There exists a need for three-dimensional culture platforms that can be rapidly prototyped to assess new configurations and readily produced in the large numbers needed for translational studies and screening applications. Here, we demonstrate the utility of the paper-based culture platform to probe the effects of intercellular signaling between two cell types. We used paper scaffolds to generate tumor-like environments, forming a defined volume of breast cancer cells suspended in collagen. By placing the paper scaffolds in commercial 96-well plates, we compared monocultures of only breast cancer cells with coculture configurations containing fibroblasts in different locations that mimicked the stages of breast cancer progression. We show that ERα transactivation in the T47D-KBluc cell line is affected by the presence, number, and proximity of fibroblasts, and is a consequence of intercellular signaling molecules. After screening a small library of fibroblast-secreted signaling molecules, we showed that interleukin-6 (IL-6) was the primary driver of reduced estradiol sensitivity. These effects were mitigated in the coculture configurations by the addition of an IL-6 neutralizing antibody. We also assessed estrogen receptor expression and transcriptional regulation, further demonstrating the utility of the paper-based platform for detailed mechanistic studies.

Numerous transformation products are formed indoors, but they are outside the scope of current chemical databases. In this study, an in silico spectral database was established to screen previously unknown indoor transformation products of organophosphorus compounds (OPCs). An R package was developed that incorporated four indoor reactions to predict the transformation products of 712 seed OPCs. By further predicting MS² fragments, an in silico spectral database was established consisting of 3509 OPCs and 28,812 MS² fragments. With this database, 40 OPCs were tentatively detected in 23 indoor dust samples. This is the greatest number of OPCs reported to date indoors, among which two novel phosphonates were validated using standards. Twenty-four of the detected OPCs were predicted transformation products in which oxidation from organophosphites plays a major role. To confirm this, the in silico spectral database was expanded to include organophosphites for suspect screening in five types of preproduction plastics. A broad spectrum of 14 organophosphites was detected, with a particularly high abundance in polyvinyl chloride plastics and indoor end-user goods. This demonstrated the significant contribution of organophosphites to indoor organophosphates via oxidation, highlighting the strength of in silico spectral databases for the screening of unknown indoor transformation products.