Isolation Technology Research Articles

Efficient EVs separation and detection by an alumina-nanochannel-array-membrane integrated microfluidic chip and an antibody barcode biochip

BackgroundSmall endosome-derived lipid nanovesicles (30–200 nm) are actively secreted by living cells and serve as pivotal biomarkers for early cancer diagnosis. However, the study of extracellular vesicles (EVs) requires isolation and purification from various body fluids. Although traditional EVs isolation and detection technologies are mature, they usually require large amount of sample, consumes long-time, and have relatively low-throughput. How to efficiently isolate, purify and detect these structurally specific EVs from body fluids with high-throughput remains a great challenge in in vitro diagnostics and clinical research. ResultsHerein, we suggest a nanosized microfluidic device for efficient and economical EVs filtration based on an alumina nanochannel array membrane. We evaluated the filtration device performance of alumina membranes with different diameters and found that an optimized chamber array with a hydrophilic-treated channel diameter of 90 nm could realize a filtration efficiency of up to 82% without any assistance from chemical or physical separation methods. Importantly, by integrating meticulously designed multichannel microfluidic biochips, EVs can be captured in-situ and monitored by antibody barcode biochip. The proposed filtration chip together with the high-throughput detection chip were capable of filtration of a few tens of μL samples and recognition of different phonotypes. The practical filtration and detection of EVs from clinical samples demonstrated the high performance of the device. SignificantOverall, this work provides a cost-effective, highly efficient and automated EVs filtration chip and detection dual-function integrated chip platform, which can directly separate EVs from serum or cerebrospinal fluid with an efficiency of 82% and conduct in-situ detection. This small fluidic device can provide a powerful tool for highly efficient identifying and analyzing EVs, presenting great application potential in clinical detection.

The Use of Mobile Technologies in Post-Pandemic Times: Teacher Agency in the View of the Ecological Approach

Digital technologies play a vital role in social, political, and economic relations in contemporary society. These technologies were prevalent during the pandemic, and teachers’ lived experiences through that time can serve as a starting point for post-pandemic reflections. The study aims to investigate: i) the situations and the context that contributed to the current perception about the use of the smartphone for teachers’ education and work, ii) the way inclusive pedagogies can be integrated into the teachers’ praxis to ensure everyone’s access to education and to what extent can smartphones be used to support actions with a view to social transformation. The participants in this study are pre-service language teachers from the School of Letters – Federal University of Minas Gerais, Brazil. Data was generated through the use of a questionnaire. The findings indicate the indissociable connection between the context and the exercise of teacher agency. Technology in isolation is not a lever for transformation, but mobile technology, when ecologically situated and critically used, can become a force for change.

Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation.

Background: MicroRNA (miRNA) have the potential to be non-invasive and attractive biomarkers for a vast number of diseases and clinical conditions; however, a reliable analysis of miRNA expression in blood samples meets a number of methodological challenges. In this report, we presented and discussed, specifically, the principles and limitations of miRNA purification and analysis in blood plasma samples collected from the left atrium during an ablation procedure on patients with atrial fibrillation (AF). Materials and Methods: Consecutive patients hospitalized in the First Department of Cardiology for pulmonary vein ablation were included in this study (11 with diagnosed paroxysmal AF, 14 with persistent AF, and 5 without AF hospitalized for left-sided WPW ablation-control group). Whole blood samples were collected from the left atrium after transseptal puncture during the ablation procedure of AF patients. Analysis of the set of miRNA molecules was performed in blood plasma samples using the MIHS-113ZF-12 kit and miScript microRNA PCR Array Human Cardiovascular Disease. Results: The miRNS concentrations were in the following ranges: paroxysmal AF: 7-23.1 ng/µL; persistent AF: 4.9-66.8 ng/µL; controls: 6.3-10.6 ng/µL. The low A260/280 ratio indicated the protein contamination and the low A260/A230 absorbance ratio suggested the contamination by hydrocarbons. Spectrophotometric measurements also indicated low concentration of nucleic acids (<10 ng/µL). Further steps of analysis revealed that the concentration of cDNA after the Real-Time PCR (using the PAXgene RNA Blood kit) reaction was higher (148.8 ng/µL vs. 68.4 ng/µL) and the obtained absorbance ratios (A260/A280 = 2.24 and A260/A230 = 2.23) indicated adequate RNA purity. Conclusions: Although developments in miRNA sequencing and isolation technology have improved, detection of plasma-based miRNA, low RNA content, and sequencing bias introduced during library preparation remain challenging in patients with AF. The measurement of the quantity and quality of the RNA obtained is crucial for the interpretation of an efficient RNA isolation.

