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Circulating tumor cell (CTC) clusters are present in cancer patients with severe metastasis, resulting in poor clinical outcomes. However, CTC clusters have not been studied as extensively as single CTCs, and the clinical utility of CTC clusters remains largely unknown. In this study, we aim sought to explore the feasibility of NanoVelcro Chips to simultaneously detect both single CTCs and CTC clusters with negligible perturbation to their intrinsic properties in neuroendocrine tumors (NETs). We discovered frequent CTC clusters in patients with advanced NETs and examined their potential roles, together with single NET CTCs, as novel biomarkers of patient response following peptide receptor radionuclide therapy (PRRT). We observed dynamic changes in both total NET CTCs and NET CTC cluster counts in NET patients undergoing PRRT which correlated with clinical outcome. These preliminary findings suggest that CTC clusters, along with single CTCs, offer a potential non-invasive option to monitor the treatment response in NET patients undergoing PRRT.

We investigated the effect of nanoscale curvature on the structure of thermally equilibrated poly-3-hexylthiophene (P3HT) ultrathin films. The curvature-induced effects were investigated with synchrotron grazing incidence X-ray diffraction (GIXRD) and atomic force microscopy (AFM). Our results demonstrate that nanoscale curvature reduces the polymer crystalline fraction and the crystal length. The first effect is strongest for the lowest curvature and results in a decrease in the out-of-plane thickness of the polymer crystals. On the other hand, the crystal in-plane length decreases with the increase in substrate curvature. Finally, the semi-quantitative analysis of crystal anisotropy shows a marked dependence on the substrate curvature characterized by a minimum at curvatures between 0.00851 nm−1 and 0.0140 nm−1. The results are discussed in terms of a curvature-dependent polymer fraction, which fills the interstices between neighboring particles and cannot crystallize due to extreme space confinement. This fraction, whose thickness is highest at the lowest curvatures, inhibits the crystal nucleation and the out-of-plane crystal growth. Moreover, because of the adhesion to the curved portion of the substrates, crystals adopt a random orientation. By increasing the substrate curvature, the amorphous fraction is reduced, leading to polymer films with higher crystallinity. Finally, when the thickness of the film exceeds the particle diameter, the curvature no longer affects the crystal orientation, which, similarly to the flat case, is predominantly edge on. [ABSTRACT FROM AUTHOR]

Tumor-derived extracellular vesicles (EVs) play essential roles in intercellular communication during tumor growth and metastatic evolution. Currently, little is known about the possible roles of tumor-derived EVs in sarcoma because the lack of specific surface markers makes it technically challenging to purify sarcoma-derived EVs. In this study, a specific purification system is developed for Ewing sarcoma (ES)-derived EVs by coupling covalent chemistry-mediated EV capture/ release within a nanostructure-embedded microchip. The purification platform-ES-EV Click Chip-takes advantage of specific anti-LINGO-1 recognition and sensitive click chemistry-mediated EV capture, followed by disulfide cleavage-driven EV release. Since the device is capable of specific and efficient purification of intact ES EVs with high purity, ES-EV Click Chip is ideal for conducting downstream functional studies of ES EVs. Absolute quantification of the molecular hallmark of ES (i.e., EWS rearrangements) using reverse transcription Droplet Digital PCR enables specific quantification of ES EVs. The purified ES EVs can be internalized by recipient cells and transfer their mRNA cargoes, exhibiting their biological intactness and potential role as biological shuttles in intercellular communication.

