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1. Recent progress in microRNA detection using integrated electric fields and optical detection methods

   https://doi.org/10.3389/frlct.2024.1349384  

   Velmanickam, Logeeshan; Nawarathna, Dharmakeerthi (April 2024, Frontiers in Lab on a Chip Technologies)

   Low-cost, highly-sensitivity, and minimally invasive tests for the detection and monitoring of life-threatening diseases and disorders can reduce the worldwide disease burden. Despite a number of interdisciplinary research efforts, there are still challenges remaining to be addressed, so clinically significant amounts of relevant biomarkers in body fluids can be detected with low assay cost, high sensitivity, and speed at point-of-care settings. Although the conventional proteomic technologies have shown promise, their ability to detect all levels of disease progression from early to advanced stages is limited to a limited number of diseases. One potential avenue for early diagnosis is microRNA (miRNA). Due to their upstream positions in regulatory cascades, blood-based miRNAs are sensitive biomarkers that are detectable earlier than those targeted by other methods. Therefore, miRNA is a promising diagnostic biomarker for many diseases, including those lacking optimal diagnostic tools. Electric fields have been utilized to develop various biomedical assays including cell separation, molecules detection and analysis. Recently, there has been a great interest in the utility of electric fields with optical detection methods, including fluorescence and surface plasmons toward biomarker detection. This mini review first summarizes the recent development of miRNA as a biomarker. Second, the utility of electric fields and their integration with fluorescence detection methods will be discussed. Next, recent studies that utilized electric fields and optical detection methods will be discussed. Finally, in conclusion, technology gaps and improvements needed to enable low-cost and sensitive biomarker detection in point-of-care settings will be discussed. 

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2. Point‐of‐critical‐care diagnostics for sepsis enabled by multiplexed micro and nano sensing technologies

   https://doi.org/10.1002/wnan.1701  

   Ashley, Brandon K.; Hassan, Umer (March 2021, WIREs Nanomedicine and Nanobiotechnology)

   Abstract Sepsis is responsible for the highest economic and mortality burden in critical care settings around the world, prompting the World Health Organization in 2018 to designate it as a global health priority. Despite its high universal prevalence and mortality rate, a disproportionately low amount of sponsored research funding is directed toward diagnosis and treatment of sepsis, when early treatment has been shown to significantly improve survival. Additionally, current technologies and methods are inadequate to provide an accurate and timely diagnosis of septic patients in multiple clinical environments. For improved patient outcomes, a comprehensive immunological evaluation is critical which is comprised of both traditional testing and quantifying recently proposed biomarkers for sepsis. There is an urgent need to develop novel point‐of‐care, low‐cost systems which can accurately stratify patients. These point‐of‐critical‐care sensors should adopt a multiplexed approach utilizing multimodal sensing for heterogenous biomarker detection. For effective multiplexing, the sensors must satisfy criteria including rapid sample to result delivery, low sample volumes for clinical sample sparring, and reduced costs per test. A compendium of currently developed multiplexed micro and nano (M/N)‐based diagnostic technologies for potential applications toward sepsis are presented. We have also explored the various biomarkers targeted for sepsis including immune cell morphology changes, circulating proteins, small molecules, and presence of infectious pathogens. An overview of different M/N detection mechanisms are also provided, along with recent advances in related nanotechnologies which have shown improved patient outcomes and perspectives on what future successful technologies may encompass. This article is categorized under:Diagnostic Tools > Biosensing 

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3. One locus with two roles: microRNA‐independent functions of microRNA‐host‐gene locus‐encoded long noncoding RNAs

   https://doi.org/10.1002/wrna.1625  

   Sun, Qinyu; Song, You Jin; Prasanth, Kannanganattu V. (September 2020, WIREs RNA)

