Label-free optical imaging of nanoscale objects faces fundamental challenges. Techniques based on propagating surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) have shown promises. However, challenges remain to achieve diffraction-limited resolution and better surface localization in SPR imaging. LSPR imaging with dark-field microscopy on metallic nanostructures suffers from low light throughput and insufficient imaging capacity. Here we show ultra-near-field index modulated PlAsmonic NanO-apeRture lAbel-free iMAging (PANORAMA) which uniquely relies on unscattered light to detect sub-100 nm dielectric nanoparticles. PANORAMA provides diffraction-limited resolution, higher surface sensitivity, and wide-field imaging with dense spatial sampling. Its system is identical to a standard bright-field microscope with a lamp and a camera – no laser or interferometry is needed. In a parallel fashion, PANORAMA can detect, count and size individual dielectric nanoparticles beyond 25 nm, and dynamically monitor their distance to the plasmonic surface at millisecond timescale. Here, the authors report on an imaging method based on localized surface plasmon resonance excitation, employing gold nanodisk arrays as substrates that enable imaging of transparent dielectric particles of several sizes. They demonstrate the ability to detect and image particles smaller than the diffraction limit at 25 nm with standard bright-field imaging.

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Plasmonic nano-aperture label-free imaging (PANORAMA)

The roles of small extracellular vesicles in lung cancer: Molecular pathology, mechanisms, diagnostics, and therapeutics.

Extracellular vesicles (EVs) are a group of communication organelles enclosed by a phospholipid bilayer, secreted by all types of cells. The size of these vesicles ranges from 30 to 1000 nm, and they contain a myriad of compounds such as RNA, DNA, proteins, and lipids from their origin cells, offering a good source of biomarkers. Exosomes (30 to 100 nm) are a subset of EVs, and their importance in future medicine is beyond any doubt. However, the lack of efficient isolation and detection techniques hinders their practical applications as biomarkers. Versatile and cutting-edge platforms are required to detect and isolate exosomes selectively for further clinical analysis. This review paper focuses on lab-on-chip devices for capturing, detecting, and isolating extracellular vesicles. The first part of the paper discusses the main characteristics of different cell-derived vesicles, EV functions, and their clinical applications. In the second part, various microfluidic platforms suitable for the isolation and detection of exosomes are described, and their performance in terms of yield, sensitivity, and time of analysis is discussed.

/pdf/microfluidic-platforms-for-the-isolation-and-detection-of-1nowf38x.pdf

Microfluidic Platforms for the Isolation and Detection of Exosomes: A Brief Review

Label-free observation of nanoparticles by far-field optical microscopy is challenging because their ability to scatter or absorb light dramatically diminishes with decreasing size. Surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR) imaging have shown promises and respective limitations. For instance, it is challenging to achieve diffraction-limited resolution in SPR imaging; its refractive index sensitivity is not as localized as desired. LSPR imaging is typically employed with dark-field microscopy on sparse noble metal nanostructures, leading to low light throughput and incomplete imaging. Here we demonstrate ultra near-field index modulated PlAsmonic NanO-apeRture lAbel-free iMAging (PANORAMA) that addresses existing issues for both SPR and LSPR imaging. PANORAMA produces diffraction-limited lateral resolution with higher surface sensitivity compared to SPR. Its system configuration is identical to a standard bright-field microscope using a trans-illumination tungsten-halogen lamp instead of a laser or other high-intensity light sources. Additionally, PANORAMA addresses the sparse sampling issue in LSPR imaging by achieving dense sampling with a large imaging fill factor. The bright-field approach provides much higher light throughput compared to dark-field microscopy. Overall, our technique can provide a panoramic view both laterally and longitudinally - overcoming the lack of imaging depth for both SPR and LSPR imaging and the insufficient lateral sampling for LSPR imaging. We have demonstrated that PANORAMA can size single nanoparticle down to 25 nm, count individual nanoparticles in a cluster, and dynamically monitor single nanoparticle approaching the plasmonic surface down to the millisecond timescale. PANORAMA is potentially useful in single biological nanoparticle analysis of exosomes and viruses.

Plasmonic nano-aperture label-free imaging

Directed concentrating of micro- and nanoparticles via laser-generated plasmonic microbubbles in a liquid environment is an emerging technology. For effective heating, visible light has been primarily employed in existing demonstrations. In this paper, we demonstrate a new plasmonic platform based on nanoporous gold disk (NPGD) array. Thanks to the highly tunable localized surface plasmon resonance of the NPGD array, microbubbles of controlled size can be generated by near-infrared (NIR) light. Using NIR light provides several key advantages over visible light in less interference with standard microscopy and fluorescence imaging, preventing fluorescence photobleaching, less susceptible to absorption and scattering in turbid biological media, and much reduced photochemistry, phototoxicity, and so forth. The large surface-to-volume ratio of NPGD further facilitates the heat transfer from these gold nanoheaters to the surroundings. While the microbubble is formed, the surrounding liquid circulates and direct microparticles randomly dispersed in the liquid to the bottom NPGD surface, which can be made to yield a unique collection of 3D hollow dome microstructures with bubbles larger than 5 μm. Such capability can also be employed in concentrating suspended colloidal nanoparticles at desirable sites and with the preferred configuration enhancing the sensor performance. Specifically, the interaction among concentrated nanoparticles and their interactions with the underlying substrate have been investigated for the first time. These collections have been characterized using optical microscopy, scanning electron microscopy, hyperspectral localized surface plasmon resonance imaging, and hyperspectral Raman imaging. In addition to various micro- and nanoparticles, the plasmonic microbubbles are also shown to collect biological cells and extracellular nanovesicles such as exosomes. By using a spatial light modulator to project the laser in arbitrary patterns, parallel concentrating can be achieved to fabricate an array of clusters.

Directed Concentrating of Micro-/Nanoparticles via Near-Infrared Laser Generated Plasmonic Microbubbles.

https://iopscience.iop.org/article/10.1088/2515-7647/ab8699/pdf

Commercial and emerging technologies for cancer diagnosis and prognosis based on circulating tumor exosomes

Nareg Ohannesian,1 Dilani Gunawardhana,1 Ibrahim Misbah,1 Mohsen Rakhshandehroo,1 Steven H. Lin,5 and Wei-Chuan Shih1,2,3,4,* 1Department of Electrical and Computer Engineering 2Department of Biomedical Engineering 3Department of Chemistry 4Program of Materials Science and Engineering University of Houston, 4800 Calhoun Road, Houston, Texas 77204, USA 5Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. *Corresponding author: wshih@uh.edu Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 31 January 2020

https://www.preprints.org/manuscript/202001.0379/v1/download

Commercial and Emerging Technologies for Cancer Diagnosis and Prognosis Based on Exosomal Biomarkers

Holographic optical tweezers (HOT) is an effective means for optical manipulation. Herein we demonstrate its integration with imaging spectroscopy for biological and biomedical applications.

Mohsen Rakhshandehroo

Papers

Commercial and emerging technologies for cancer diagnosis and prognosis based on circulating tumor exosomes

Commercial and Emerging Technologies for Cancer Diagnosis and Prognosis Based on Exosomal Biomarkers

Holographic optical tweezers assisted imaging spectroscopy