Unusual optical properties of laser-ablated metal surfaces arise from the excitation of local plasmon resonances in nano- and microstructures produced by laser-processing and from the mutual interaction of those structures through surface plasmon polariton (SPP) waves. This interaction provides a synergistic effect, which can make the optical properties of the composite nanostructure drastically different from the properties of its elements. At the same time, the prediction and analysis of these properties are hampered by the complexity of the analytical solution to the problem of SPP excitation by surface objects of arbitrary configuration. Such a problem can be reduced to a simpler one if one considers the geometry of a structured surface as a superposition of harmonic Fourier components. Therefore, the analytical solution to the problem of surface plasmon polariton excitation through the scattering of light by a sinusoidally perturbed plasmonic metal/vacuum boundary becomes very important. In this work, we show that this problem can be solved using a well-known method for calculating guided-mode amplitudes in the presence of current sources, which is used widely in the waveguide theory. The calculations are carried out for the simplest 2D cases of (1) a sinusoidal current of finite length and (2) a finite-length sinusoidal corrugation on a plasmonic metal surface illuminated by a normally incident plane wave. The analytical solution is compared with the results of numerical simulations. It is shown that, in the first case, the analytical and numerical solutions agree almost perfectly. In the second case, the analytical solution correctly predicts the optimum height of the corrugation x opt , providing the maximum SPP excitation efficiency. At the same time, the analytical and numerical values of the SPP amplitude agree very well when the corrugation height x turns out to be x ≪ x opt or x ≫ x opt (at least up to 3 x opt ); at x = x opt , the mismatch of those does not exceed 25%. The limitations of the analytical model leading to such a mismatch are discussed. We believe that the presented approach is useful for modeling various phenomena associated with SPP excitation. [ABSTRACT FROM AUTHOR]

Circulating rare cells in the blood are of great significance for both materials research and clinical applications. For example, circulating tumor cells (CTCs) have been demonstrated as useful biomarkers for "liquid biopsy" of the tumor. Circulating fetal nucleated cells (CFNCs) have shown potential in noninvasive prenatal diagnostics. However, it is technically challenging to detect and isolate circulating rare cells due to their extremely low abundance compared to hematologic cells. Nanostructured substrates offer a unique solution to address these challenges by providing local topographic interactions to strengthen cell adhesion and large surface areas for grafting capture agents, resulting in improved cell capture efficiency, purity, sensitivity, and reproducibility. In addition, rare-cell retrieval strategies, including stimulus-responsiveness and additive reagent-triggered release on different nanostructured substrates, allow for on-demand retrieval of the captured CTCs/CFNCs with high cell viability and molecular integrity. Several nanostructured substrate-enabled CTC/CFNC assays are observed maturing from enumeration and subclassification to molecular analyses. These can one day become powerful tools in disease diagnosis, prognostic prediction, and dynamic monitoring of therapeutic response-paving the way for personalized medical care.

We investigated the effect of nanoscale curvature on the structure of thermally equilibrated poly-3-hexylthiophene (P3HT) ultrathin films. The curvature-induced effects were investigated with synchrotron grazing incidence X-ray diffraction (GIXRD) and atomic force microscopy (AFM). Our results demonstrate that nanoscale curvature reduces the polymer crystalline fraction and the crystal length. The first effect is strongest for the lowest curvature and results in a decrease in the out-of-plane thickness of the polymer crystals. On the other hand, the crystal in-plane length decreases with the increase in substrate curvature. Finally, the semi-quantitative analysis of crystal anisotropy shows a marked dependence on the substrate curvature characterized by a minimum at curvatures between 0.00851 nm−1 and 0.0140 nm−1. The results are discussed in terms of a curvature-dependent polymer fraction, which fills the interstices between neighboring particles and cannot crystallize due to extreme space confinement. This fraction, whose thickness is highest at the lowest curvatures, inhibits the crystal nucleation and the out-of-plane crystal growth. Moreover, because of the adhesion to the curved portion of the substrates, crystals adopt a random orientation. By increasing the substrate curvature, the amorphous fraction is reduced, leading to polymer films with higher crystallinity. Finally, when the thickness of the film exceeds the particle diameter, the curvature no longer affects the crystal orientation, which, similarly to the flat case, is predominantly edge on.

Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of "tumor liquid biopsy". However, it is technically challenging to identify CTCs in patient blood samples because of the extremely low abundance of CTCs among a large number of hematologic cells. In order to address this challenge, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Four generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities. The 1st-gen NanoVelcro Chips, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, were created for CTC enumeration. The 2nd-gen NanoVelcro Chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation in conjunction with the use of the laser microdissection (LMD) technique. By grafting thermoresponsive polymer brushes onto SiNS, the 3rd-gen Thermoresponsive NanoVelcro Chips have demonstrated the capture and release of CTCs at 37 and 4 °C respectively, thereby allowing for rapid CTC purification while maintaining cell viability and molecular integrity. Fabricated with boronic acid-grafted conducting polymer-based nanomaterial on chip surface, the 4th-gen NanoVelcro Chips (Sweet chip) were able to purify CTCs with well-preserved RNA transcripts, which could be used for downstream analysis of several cancer specific RNA biomarkers. In this review article, we will summarize the development of the four generations of NanoVelcro CTC assays, and the clinical applications of each generation of devices.

Unusual optical properties of laser-ablated metal surfaces arise from the excitation of local plasmon resonances in nano- and microstructures produced by laser-processing and from the mutual interaction of those structures through surface plasmon polariton (SPP) waves. This interaction provides a synergistic effect, which can make the optical properties of the composite nanostructure drastically different from the properties of its elements. At the same time, the prediction and analysis of these properties are hampered by the complexity of the analytical solution to the problem of SPP excitation by surface objects of arbitrary configuration. Such a problem can be reduced to a simpler one if one considers the geometry of a structured surface as a superposition of harmonic Fourier components. Therefore, the analytical solution to the problem of surface plasmon polariton excitation through the scattering of light by a sinusoidally perturbed plasmonic metal/vacuum boundary becomes very important. In this work, we show that this problem can be solved using a well-known method for calculating guided-mode amplitudes in the presence of current sources, which is used widely in the waveguide theory. The calculations are carried out for the simplest 2D cases of (1) a sinusoidal current of finite length and (2) a finite-length sinusoidal corrugation on a plasmonic metal surface illuminated by a normally incident plane wave. The analytical solution is compared with the results of numerical simulations. It is shown that, in the first case, the analytical and numerical solutions agree almost perfectly. In the second case, the analytical solution correctly predicts the optimum height of the corrugation xopt, providing the maximum SPP excitation efficiency. At the same time, the analytical and numerical values of the SPP amplitude agree very well when the corrugation height x turns out to be x≪xopt or x≫xopt (at least up to 3xopt); at x=xopt, the mismatch of those does not exceed 25%. The limitations of the analytical model leading to such a mismatch are discussed. We believe that the presented approach is useful for modeling various phenomena associated with SPP excitation.

In the last few decades, plasmonic colorimetric biosensors raised increasing interest in bioanalytics thanks to their cost-effectiveness, responsiveness, and simplicity as compared to conventional laboratory techniques. Potential high-throughput screening and easy-to-use assay procedures make them also suitable for realizing point of care devices. Nevertheless, several challenges such as fabrication complexity, laborious biofunctionalization, and poor sensitivity compromise their technological transfer from research laboratories to industry and, hence, still hamper their adoption on large-scale. However, newly-developing plasmonic colorimetric biosensors boast impressive sensing performance in terms of sensitivity, dynamic range, limit of detection, reliability, and specificity thereby continuously encouraging further researches. In this review, recently reported plasmonic colorimetric biosensors are discussed with a focus on the following categories: (i) on-platform-based (localized surface plasmon resonance, coupled plasmon resonance and surface lattice resonance); (ii) colloid aggregation-based (label-based and label free); (iii) colloid non-aggregation-based (nanozyme, etching-based and growth-based). [ABSTRACT FROM AUTHOR]