Abstract 3705: Development and analytical validation of a novel assay for HER2 assessment on circulating tumor cells using Parsortix® isolation and BioView imaging technologies

Abstract Background. HER2 testing in tissue biopsies is extensively performed in breast cancer (BC) patients. However, tissue biopsy is invasive and repeated examination is impractical. Additionally, lack of concordance between primary tumor and metastatic sites are often observed. Liquid biopsy, on the other hand, enables less invasive and recurrent sample collection for ongoing monitoring. In this study, we developed an end-to-end Research Use Only assay for concomitant evaluation of HER2 gene amplification and protein overexpression in circulating tumor cells (CTCs). Methods. Blood was drawn from healthy volunteers into Streck Cell-Free DNA tubes, spiked with SKBR3 (HER2+) and Hs 578T (HER2-) breast cancer cells and processed on ANGLE's Parsortix® PC1 System, a microfluidic device that captures CTCs from metastatic breast cancer patients’ blood based on their size and deformability, without relying on specific markers. Captured cells were harvested and spun onto positively charged slides and stained with the Portrait HER2 immunofluorescence (IF) panel, consisting of a nuclear dye, epithelial and mesenchymal markers, leukocytes’ markers, and an antibody targeting HER2. Slides were then de-stained and subjected to HER2 FISH using a commercially available kit. All slides were imaged twice using BioView Allegro Plus, a platform equipped with artificial intelligence for automated imaging, CTC candidate identification and reporting. First, an automated scan after IF was performed to identify CTCs based on marker expression and morphology profiles. Second, an automated relocation of the CTCs based on IF results and reimaging using higher magnification to ensure precise analysis of the FISH signals in single cells. The workflow is being implemented in a cohort of BC patients. Results. Following IF, HER2 protein expression in SKBR3 cells was significantly higher (p&amp;lt;0.0001) than that of HER2-negative cells, with 100% analytical specificity and sensitivity. Following FISH, 100% of the cells were de-stained and presented sharp HER2/CEP17 foci, with 96% of the SKBR3 cells and only 4% of the Hs 578T cells displaying HER2 amplification. Additionally, in a small cohort of metastatic BC patients’, 100% of the identified CTCs are retained and evaluable from IF to FISH. Conclusions. An assay integrating HER2 identification by IF and FISH to characterize CTCs in metastatic BC patients was successfully developed. The assay enables the identification of both HER2 protein and gene copy information from each target cell with minimal cell loss, with the potential for minimally invasive patient monitoring during treatment and better classification of patients who may qualify and benefit from HER2-targeted therapies. An added value of the assay is the practicality of utilizing preserved blood samples, allowing streamline batch shipping of clinical samples. Citation Format: Mariacristina Ciccioli, Alex Young, Laila Vlietinck, Chassidy Johnson, Anne-Sophie Pailhes-Jimenez. Development and analytical validation of a novel assay for HER2 assessment on circulating tumor cells using Parsortix® isolation and BioView imaging technologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3705.

