Vascular stenosis caused by atherosclerosis can lead to platelet activation and aggregation in thrombosis. However, the efficacy of antiplatelet drugs under stenosis is not well understood due to the lack of analytical tools. Here we demonstrate a new method combining optofluidic time-stretch quantitative phase microscopy and a 3D stenosis chip to enable highspeed, high-resolution, label-free imaging of circulating platelet aggregates under atherogenic flow conditions. Interestingly, our findings indicate that the proposed high-speed on-chip optofluidic imaging is a powerful tool for studying platelet biology, antiplatelet drug screening, and developing therapeutic strategies for patients with atherosclerotic diseases.
There is widespread concern about the safety of COVID-19 vaccinations related to platelet hyperactivity. However, their long-term influence on platelet activity remains unknown. We address this issue by applying a high-speed bright-field microscope based on optical frequency-division multiplexing and microfluidics for massive image-based analysis. We performed image-based single-cell profiling and temporal monitoring of circulating platelet aggregates in the blood samples of healthy human participants before and after they received three vaccination doses over a nearly one-year period. The results demonstrate no significant or persistent change in platelet activity after vaccine doses.
KEYWORDS: Surface enhanced Raman spectroscopy, Chemical fiber sensors, Biological and chemical sensing, Sensors, In situ remote sensing, Chemical analysis, Biosensing, Stretchable circuits, Sensor technology, Nanolithography
Wearable sensor technology is a powerful tool, but conventional wearable sensors cannot perform simultaneous chemical sensing of multiple biomarkers in biofluids such as sweat and saliva because they are typically sensitive to only one type of chemical in an analyte at a time. Here we present a wearable dual-surface substrate for in situ surface-enhanced Raman spectroscopy (SERS). The substrate is composed of a gold nanomesh structure that can be tailored into any shape and attached to virtually any surface. Notedly, SERS can be performed on both surfaces of the substrate, highly effective for multiplexed in situ chemical sensing of biofluids.
Raman optical activity (ROA) is a powerful tool for identifying the absolute conformational information and behavior of chiral molecules in aqueous solutions, but suffers from low sensitivity. Here we report our development of a silicon nanodisk array that tailors a chiral field to significantly increase the interaction between the excitation light and chiral molecules via exploiting a dark mode. Specifically, we used the array with pairs of chemical and biological enantiomers to show >100x enhanced chiral light-molecule interaction with negligible artifacts for ROA measurements. Our silicon nanodisk array opens a cost-effective way for conformational analysis of trace chiral molecules.
Surface-enhanced Raman spectroscopy (SERS) is a powerful tool for vibrational spectroscopy, but is compromised by its low reproducibility, uniformity, biocompatibility, and durability. This is because it depends on “hot spots” for high signal enhancement. Here we report our experimental demonstration of a plasmon-free nanostructure composed of a two-dimensional array of porous carbon nanowires as a SERS substrate for highly sensitive, biocompatible, and reproducible SERS. Specifically, the substrate provides not only high signal enhancement, but also high reproducibility and fluorescence quenching capability. We experimentally demonstrated these excellent properties with various molecules such as rhodamine 6G (R6G), β-lactoglobulin, and glucose.
Vascular stenosis is a pathological hallmark of atherosclerosis, but its transient process is not well understood due to the lack of analytical tools to study it. Here we report spatiotemporally resolved observation of shear-induced platelet aggregation by combining a microfluidic on-chip stenosis model and optofluidic time-stretch microscopy. Our results indicate a synergistic effect of stenosis and agonists on platelet activation and aggregation. Particularly, an agonist, thrombin receptor activator peptide 6, causes preferential enhancement of platelet aggregation. Our findings are expected to deepen our understanding of stenosis-induced platelet aggregation and pave ways for developing effective antithrombotic therapeutics.
In COVID-19 therapy with artificial lungs such as extracorporeal membrane oxygenation (ECMO) machines, platelets in the extracorporeal circulation are often activated by their contact with the artificial materials, leading to the formation of blood clots followed by serious complications such as stroke and heart attack. However, anticoagulation and antithrombotic management is challenging due to the lack of testing tools to evaluate the circulation. Here we demonstrate real-time monitoring of thrombogenesis in the circulation of an ECMO-equipped goat with an intelligent platelet aggregate characterizer (iPAC), which is based on imaging flow cytometry and deep-learning-based analysis of numerous platelet aggregates in blood.
In the near future, single-molecule surface-enhanced Raman spectroscopy (SERS) is expected to expand the family of popular analytical tools for single-molecule characterization. We provide a roadmap for achieving single molecule SERS through different enhancement strategies for diverse applications. We introduce some characteristic features related to single-molecule SERS, such as Raman enhancement factor, intensity fluctuation, and data analysis. We then review recent strategies for enhancing the Raman signal intensities of single molecules, including electromagnetic enhancement, chemical enhancement, and resonance enhancement strategies. To demonstrate the utility of single-molecule SERS in practical applications, we present several examples of its use in various fields, including catalysis, imaging, and nanoelectronics. Finally, we specify current challenges in the development of single-molecule SERS and propose corresponding solutions.
The chiroptical effect is a property that describes distinct response of matter to light with opposite handedness, which is extensively utilized in stereochemistry, analytical chemistry, metamaterials, and spin photonics. Conventionally, metallic nanostructures have been harnessed to generate a strong chiroptical effect with the assistance of surface plasmon resonance, but they usually suffer from low energy efficiency and large photothermal heat generation due to the high ohmic loss of metallic materials, which severely restricts their practical applications. Here we present a dielectric spiral nanoflower with a giant chiroptical effect produced by magnetic resonance. We theoretically predicted the giant chiroptical effect of the spiral nanoflower by numerical simulations and analyzed its underlying physics by combination of a multipole expansion method. Based on the theoretical design, we experimentally fabricated the spiral nanoflower and demonstrated its strong chiroptical effect by characterizing its circular intensity difference (CID). The largest-to-date CID of 35% is demonstrated. The magnetic quadrupole interference within the spiral nanoflower was also clarified by experimentally tailoring its magnetic quadrupole interference. Our work is expected to overcome the limitation of conventional metallic platforms and pave the way toward the development of various highly efficient and thermostable chiroptical devices and applications.
Mid-infrared (MIR) resonators with high quality (Q) factors play crucial roles in a variety of applications in nonlinear optics, lasing, biochemical sensing, and spectroscopy by virtue of their features of long photon lifetime as well as strong field confinement and enhancement. Previously, such devices have been mainly studied on silicon integration platforms while the development of high-Q germanium resonators is still in its infancy due to quality limitations of current germanium integration platforms. Compared with silicon, germanium possesses a number of advantages for MIR applications, such as a wider transparency window (2 - 15 µm), a higher refractive index (~4), and a higher third-order nonlinear susceptibility. Here we present our experimental demonstration of two types of MIR high-Q germanium resonators, namely, a microring resonator and a photonic crystal nanobeam cavity. A maximum Q factor of ~57,000 is experimentally realized, which is the highest to date on germanium platforms. Moreover, we demonstrate a monolithic integration of the high-Q germanium resonators with suspended-membrane waveguides and focusing subwavelength grating couplers. Our resonators pave a new avenue for the study of on-chip light-germanium interactions and development of on-chip MIR applications in sensing and spectroscopy.
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