   Abstract Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that do not code for proteins. LncRNAs play crucial regulatory roles in several biological processes via diverse mechanisms and their aberrant expression is associated with various diseases. LncRNA genes are further subcategorized based on their relative organization in the genome. MicroRNA (miRNA)‐host‐gene‐derived lncRNAs (lnc‐MIRHGs) refer to lncRNAs whose genes also harbor miRNAs. There exists crosstalk between the processing of lnc‐MIRHGs and the biogenesis of the encoded miRNAs. Although the functions of the encoded miRNAs are usually well understood, whether those lnc‐MIRHGs play independent functions are not fully elucidated. Here, we review our current understanding of lnc‐MIRHGs, including their biogenesis, function, and mechanism of action, with a focus on discussing the miRNA‐independent functions of lnc‐MIRHGs, including their involvement in cancer. Our current understanding of lnc‐MIRHGsstrongly indicates that this class of lncRNAs could play important roles in basic cellular events as well as in diseases. This article is categorized under:Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAsRegulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs 

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4. Integration of chemically modified nucleotides with DNA strand displacement reactions for applications in living systems

   https://doi.org/10.1002/wnan.1743  

   Kabza, Adam M.; Kundu, Nandini; Zhong, Wenrui; Sczepanski, Jonathan T. (July 2021, WIREs Nanomedicine and Nanobiotechnology)

   Abstract Watson–Crick base pairing rules provide a powerful approach for engineering DNA‐based nanodevices with programmable and predictable behaviors. In particular, DNA strand displacement reactions have enabled the development of an impressive repertoire of molecular devices with complex functionalities. By relying on DNA to function, dynamic strand displacement devices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation in living systems has been a slow process due to several persistent challenges, including nuclease degradation. To circumvent these issues, researchers are increasingly turning to chemically modified nucleotides as a means to increase device performance and reliability within harsh biological environments. In this review, we summarize recent progress toward the integration of chemically modified nucleotides with DNA strand displacement reactions, highlighting key successes in the development of robust systems and devices that operate in living cells and in vivo. We discuss the advantages and disadvantages of commonly employed modifications as they pertain to DNA strand displacement, as well as considerations that must be taken into account when applying modified oligonucleotide to living cells. Finally, we explore how chemically modified nucleotides fit into the broader goal of bringing dynamic DNA nanotechnology into the cell, and the challenges that remain. This article is categorized under:Diagnostic Tools > In Vivo Nanodiagnostics and ImagingNanotechnology Approaches to Biology > Nanoscale Systems in BiologyDiagnostic Tools > Biosensing 

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5. Development of a Microfluidic Device for Exosome Isolation in Point-of-Care Settings

   https://doi.org/10.3390/s23198292  

   Ramnauth, Natasha; Neubarth, Elise; Makler-Disatham, Amy; Sher, Mazhar; Soini, Steven; Merk, Vivian; Asghar, Waseem (October 2023, Sensors)

   Exosomes have gained recognition in cancer diagnostics and therapeutics. However, most exosome isolation methods are time-consuming, costly, and require bulky equipment, rendering them unsuitable for point-of-care (POC) settings. Microfluidics can be the key to solving these challenges. Here, we present a double filtration microfluidic device that can rapidly isolate exosomes via size-exclusion principles in POC settings. The device can efficiently isolate exosomes from 50–100 µL of plasma within 50 min. The device was compared against an already established exosome isolation method, polyethylene glycol (PEG)-based precipitation. The findings showed that both methods yield comparable exosome sizes and purity; however, exosomes isolated from the device exhibited an earlier miRNA detection compared to exosomes obtained from the PEG-based isolation. A comparative analysis of exosomes collected from membrane filters with 15 nm and 30 nm pore sizes showed a similarity in exosome size and miRNA detection, with significantly increased sample purity. Finally, TEM images were taken to analyze how the developed devices and PEG-based isolation alter exosome morphology and to analyze exosome sizes. This developed microfluidic device is cost-efficient and time-efficient. Thus, it is ideal for use in low-resourced and POC settings to aid in cancer and disease diagnostics and therapeutics. 

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