Abstract 3801: Spatially resolved laser-activated cell sorting (SLACS) for high throughput spatial cell sorting in tumor research

Abstract Understanding of tumor heterogeneity and the microenvironment is a cornerstone in advancing cancer research and therapy. The Spatially resolved Laser-Activated Cell Sorter (SLACS) represents a novel approach in cancer research, allowing for high-throughput, precise cell isolation while preserving spatial information, which is crucial for studying tumor heterogeneity and the tumor microenvironment. The SLACS instrument utilizes laser-activated technology for selective isolation of cells from heterogeneous tissue samples, optimized for accuracy, speed, and minimal cell damage. This instrument has demonstrated effective isolation of specific cell types from complex tissue matrices, maintaining cell integrity and spatial information. Its high-throughput capacity significantly reduces sample processing time. This groundbreaking tool offers detailed exploration of tumor heterogeneity and the tumor microenvironment, providing valuable insights into cancer biology and potential therapeutic targets. Citation Format: Sumin Lee, Amos Chungwon Lee. Spatially resolved laser-activated cell sorting (SLACS) for high throughput spatial cell sorting in tumor research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3801.

Abstract 6331: A novel automated platform for rapid manufacturing of CAR T cells

Abstract Autologous cell therapy using genetically modified T cells to express chimeric antigen receptor (CAR) has yielded durable responses in cancers patients. However, currently only a small portion of patients are privileged to receive the treatment. High cost and long manufacturing time contribute to the key limitations prohibiting cell therapy broad adoption. Researchers discovered that reducing ex vivo culture improves anti-tumor activity of CAR T cells1 and recently demonstrated the process of generating functional CAR T cells within 24 hours2. This rapid process provides great promise in cost reduction of CAR T therapy and opportunity to have cells manufactured in close-to-patient settings. CART cell manufacturing process involves: (1) collection of peripheral blood; (2) isolation of T cells; (3) performing transduction via viral vector; (4) washing CAR T cells to remove viral vector, and (5) harvesting CAR T cells in IV fluid. Conventional process uses magnetic separation and serial centrifugation technologies on multiple platforms with manual operations. Here we demonstrate the feasibility of rapid manufacturing CAR T cells on an automated platform with closed fluidics without centrifugation steps. The platform, MARS® Atlas, is built with innovative technologies in immune-magnetic cell isolation and acoustic cell washing and implemented as a modular system. In this feasibility test, T cells were isolated from peripheral blood from a healthy donoron MARS® magnetic module. eGFP expressing lentivirus were added to the enriched T cells. After short incubation, cells and virus were washed with fresh medium on the MARS® acoustic module and cells were incubated with virus overnight without activation. Infected cells were washed on the acoustic module to remove free virus. Product CAR T cells were harvested in saline solution and ready for QC analysis. Starting from 20mL of peripheral blood, magnetic T cell separation was done 2mL/min achieving 90% T cell purity, 90% recovery. In the first acoustic wash, medium exchange of the mixture of cells and virus took place at 0.9mL/min flow rate. As a result, 90% removal of contaminating molecule and 99.6% recovery of T cells were achieved. The second acoustic wash completed medium exchange of transfected cells at 0.9mL/min with 96.7% removal of virus and 90% CAR T cell recovery. As a result, 18 million GFP expressing T cells were produced. In this study we have demonstrated the feasibility of rapidly manufacturing CAR-T cells on an automated platform MARS® Atlas. This result indicates the MARS® Atlas being a potential CAR T manufacturing platform to be used in close-to-patient settings to enable low-cost cell therapy. 1 Saba Ghassemi, Reducing Ex Vivo Culture Improves the Antileukemic Activity of Chimeric Antigen Receptor (CAR) T Cells, Cancer Immunol Res; 6(9) September 2018 2 Saba Ghassemi, Rapid manufacturing of non-activated potent CAR T cells, Nature Biomedical Engineering | VOL 6 | February 2022 | 118-128 Citation Format: Silin Sa, Ethan Nguyen, Jie Pan, Liping Yu. A novel automated platform for rapid manufacturing of CAR T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6331.