Abstract Background Early detection of urothelial carcinoma (UC) by noninvasive diagnostic methods with high accuracy is still underscored. This study aimed to develop a noninvasive assay incorporating both enrichment of urine exfoliated cells and immunoassays for UC detection. Methods Polystyrene dishes were exposed to oxygen plasma and modified with 3‐aminopropyltriethoxysilane to prepare amine‐functionalized nanostructured substrates (NS). Performance characterization of NS was evaluated by atomic force microscope and X‐ray photoelectron spectroscopy. Urine exfoliated cells were captured by NS and then immunostained to detect urinary tumor cells (UTCs), which was called UTC assay. The receiver operating characteristic (ROC) curve, area under ROC curve (AUC), and Youden index were used to find the cutoff value of UTC assay. ROC analysis and McNemar test were used to compare the diagnostic accuracy of UTC assay with cytology. Kappa test was used to analyze the agreement of UTC assay and cytology with pathological diagnosis. Results Nanostructured substrates had good cell binding yields of nucleated cells and tumor cells. CK20+CD45−CD11b− cells were considered as UTCs. UTC number ≥ 1 per sample could be considered as a positive result. By AUC and Kappa analysis, UTC assay showed good performance in UC detection. McNemar test demonstrated that UTC assay had a superior sensitivity even in low‐grade subgroup and a similar specificity compared to cytology in UC diagnosis. Conclusions Nanostructured substrates could be used to enrich the exfoliated cells from urine samples. UTC assay with NS has the potential to play a role in UC detection. The value of this assay still needs additional validation by large, multi‐center studies.

Within the past two decades, the escalation of research output in nanotechnology fields has boosted the development of novel nanoparticles and nanostructured substrates for use as matrices in surface assisted laser desorption/ionization mass spectrometry (SALDI‐MS). The application of nanomaterials as matrices, rather than organic matrices, offers remarkable characteristics that allow the analysis of small molecules with fewer matrix interfering peaks, and share higher detection sensitivity, specificity, and reproducibility. The technological advancement of SALDI‐MS has in turn, propelled the application of the analytical technique in the field of biomedical analysis. In this review, the properties and fabrication methods of nanostructured substrates in SALDI‐MS such as metallic‐, carbon‐, and silicon‐based nanostructures, quantum dots, metal‐organic frameworks, and covalent‐organic frameworks are described. Additionally, the latest progress (most within 5 years) of biomedical applications in small molecule, large biomolecule, and MS imaging analysis including metabolite profiling, drug monitoring, bacteria identification, disease diagnosis, and therapeutic evaluation are demonstrated. Key parameters that govern nanomaterial's SALDI efficiency in biomolecule analysis are also discussed. Finally, perspectives of the future development are given to provide a better advancement and promote practical application in clinical MS. [ABSTRACT FROM AUTHOR]

In the last few decades, plasmonic colorimetric biosensors raised increasing interest in bioanalytics thanks to their cost-effectiveness, responsiveness, and simplicity as compared to conventional laboratory techniques. Potential high-throughput screening and easy-to-use assay procedures make them also suitable for realizing point of care devices. Nevertheless, several challenges such as fabrication complexity, laborious biofunctionalization, and poor sensitivity compromise their technological transfer from research laboratories to industry and, hence, still hamper their adoption on large-scale. However, newly-developing plasmonic colorimetric biosensors boast impressive sensing performance in terms of sensitivity, dynamic range, limit of detection, reliability, and specificity thereby continuously encouraging further researches. In this review, recently reported plasmonic colorimetric biosensors are discussed with a focus on the following categories: (i) on-platform-based (localized surface plasmon resonance, coupled plasmon resonance and surface lattice resonance); (ii) colloid aggregation-based (label-based and label free); (iii) colloid non-aggregation-based (nanozyme, etching-based and growth-based).

Background: Early detection of urothelial carcinoma (UC) by noninvasive diagnostic methods with high accuracy is still underscored. This study aimed to develop a noninvasive assay incorporating both enrichment of urine exfoliated cells and immunoassays for UC detection. Methods: Polystyrene dishes were exposed to oxygen plasma and modified with 3‐aminopropyltriethoxysilane to prepare amine‐functionalized nanostructured substrates (NS). Performance characterization of NS was evaluated by atomic force microscope and X‐ray photoelectron spectroscopy. Urine exfoliated cells were captured by NS and then immunostained to detect urinary tumor cells (UTCs), which was called UTC assay. The receiver operating characteristic (ROC) curve, area under ROC curve (AUC), and Youden index were used to find the cutoff value of UTC assay. ROC analysis and McNemar test were used to compare the diagnostic accuracy of UTC assay with cytology. Kappa test was used to analyze the agreement of UTC assay and cytology with pathological diagnosis. Results: Nanostructured substrates had good cell binding yields of nucleated cells and tumor cells. CK20+CD45−CD11b− cells were considered as UTCs. UTC number ≥ 1 per sample could be considered as a positive result. By AUC and Kappa analysis, UTC assay showed good performance in UC detection. McNemar test demonstrated that UTC assay had a superior sensitivity even in low‐grade subgroup and a similar specificity compared to cytology in UC diagnosis. Conclusions: Nanostructured substrates could be used to enrich the exfoliated cells from urine samples. UTC assay with NS has the potential to play a role in UC detection. The value of this assay still needs additional validation by large, multi‐center studies. [ABSTRACT FROM AUTHOR]

