Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Enhanced Point of Use Filtration for Cleaning without Small Particle Addition

Strict semiconductor cleaning demands for shrinking feature size and increased contamination sensitivity have led to projects that improve performance. The sources of contamination are generally the process chemicals themselves, where wafers are exposed to chemicals for etching or cleaning. Concerns over contamination are compounded in wet benches where chemical baths are re-circulated for periods up to 24 hours. Particle and metal impurities can arise from insufficiently pure chemicals/water, or liquid carry contaminants to the tools through plumbing components such as valves and pumps, and chemical containers/lines. Strict chemical, deionized water (DIW) and material specifications have benefited the industry. Currently, typical purity levels are below detection limits. That being said, point of use filtration offers enhanced reduction of contamination for critical cleans. In this paper we investigate particle adsorption on an immersed wafer surface in dilute HF and rinse applications. Particle addition for various immersion times in the tank can probe the contamination concentration in a solution. In this study, point of use filtration with tighter retention rating and cleaner devices is demonstrated to be critical for small particle control. 300mm wafers were processed by immersing a batch of up to 50 at a time in dilute HF and oxidizing agents for several minutes, rinsing and then drying. Inspection was conducted on a Surfscan SP3 system by KLA-Tencor. As shown below, the surface count of defects increases linearly with immersion time in HF for wafers processed normally. This demonstrates that particle contamination is present in the tank. Due to its acidic and etching nature (impact on particle zeta potential and silica concentration), HF processing is difficult in semiconductor processing.  There is a need for enhanced particle retention filters with adequate flow rate to remove undesirable particles. The team evaluated tighter and cleaner Torrento® filters.  Torrento® devices are polytetrafluoroethylene membrane filters that deliver contaminant protection performance for critical wet etch and cleaning technology. In a wafer manufacturing facility, recirculation filters were upgraded in a dilute HF tank. Tighter and cleaner Torrento® devices replaced the previous filters.  Greater than one month of sampling was conducted, before and after the exchange. SP3 data for 32nm particles show that the average decreases &gt;35%, and the standard deviation is reduced as well. Surface metals by VPD-ICPMS confirm no adverse effects. Separately, deionized water point of use purifier + filters were upgraded. Tighter retention Protego devices replaced the previously used purifiers.  Protego® Plus ion-exchange purifier + filters are designed to reduce particles and metallic contamination during rinse. The Protego Plus technology is capable of processing DI water applications up to 80°C. Greater than one month of sampling was conducted, before and after the exchange. SP3 data for 26nm particles demonstrate that the average is reduced by &gt;30%, and the standard deviation is lowered in turn. Surface metals by VPD-ICPMS show improvement (e.g. reduction in Na). Particle performance of acidic baths and DIW rinses has been shown to depend strongly on point of use filtration. Systematic studies of immersion time and large quantities of wafer production data are required to isolate the contribution and measure improvements. Figure 1 <jats:p /

Enhanced Point of Use Filtration for Cleaning without Small Particle Addition

Enhanced liquid filtration for critical cleans is essential for particle and contamination reduction. Tighter and cleaner base membranes offer a path for reduced defect adders. Particle adsorption is investigated on an immersed wafer surface in dilute HF and rinse applications. Systematic studies of immersion time, bath life and high volume wafer production data are required to isolate the particle contribution and quantify process improvements. Wet particle defectivity of a cleaning process was evaluated before and after filter installation. Little difference in filter performance is observed at &gt;37 nm, while clear improvements are found at smaller bin sizes &lt;37 nm. Point of use filtration with increased retention efficiency translates into better performance, especially for very small particles. </jats:p