Pulsed field ablation technology for pulmonary vein and left atrial posterior wall isolation in patients with persistent atrial fibrillation.

Limited data exist on pulsed-field ablation (PFA) in patients with persistent atrial fibrillation (PeAF) undergoing left atrial posterior wall isolation (LAPWI). The Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice (ATHENA) prospective registry included consecutive patients referred for PeAF catheter ablation at 9 Italian centers, treated with the FARAPULSETM-PFA system. The primary efficacy and safety study endpoints were the acute LAPWI rate, freedom from arrhythmic recurrences and the incidence of major periprocedural complications. Patients undergoing pulmonary vein isolation (PVI) alone, PWI + LAPWI and redo procedures were compared. Among 249 patients, 21.7% had long-standing PeAF, 79.5% were male; mean age was 63 ± 9 years. LAPWI was performed in 57.6% of cases, with 15.3% being redo procedures. Median skin-to-skin times (PVI-only 68 [60-90] vs. PVI + LAPWI 70 [59-88] mins) did not differ between groups. 45.8% LAPWI cases were approached with a 3D-mapping system, and 37.3% with intracardiac echocardiography. LAPWI was achieved in all patients by means of PFA alone, in 88.8% cases at first pass. LAPWI was validated either by an Ultrahigh-density mapping system or by recording electrical activity + pacing maneuvers. No major complications occurred, while 2.4% minor complications were detected. During a median follow-up of 273 [191-379] days, 41 patients (16.5%) experienced an arrhythmic recurrence after the 90-day blanking period, with a mean time to recurrence of 223 ± 100 days and no differences among ablation strategies. LAPWI with PFA demonstrates feasibility, rapidity, and safety in real-world practice, offering a viable alternative for PeAF patients. LAPWI is achievable even with a fluoroscopy-only method and does not significantly extend overall procedural times.

Abstract 6563: PSMA-based detection and global proteome-based analysis of circulating tumor cells in castration resistant prostate cancer patients

Abstract In recent years, many new targeted and immuno-therapies have entered the cancer treatment landscape with the potential to drastically improve patient outcomes; however, selecting the optimal drug target especially as the disease progresses becomes increasingly important. Liquid biopsies show great promise in providing insights on the current disease state, but generally rely on a small number of protein markers identified through immunofluorescence staining or genomic mutations determined from cell-free DNA which limits the amount of information available to make treatment decisions. One way to better select the optimal drug target is to generate unbiased mass-spectrometry based proteomic data from the circulating tumor cells (CTCs) isolated from blood. In this study, we collaborated with Astrin Biosciences using their patented isolation technology to enrich CTCs with high purity from the blood of 57 metastatic castration resistant prostate cancer (mCRPC) patients. The CTC-enriched sample (along with a patient-matched control sample consisting primarily of white blood cells) was analyzed in real time for either PSMA protein (Lutetium-PSMA-617 study, n=32) or via mass-spectrometry (CTC proteomics study, n=25). Over 1,500 peptides corresponding to greater than 600 proteins were identified from each patient’s CTCs. These included increased epithelial cell markers in the CTC-enriched sample and increased WBC markers in the control sample. Specifically, detection of the androgen receptor protein was identified in the CTC-enriched sample which is of particular interest in mCRPC patients. Furthermore, this method is able to detect and quantify PSMA expression, which is of clear relevance in the context of PSMA-directed therapeutics. This study demonstrates the feasibility of obtaining large scale proteomic data from a liquid biopsy. Future studies will focus on cancer signaling mechanisms and biomarkers to elucidate the clinical utility of such data. As more patients are analyzed, we will compare proteomic data with known tissue proteome information when available and to correlate these with drug response to improve treatment selection and patient outcomes. Citation Format: Justin M. Drake, Ali Arafa, Alec Horrmann, Kaylee J. Kamalanathan, Catalina Galeano-Garces, Zoi Sychev, Nicholas Heller, Mahdi Ahmadi, Megan Ludwig, Olivia Hedeen, Alexa Hesch, Grant Schaap, Joel Hapke, Jeff Miller, Ivo Babris, Tuan Lee, Tony Clacko, Justin Hwang, Jiarong Hong, Badri Konety, Jayant Parthasarathy, Emmanuel Antonarakis. PSMA-based detection and global proteome-based analysis of circulating tumor cells in castration resistant prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6563.