In the present work, a novel technological approach based on ion implantation for obtaining microstructured substrates for the statistical analysis and visual characterization of ultra-small biological objects and microorganisms is developed. By means of the argon-ion implantation of silicate glasses through surface masks made of wire mesh, periodic surface nanostructures in the form of gratings with mesh sizes of 500 × 500 nm are formed. The obtained novel substrates are tested using atomic force microscopy and scanning electron microscopy with energy dispersive analysis using bacteria of the genus Bacillus deposited onto their surface. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cell (CTC) isolation methods based on nanostructured substrates can be used to isolate tumor cells from peripheral blood. This study aimed to validate the clinical application of our method and determine the appropriate diagnostic critical value. Methods: AFM was used to detect the surface roughness of nanostructured substrates. Cell lines and blood samples were used to verify CTC isolation methods. The ROC curve and AUC were used to evaluate the diagnostic value of CTC numbers. Results: First, AFM, cell binding yields, and tumor cell detection rate from blood showed that NS has a potential for cell adsorption. Then, the CTC detection method was verified by using cell lines and blood samples. The number of CTCs in patients with cancers or metastases were significantly greater than those of patients without cancers. Then, the ROC curves and AUC showed that this method had a medium diagnostic value. Conclusions: Isolating CTCs based on nanostructured substrates was appropriate for the clinical diagnosis of tumors, and samples with more than 1.5 CTCs/1 mL blood could be identified as CTC-positive. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering is a well-established technique for molecular detection at low concentration, which is becoming increasingly popular in the field of biotechnology and health sciences. Since the process is understood in depth, the technique is becoming reliable. In this contribution, we consider another aspect of SERS besides molecular detection, focusing on the binding mechanisms of a complex system such as a protein to the noble metal substrates required by the technique itself. We also show that using a solid nanostructured substrate produced by controlled pulsed laser deposition SERS enables label-free detection of a protein. This is checked on lysozyme as a well-known prototype. Use of solid substrates with controlled morphology proves advantageous over colloidal systems for SERS applications. Moreover, such substrates are superior in terms of shelf life, packaging and ease of shipment. [ABSTRACT FROM AUTHOR]

