Future of Digital Assays to Resolve Clinical Heterogeneity of Single Extracellular Vesicles

Morales, Renee Tyler Tan; Ko, Jina

doi:10.1021/acsnano.2c04337

Cited by 46 publications

(68 citation statements)

References 284 publications

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“…The development of TENPO to isolate EV subpopulations from clinical specimens offers new opportunities in biomarker development and understanding EV biology. As EV-based diagnostics move towards clinical application, the literature has shown how EV heterogeneity drives cancer biology [34], in uences diagnostics [35][36], and modulates cargoes in different EV types [37]. Using immunomagnetic isolation via speci c surface markers, TENPO can take advantage of EV heterogeneity by sorting distinct EV subpopulations from a single patient sample.…”

Section: Discussionmentioning

confidence: 99%

Parallelized immunomagnetic nanopore sorting: modeling, scaling, and optimization of surface marker specific isolation of extracellular vesicles from complex media

Lin

Shen

Spychalski

et al. 2023

Preprint

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The isolation of specific subpopulations of extracellular vesicles (EVs) based on their expression of surface markers poses a significant challenge due to their nanoscale size (< 800 nm), their heterogeneous surface marker expression, and the vast number of background EVs present in clinical specimens (1010-1012 EVs/mL in blood). Highly parallelized nanomagnetic sorting using track etched magnetic nanopore (TENPO) chips has achieved precise immunospecific sorting with high throughput and resilience to clogging. However, there has not yet been a systematic study of the design parameters that control the trade-offs in throughput, target EV recovery, and specificity in this approach. We combine finite-element simulation and experimental characterization of TENPO chips to elucidate design rules to isolate EV subpopulations from blood. We demonstrate the utility of this approach by increasing specificity > 10x relative to prior published designs without sacrificing recovery of the target EVs by selecting pore diameter, number of membranes placed in series, and flow rate. We compare TENPO-isolated EVs to those of gold-standard methods of EV isolation and demonstrate its utility for wide application and modularity by targeting subpopulations of EVs from multiple models of disease including lung cancer, pancreatic cancer, and liver cancer.

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Section: Discussionmentioning

confidence: 99%

Parallelized immunomagnetic nanopore sorting: modeling, scaling, and optimization of surface marker specific isolation of extracellular vesicles from complex media

Lin

Shen

Spychalski

et al. 2023

Preprint

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“…Moreover, the clinical practice of EVs is challenged by their heterogeneity to some extent. Optimization of current digital assays has been proposed to do single-vesicle-resolution studies, especially during the clinical analysis of liquid biopsies ( 215 ). Immune biocompatibility of EVs is the other criterion to be investigated in autoimmune diseases.…”

Section: Msc-evs Vs Mscs: Open Issuesmentioning

confidence: 99%

“…EVs were reported to demonstrate cell and tissue-specific autonomous targeting capabilities ( 139 , 215 ). The interactions between EVs and the neighboring or distant acceptor cells occur through diverse mechanisms.…”

Section: Msc-evs Vs Mscs: Open Issuesmentioning

confidence: 99%

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

et al. 2023

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The conventional therapeutic approaches to treat autoimmune diseases through suppressing the immune system, such as steroidal and non-steroidal anti-inflammatory drugs, are not adequately practical. Moreover, these regimens are associated with considerable complications. Designing tolerogenic therapeutic strategies based on stem cells, immune cells, and their extracellular vesicles (EVs) seems to open a promising path to managing autoimmune diseases’ vast burden. Mesenchymal stem/stromal cells (MSCs), dendritic cells, and regulatory T cells (Tregs) are the main cell types applied to restore a tolerogenic immune status; MSCs play a more beneficial role due to their amenable properties and extensive cross-talks with different immune cells. With existing concerns about the employment of cells, new cell-free therapeutic paradigms, such as EV-based therapies, are gaining attention in this field. Additionally, EVs’ unique properties have made them to be known as smart immunomodulators and are considered as a potential substitute for cell therapy. This review provides an overview of the advantages and disadvantages of cell-based and EV-based methods for treating autoimmune diseases. The study also presents an outlook on the future of EVs to be implemented in clinics for autoimmune patients.

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“…Then signals are amplified by chemical or enzymatic reactions and reported via fluorescence within each complex. [237,238] Digital assays characterize single EVs with higher accuracy than analog measurements. Two DMF for single EV characterization will be discussed in this article, including dELISA and dPCR.…”

Section: Digital-based Technologymentioning

confidence: 99%

From Conventional to Microfluidic: Progress in Extracellular Vesicle Separation and Individual Characterization

Chen

Lin

Cheng

et al. 2023

Adv Healthcare Materials

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Extracellular vesicles (EVs) are nanoscale membrane vesicles, which contain a wide variety of cargo such as proteins, miRNAs, and lipids. A growing body of evidence suggests that EVs are promising biomarkers for disease diagnosis and therapeutic strategies. Although the excellent clinical value, their use in personalized healthcare practice is not yet feasible due to their highly heterogeneous nature. Taking the difficulty of isolation and the small size of EVs into account, the characterization of EVs at a single‐particle level is both imperative and challenging. In a bid to address this critical point, more research has been directed into a microfluidic platform because of its inherent advantages in sensitivity, specificity, and throughput. This review discusses the biogenesis and heterogeneity of EVs and takes a broad view of state‐of‐the‐art advances in microfluidics‐based EV research, including not only EV separation, but also the single EV characterization of biophysical detection and biochemical analysis. To highlight the advantages of microfluidic techniques, conventional technologies are included for comparison. The current status of artificial intelligence (AI) for single EV characterization is then presented. Furthermore, the challenges and prospects of microfluidics and its combination with AI applications in single EV characterization are also discussed. In the foreseeable future, recent breakthroughs in microfluidic platforms are expected to pave the way for single EV analysis and improve applications for precision medicine.

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Future of Digital Assays to Resolve Clinical Heterogeneity of Single Extracellular Vesicles

Cited by 46 publications

References 284 publications

Parallelized immunomagnetic nanopore sorting: modeling, scaling, and optimization of surface marker specific isolation of extracellular vesicles from complex media

Parallelized immunomagnetic nanopore sorting: modeling, scaling, and optimization of surface marker specific isolation of extracellular vesicles from complex media

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

From Conventional to Microfluidic: Progress in Extracellular Vesicle Separation and Individual Characterization

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