Current Methods for Analysing Mesenchymal Stem Cell-Derived Extracellular Vesicles.

The use of extracellular vesicles (EVs) generated by mesenchymal stem cells (MSCs) holds great promise as a novel therapeutic approach. Although their immunomodulatory and regeneration potential has been reported to be similar to that of MSCs, the use of MSC-derived EVs in clinical settings will require several problems to be resolved. It is necessary to develop a standardised and widely accepted isolation technology and to improve methods such as the quantification and characterisation of MSC-derived EVs. In this way, EV studies can be compared, the acquired knowledge can be safely transferred to clinical platforms and the clinical results can be evaluated appropriately. There are many procedures for the collection and analysis of vesicles derived from different cells; however, this review provides an overview of methods for the determination of the total protein amount, specific proteins, particle number, non-protein markers like lipids and RNA, microscopy and other methods focusing on MSC-derived EVs.

Seismic isolation technology of shallow buried large section utility tunnel with soft soils in seismically vulnerable area

Shallow utility tunnels with exceptionally large cross-sections in weak soil can face significantly more severe seismic risks compared to conventional deep tunnels in seismic hazard areas. This study investigates the seismic response and isolation technologies applied to a large section utility tunnel with 4 compartments in one layer, employing seismic simulations. The engineering context, dynamic motions, and measuring points of the numerical simulation were introduced. Subsequently, the finite element method was employed to explore the seismic behaviors of the large section utility tunnel when subjected to strong earthquake excitations under four conditions. The study explored and comparatively evaluated the seismic isolation effectiveness of three proposed schemes: the grouting scheme, the buffer layer, and the assembly of three-quarters buffer layer, cushion and grouting. The analysis included various indexes such as the deformation, the principal and shear stress, and the safety factor. The finding reveals that the assembly seismic scheme exhibits the most significant seismic effect (95.39%), followed by the buffer layer (38.82%), and the grouting scheme (25.66%). The assembly seismic scheme is recommended for the seismic design in the current large-section utility tunnels. These conclusions provide valuable scientific guidance for the seismic design of large-section utility tunnels, aiding in enhancing earthquake resilience.

Fuzzy algorithm-based active control method for vibration of a mechanical gear transmission system

The detached raft automatic frequency isolation system is a complicated system with high exceptionally nonlinear, high electromagnetic, and multi-source vibration modes. However, it generates a statistical method and it is hard to operate the organization. The fuzzy control algorithm, as an astute control method, can give a keen path to the active management of a complicated system of floating rafts. This study uses a system identification approach to construct mathematical models for a floating raft active vibration isolation system with discrete transfer work. The fuzzy model is used in tests and simulations controller is built using two contributions of acceleration and its variation, as well as a single result of control voltage. The control isolation system is a complicated system with many moving parts. A lot of moving parts profoundly nonlinear, high electromagnetic and multi-source vibration modes, generating a statistical method and it is hard to operate the organization. The fuzzy control algorithm, as a smart control method, can give a keen path to the active management of a sophisticated floating raft system. This research uses an identification strategy to construct a floating raft active vibration isolation technology discrete transfer work mathematical models. The fuzzy controller is then put together using two contributions: acceleration and variation, as well as a single outcome of control voltage for simulations and experiments research.

Design and Experimental Study of a Hybrid Micro-Vibration Isolation System Based on a Strain Sensor for High-Precision Space Payloads.