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) is an excellent analytical technique for rapid and sensitive analysis of macromolecules such as polymers and proteins. However, the main drawback of MALDI‐TOF MS is its difficulty to detect small molecules with mass below 700 Da because of the intensive interference from MALDI matrix in the low mass region. In recent years there has been considerable interest in developing matrix‐free laser desorption/ionization by using nanostructured substrates to substitute the conventional organic matrices, which is often referred as surface‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (SALDI‐TOF MS). Despite these attractive features, most of the current SALDI‐TOF MS for the analysis of small molecules employ positive ion mode, which is subjected to produce multiple alkali metal adducts, and thus increases the complexity of the analysis. Different from the complicated adducts produced in positive ion mode, mass spectra obtained in negative ion mode are featured by deprotonated ion peaks without matrix interference, which simplifies the interpretation of mass spectra and detection of unknown. In this review, we critically survey recent advances in nanostructured substrates for negative ion LDI‐TOF MS analysis of small molecules in the last 5 years. Special emphasis is placed on the preparation of the nanostructured substrates and the results achieved in negative ion SALDI‐MS. In addition, a variety of promising applications including environmental, biological, and clinical analysis are introduced. The ionization mechanism of negative ionization is briefly discussed. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are a hallmark of invasive behavior of cancer, responsible for the development of metastasis. Their detection and analysis have significant impacts in cancer biology and clinical practice. However, CTCs are rare events and contain heterogeneous subpopulations, requiring highly sensitive and specific techniques to identify and capture CTCs with high efficiency. Nanotechnology shows strong promises for CTC enrichment and detection owning to the unique structural and functional properties of nanoscale materials. In this review, we discuss the CTC enrichment and detection technologies based on a variety of functional nanosystems and nanostructured substrates, with the goal to highlight the role of nanotechnology in the advancement of basic and clinical CTC research. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are cancer cells that shed from the primary tumor and then enter the circulatory system, a small part of which may evolve into metastatic cancer under appropriate microenvironment conditions. The detection of CTCs is a truly noninvasive, dynamic monitor for disease changes, which has considerable clinical implications in the selection of targeted drugs. However, their inherent rarity and heterogeneity pose significant challenges to their isolation and detection. Even the "gold standard", CellSearch™, suffers from high expenses, low capture efficiency, and the consumption of time. With the advancement of CTCs analysis technologies in recent years, the yield and efficiency of CTCs enrichment have gradually been improved, as well as detection sensitivity. In this review, the isolation and detection strategies of CTCs have been completely described and the potential directions for future research and development have also been highlighted through analyzing the challenges faced by current strategies. Circulating tumor cells (CTCs) are cancer cells that shed from the primary tumor and then enter the circulatory system, a small part of which may evolve into metastatic cancer under appropriate microenvironment conditions. In this review, the isolation and detection strategies of CTCs have been completely described and the potential directions for future research and development have also been highlighted through analyzing the challenges faced by current strategies. [Display omitted] • Magnetic separation, nanostructured substrates, and microfluidics technologies for the isolation of CTCs are summarized. • Different CTCs detection methods are discussed including fluorescence, ICP-MS, SERS, and electrochemistry methods. • An overview of the existing difficulties and prospects for CTCs study in this field is provided. [ABSTRACT FROM AUTHOR]

• Potential blood-based biosources in cancer liquid biopsy were introduced. • We reviewed nanoparticle-labeled with targeting-moieties, nanostructured substrates and nanobiosensors in liquid biopsy. • The mechanisms and methods of using functional nanoparticles to capture and recover CTCs were summarized. • Nanotechnology-mediated downstream analysis and elimination of CTCs were also discussed. • We offered an outlook on the challenges and suggestions for nanotechnology-based cancer liquid biopsy. The applications of nanotechnology on the detection, recovery, analysis, and elimination of liquid biopsy components in cancer. [Display omitted] Liquid biopsy allows for the quick and noninvasive detection of tumor-associated components. Various liquid biopsy components, which include circulating tumor cells, tumor-derived extracellular vesicles, circulating tumor nucleic acids, and tumor-educated platelets, can be analyzed. These components hold great potential for tracking the evolutionary dynamics of tumors and detecting the early emergence of therapeutic resistance and tumor recurrence. In recent decades, significant advances in nanotechnology have contributed to the development of blood-based liquid biopsy with higher sensitivity and specificity. This review discusses the key nanotechnologies that can be used to detect, isolate, and recover tumor-associated components, providing a brief overview of the downstream analysis of these components and then focusing on the different types of nanomaterials that can be applied for the treatment of circulating tumor cells to prevent metastasis. Taken together, these noninvasive nanotechnology-mediated diagnostic approaches can aid precise cancer assessment and guide modifications to current treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract: Starting from their discovery in 1991, carbon nanotubes have attracted a great attention, thanks to their peculiar mechanical, electrical and elastic properties that could be used to realize new devices in many different fields. For nanotechnology applications it is very important to be able to control not only shape and position but also alignment and orientation of carbon nanotubes, both during the growth and after it. Here we present preliminary results obtained by depositing carbon nanotubes (CNT) solutions on ion sputtered quartz substrates. Atomic force microscopy (AFM) images allow to study both CNTs positioning on the “ripples” generated by Ar+ sputtering on the SiO2 surface and their radial deformation induced by the “rough” surface. Work is now in progress to optimize the sputtering parameters and solution treatment (purification and functionalization) in order to get single CNTs regularly arranged on a patterned surface. [Copyright &y& Elsevier]