Micro-vibrations significantly influence the imaging quality and pointing accuracy of high-precision space-borne payloads. To mitigate this issue, vibration isolation technology must be employed to reduce the transmission of micro-vibrations to payloads. In this paper, a novel active-passive hybrid isolation (APHI) system based on a strain sensor is proposed for high-precision space payloads, and corresponding theoretical and experimental studies are implemented. First, a theoretical analysis model of the APHI system is established using a two-degrees-of-freedom system, and an integral control method based on strain sensing is presented. Then, an electromagnetic damper, active piezoelectric actuator, and strain sensor are designed and manufactured. Finally, an APHI experimental system is implemented to validate the effectiveness of electromagnetic damping and strain-sensing active control. Additionally, the control effects of acceleration, displacement, and strain sensors are compared. The results demonstrate that strain sensors can achieve effective active damping control, and the control method based on strain sensors can effectively suppress the payload response while maintaining stability. Both displacement and strain sensors exhibit superior suppression effects compared with the acceleration sensor, with the strain sensor showing greater potential for practical engineering applications than the displacement sensor.

A novel three-dimensional isolation bearing for buildings subject to metro- and earthquake-induced vibrations: Laboratory test and application

The implementation of three-dimensional (3D) isolation technology effectively enhances the structural seismic resilience and mitigates the impact of vibrations induced by metro trains. However, the challenge remains to increase the vertical loading capacity of 3D isolation bearings while reducing their vertical stiffness and guaranteeing excellent stability. The 3D isolation bearing (3DIB) consisting of an improved laminated natural rubber bearing (LNR-400-imp) and spring bearings (SBs) built vertically in series were proposed in this study. Its design principle and working mechanism were introduced, and prototype specimens were designed and manufactured. The 3D mechanical performance of the 3DIB was investigated through horizontal and vertical tests. Furthermore, the earthquake and metro vibration isolation performances of the building installed with the 3DIB were analyzed using a case study. The results demonstrated that the 3DIB exhibited horizontal energy dissipation effect, and had stable vertical performance, higher vertical loading capacity, and lower vertical stiffness attributing to the improved LNR-400-imp and SBs. Specifically, the vertical stiffness of the 3DIB was about 1/14 of that of the traditional LNR-400-tra. The case study demonstrated that the 3DIB had remarkable earthquake and metro vibration isolation effects, behaving huge potentials in enhancing the seismic resilience of structures and mitigating the impact of metro vibrations. This study offers valuable insight and practical guidance for future research on 3DIB in the field of vibration isolation, contributing to the advancement of 3D isolation technology.

A novel active and passive integrated vibration isolator based on piezoelectric stack: Characteristic analysis and experimental investigation

Passive vibration isolation has the advantages of simple structure, high reliability, and strong ability to absorb high-frequency vibration. Active vibration isolation has wide application range, strong controllability, and good vibration suppression effect for specific frequency band. Active and passive integrated vibration isolation technology combines the characteristics of both and has obvious advantages in dealing with the complex vibration environment in modern engineering practice. In this work, piezoelectric stack actuator is selected as the active control output source and vulcanized butyl rubber is used as the passive vibration absorber. The dynamic model of the novel active and passive integrated isolator is established, then the effects of different parameters on its vibration transmission performance are studied. Furthermore, a typical two-degree-of-freedom vibration isolation system model is established. By comparing the change of vibration transmissibility under different feedback forms, the design of the feedforward–feedback composite controller is applied. Finally, a double-layer vibration isolation test platform is built to verify the vibration reduction capability of the active and passive integrated isolator. The experimental results show that both the passive vibration absorption and active vibration suppression functions of this novel vibration isolator are particularly effective.

Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Due to the insidious onset and rapid progression and a lack of effective treatments, the prognosis of patients with HCC is extremely poor, with the average 5-year survival rate being less than 10%. The tumor microenvironment (TME), the internal environment in which HCC develops, can regulate the oncogenesis, development, invasion, and metastasis of HCC. During the process of cancer progression, HCC cells can regulate the biological behaviors of tumor cells, cancer-associated fibroblasts, cancer-associated immune cells, and other cells in the TME by releasing exosomes containing specific signals, thereby promoting cancer progression. However, the exact molecular mechanisms and the roles of exosomes in the specific cellular regulation of these processes are not fully understood. Herein, we summarized the TME components of HCC, the sources and the biological traits of exosomes in the TME, and the impact of mechanical factors on exosomes. In addition, special attention was given to the discussion of the effects of HCC-exosomes on different types of cells in the microenvironment. There are still many difficulties to be overcome before exosomes can be applied as carriers in clinical cancer treatment. First of all, the homogeneity of exosomes is difficult to ensure. Secondly, exosomes are mainly administered through subcutaneous injection. Although this method is simple and easy to implement, the absorption efficiency is not ideal. Thirdly, exosome extraction methods are limited in number and inefficient, making it difficult to prepare exosomes in large quantities. It is important to ensure that exosomes are used in sufficient quantities to trigger an effective tumor immune response, especially for exosome-mediated tumor immunotherapy. With the improvement in identification, isolation, and purification technology, exosomes are expected to be successfully used in the clinical diagnosis of early-stage HCC and the clinical treatment of liver cancer.

Displacement‐based design procedures for rigid block isolation

AbstractWhen subjected to earthquakes, many objects or structural elements behave like rocking rigid blocks. Computer servers, medical shelves, art objects, statues, and electrical transformers are frequently included in this category. Protection of these objects is an important task, considering that their value could be inestimable or their operation crucial during earthquakes; base isolation technology has been proven to be a viable option for this purpose. Initially, the dynamic model of a rocking rigid block placed on a base isolation device is reviewed. Then, two equivalent‐static displacement‐based procedures for designing the isolators for these types of objects are proposed, and the main steps are illustrated. The first procedure aims to determine isolator characteristics to prevent the initiation of rocking motion during the code‐level earthquake event. The second procedure is aimed at designing isolators that allow a specified maximum rotation of the block during seismic events. The proposed procedures are validated by means of time‐history analyses for a suite of spectrum‐compatible accelerograms. The first displacement‐based procedure appears particularly suitable for objects of small to medium size. The validation of the second procedure demonstrates that the equal displacement rule can be applied for this kind of systems, despite their softening. The results also indicate that the approach is particularly effective for medium to large structures/objects, if small oscillations are acceptable. The controlled rocking procedure offers a significant advantage by allowing for a reduction in the maximum displacement and period of the isolator, compared to situations where rocking motion must be prevented entirely.

Design and optimization of H-type asymmetric magnetic suspension vibration absorber for ships

The active–passive hybrid vibration isolation technology emerges with the advancement of the requirements for ship vibration and noise reduction. Among these, the magnetic suspension damper based on magnetic suspension technology has received more attention. In this paper, the effects of magnetic pole area and control current on the magnetic flux density and suspension force are verified by establishing a magnetic suspension structure model and comparing and verifying the results carried out by combining the theoretical formulas and finite element simulation. By exploring the effect of the structure on the magnetic flux density and suspension force, a new H-type asymmetric magnetic suspension structure is proposed and simulated. The results show that the H-type asymmetric magnetic suspension structure is more successful at improving the suspension force while also widening the suspension force response interval and improving the performance of the magnetic suspension damper. In addition to offering a new design concept for the construction of ship vibration and noise reduction structures, this structural solution serves as a reference for the development of magnetic suspension dampers.

Review of Lightweight Vibration Isolation Technologies for Marine Power Devices

Vibration induced by marine power devices (MPD) transmitting to the hull structure is one of the most important factors that cause ship vibration and underwater sound radiation. Vibration isolation technologies (VIT) are widely applied to reduce the vibration transmission. However, the overweight issue of VIT for marine power devices is a currently challenging engineering problem. The current reserve of lightweight and high-efficiency VIT for MPD and relevant theoretical and design research are seriously insufficient. This article first elaborates the causes of the overweight problem of VIT for MPD: (1) failing to grasp the quantitative law; (2) single vibration suppression mechanism. Then, it systematically sorts out the technical methods and application examples with potential to solve the overweight problem, such as dynamic optimization design, lightweight material method, novel intermediate mass structures, distributed dynamic vibration absorbers (DDVAs), locally resonant structures (LRS), particle damping (PD), quasizero stiffness isolators (QZSI), and active vibration control (AVC) technologies. Finally, the future development of lightweight VIT for MPD is prospected. It can be used as a reference for marine vessel vibration attenuation research and engineering design.

Input Energy Reduction‐Oriented Control and Analytical Design of Inerter‐Enabled Isolators for Large‐Span Structures

Seismic isolation technologies for large‐span structures have rapidly developed alongside the popularization of the seismic resilience concept. To produce a high‐efficiency isolation technology with lower energy dissipation demands, this paper proposes a novel inerter‐enabled isolator (IeI) and a tailored input energy reduction‐oriented design method. The inerter‐based damper within the IeI is developed by combining the dashpot, tuning spring, and two inerters to facilitate the optimization of inerter distribution. Assuming the large‐span structure remains linear, the overall seismic input energy of the large‐span structure with IeIs and its allocation in the superstructure and additional damping are quantified using stochastic energy analysis. The advantages of the IeI over the conventional linear viscous damper (LVD) isolator are elucidated through dimensionless parametric analysis. Based on the results of parametric analysis, an input energy reduction‐oriented design method is proposed for the IeI, along with an easy‐to‐follow diagram that helps with preliminary design in practical applications. The effectiveness of the IeI and the proposed design method is validated through a design case study of a benchmark large‐span structure. The results demonstrate that the IeI reduces the seismic response of large‐span structures by simultaneously employing the input energy reduction effect of grounded inerters with the damping‐enhancing effect of inerter‐based dampers. The proposed design method effectively balances the performance of controlling the large‐span structure and the isolator displacement. Under consistent control performance and isolator displacement constraints, the IeI requires much less damping coefficient and energy dissipation capacity than the conventional LVD isolator. Moreover, leveraging the damping enhancement and input energy reduction effects, the IeI achieves comparable control performance to the conventional LVD isolator, even under stricter isolator displacement constraints.

Compressed fluid-based technology for downstream isolation of bluish anthocyanin-derived pigments obtained from blueberry surplus.

A dynamic compressed fluid-based separation process combining carbon dioxide and ethanol was explored to isolate portisins previously hemi-synthesized from blueberry surplus anthocyanins. The influence of process parameters such as pressure (100-500 bar), temperature (40-60 °C), and ethanol content in the compressed fluid mixture (20-50 wt%) on extraction yield, portisins yield, and portisins content in the extract was investigated. The two-step isolation process includes (1) a first step at 100 bar, 60 °C, and 20 wt% ethanol content in the compressed fluid mixture to remove the low polarity compounds; and (2) a second step at 500 bar, 40 °C, and 100 wt% ethanol to recover portisins, resulting in a 1.5-fold increase in portisins content. The performance of the two-step separation process was compared to centrifugal partitional chromatography and conventional reverse phase liquid chromatography already reported in terms of portisins content in the extract, process throughput, process efficiency, and total solvent used. The two-step separation process decreased the total solvent used, although with a decrease in the throughput and efficiency. Nevertheless, the choice of the best separation technology depends on the application, as these techniques result in different portisins purities. Overall, this study contributed to a scalable and more sustainable process for natural colorant production, specifically focusing on blue pigments, with several industrial applications.