Circulating tumor cell (CTC) clusters are present in cancer patients with severe metastasis, resulting in poor clinical outcomes. However, CTC clusters have not been studied as extensively as single CTCs, and the clinical utility of CTC clusters remains largely unknown. In this study, we aim sought to explore the feasibility of NanoVelcro Chips to simultaneously detect both single CTCs and CTC clusters with negligible perturbation to their intrinsic properties in neuroendocrine tumors (NETs). We discovered frequent CTC clusters in patients with advanced NETs and examined their potential roles, together with single NET CTCs, as novel biomarkers of patient response following peptide receptor radionuclide therapy (PRRT). We observed dynamic changes in both total NET CTCs and NET CTC cluster counts in NET patients undergoing PRRT which correlated with clinical outcome. These preliminary findings suggest that CTC clusters, along with single CTCs, offer a potential non-invasive option to monitor the treatment response in NET patients undergoing PRRT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sarcoma-Derived Extracellular Vesicles: Coupling Nanostructured Microchips with Covalent Chemistry Enables Purification of Sarcoma-Derived Extracellular Vesicles for Downstream Functional Studies (Adv. Funct. Keywords: covalent chemistry; extracellular vesicles; microfluidics; nanostructured substrates; sarcoma EN covalent chemistry extracellular vesicles microfluidics nanostructured substrates sarcoma 1 1 1 12/03/20 20201201 NES 201201 In article number 2003237, Meiping Zhao, Hsian-Rong Tseng, Yazhen Zhu, and co-workers present a device for the purification of Ewing sarcoma-derived extracellular vesicles (EVs) by coupling LINGO-1 antibodies with the covalent chemistry-mediated EV capture/release mechanism using a nanostructure-embedded microchip. Covalent chemistry, extracellular vesicles, microfluidics, nanostructured substrates, sarcoma. [Extracted from the article]

Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of "tumor liquid biopsy". However, it is technically challenging to identify CTCs in patient blood samples because of the extremely low abundance of CTCs among a large number of hematologic cells. In order to address this challenge, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Four generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities. The 1st-gen NanoVelcro Chips, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, were created for CTC enumeration. The 2nd-gen NanoVelcro Chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation in conjunction with the use of the laser microdissection (LMD) technique. By grafting thermoresponsive polymer brushes onto SiNS, the 3rd-gen Thermoresponsive NanoVelcro Chips have demonstrated the capture and release of CTCs at 37 and 4 °C respectively, thereby allowing for rapid CTC purification while maintaining cell viability and molecular integrity. Fabricated with boronic acid-grafted conducting polymer-based nanomaterial on chip surface, the 4th-gen NanoVelcro Chips (Sweet chip) were able to purify CTCs with well-preserved RNA transcripts, which could be used for downstream analysis of several cancer specific RNA biomarkers. In this review article, we will summarize the development of the four generations of NanoVelcro CTC assays, and the clinical applications of each generation of devices., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Surfaces contaminated with pathogenic microorganisms contribute to their transmission and spreading. The development of "active surfaces" that can reduce or eliminate this contamination necessitates a detailed understanding of the molecular mechanisms of interactions between the surfaces and the microorganisms. Few studies have shown that, among the different surface characteristics, the wetting properties play an important role in reducing virus infectivity. Here, we systematically tailored the wetting characteristics of flat and nanostructured glass surfaces by functionalizing them with alkyl- and fluoro-silanes. We studied the effects of these functionalized surfaces on the infectivity of Influenza A viruses using a number of experimental and computational methods including real-time fluorescence microscopy and molecular dynamics simulations. Overall, we show that surfaces that are simultaneously hydrophobic and oleophilic are more efficient in deactivating enveloped viruses. Our results suggest that the deactivation mechanism likely involves disruption of the viral membrane upon its contact with the alkyl chains. Moreover, enhancing these specific wetting characteristics by surface nanostructuring led to an increased deactivation of viruses. These combined features make these substrates highly promising for applications in hospitals and similar infrastructures where antiviral surfaces can be crucial.