Glucose, as an essential substance directly involved in metabolic processes, is closely related to the occurrence of various diseases such as glucose metabolism disorders and islet cell carcinoma. ...Therefore, it is crucial to develop sensitive, accurate, rapid, and cost effective methods for frequent and convenient detections of glucose. Microfluidic Paper-based Analytical Devices (μPADs) not only satisfying the above requirements but also occupying the advantages of portability and minimal sample consumption, have exhibited great potential in the field of glucose detection. This article reviews and summarizes the most recent improvements in glucose detection in two aspects of colorimetric and electrochemical μPADs. The progressive techniques for fabricating channels on μPADs are also emphasized in this article. With the growth of diabetes and other glucose indication diseases in the underdeveloped and developing countries, low-cost and reliably commercial μPADs for glucose detection will be in unprecedentedly demand.
Recent reports have indicated that aberrant expression of microRNAs is highly correlated with occurrence of lung cancer. Therefore, highly sensitive detection of lung cancer specific microRNAs ...provides an attractive approach in lung cancer early diagnostics. Herein, we designed 3D DNA origami structure that enables electrochemical detection of lung cancer related microRNAs. The 3D DNA origami structure is constituted of a ferrocene-tagged DNA of stem-loop structure combined with a thiolated tetrahedron DNA nanostructure at the bottom. The top portion hybridized with the lung cancer correlated microRNA, while the bottom portion was self-assembled on gold disk electrode surface, which was modified with gold nanoparticles (Au NPs) and blocked with mercaptoethanol (MCH). The preparation process and the performance of the proposed electrochemical genosensor were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Under the optimal conditions, the developed genosensor had a detection limit of 10pM and a good linearity with microRNA concentration ranging from 100pM to 1µM, which showed a great potential in highly sensitive clinical cancer diagnosis application.
•A “signal-on” electrochemical genosensor based on stem-loop DNA probe was proposed.•2D stem-loop DNA structure was combined with 3D DNA origami as the sensing probe.•Detection signals showed linearity with microRNA concentrations from 100pM to 1µM.•The developed genosensor had a detection limit of 10pM.•The genosensor can be used in simulative cellular environment.
Profiling protein expression at single‐cell resolution is essential for fundamental biological research (such as cell differentiation and tumor microenvironmental examination) and clinical precision ...medicine where only a limited number of primary cells are permitted. With the recent advances in engineering, chemistry, and biology, single‐cell protein analysis methods are developed rapidly, which enable high‐throughput and multiplexed protein measurements in thousands of individual cells. In combination with single cell RNA sequencing and mass spectrometry, single‐cell multi‐omics analysis can simultaneously measure multiple modalities including mRNAs, proteins, and metabolites in single cells, and obtain a more comprehensive exploration of cellular signaling processes, such as DNA modifications, chromatin accessibility, protein abundance, and gene perturbation. Here, the recent progress and applications of single‐cell protein analysis technologies in the last decade are summarized. Current limitations, challenges, and possible future directions in this field are also discussed.
In this review, recent progress and applications of single‐cell protein analysis technologies are summarized. The principles, characteristics, and applications of the emerging single‐cell multi‐omics analysis techniques are also introduced. In addition, current limitations and future prospects of single‐cell protein analysis are discussed.
With the expanding applications of mass cytometry in medical research, a wide variety of clustering methods, both semi-supervised and unsupervised, have been developed for data analysis. Selecting ...the optimal clustering method can accelerate the identification of meaningful cell populations.
To address this issue, we compared three classes of performance measures, "precision" as external evaluation, "coherence" as internal evaluation, and stability, of nine methods based on six independent benchmark datasets. Seven unsupervised methods (Accense, Xshift, PhenoGraph, FlowSOM, flowMeans, DEPECHE, and kmeans) and two semi-supervised methods (Automated Cell-type Discovery and Classification and linear discriminant analysis (LDA)) are tested on six mass cytometry datasets. We compute and compare all defined performance measures against random subsampling, varying sample sizes, and the number of clusters for each method. LDA reproduces the manual labels most precisely but does not rank top in internal evaluation. PhenoGraph and FlowSOM perform better than other unsupervised tools in precision, coherence, and stability. PhenoGraph and Xshift are more robust when detecting refined sub-clusters, whereas DEPECHE and FlowSOM tend to group similar clusters into meta-clusters. The performances of PhenoGraph, Xshift, and flowMeans are impacted by increased sample size, but FlowSOM is relatively stable as sample size increases.
All the evaluations including precision, coherence, stability, and clustering resolution should be taken into synthetic consideration when choosing an appropriate tool for cytometry data analysis. Thus, we provide decision guidelines based on these characteristics for the general reader to more easily choose the most suitable clustering tools.
With ever increasing drug resistance and emergence of new diseases, demand for new drug development is at an unprecedented urgency. This fact has led to extensive recent efforts to develop new drugs ...and novel techniques for efficient drug screening. However, new drug development is commonly hindered by cost and time span. Thus, developing more accessible, cost-effective methods for drug screening is necessary. Compared with conventional drug screening methods, a microfluidic-based system has superior advantages in sample consumption, reaction time, and cost of the operation. In this paper, the advantages of microfluidic technology in drug screening as well as the critical factors for device design are described. The strategies and applications of microfluidics for drug screening are reviewed. Moreover, current limitations and future prospects for a drug screening microdevice are also discussed.
Breast cancer is among the most common malignant tumors. It is the second leading cause of cancer mortality among women in the United States. Curcumin, an active derivative from turmeric, has been ...reported to have anticancer and chemoprevention effects on breast cancer. Curcumin exerts its anticancer effect through a complicated molecular signaling network, involving proliferation, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) pathways. Experimental evidence has shown that curcumin also regulates apoptosis and cell phase-related genes and microRNA in breast cancer cells. Herein, we review the recent research efforts in understanding the molecular targets and anticancer mechanisms of curcumin in breast cancer.
Cell heterogeneity exists among different tissues, even in the same type of cells. Cell heterogeneity leads to a difference in cell size, functions, biological activity, and for cancer cells it ...causes different drug responses and resistance. Meanwhile, microfluidics is a promising tool for single-cell research to reveal cell heterogeneity.
Through literature research conducted over the past ten years on microfluidics, we summarize and introduce the application of microfluidics in single-cell separation and manipulation, featuring techniques, such as acoustic manipulation, optical manipulation, single-cell trapping, and patterning, as well as single-cell omics including singlecell genomics, single-cell transcriptomics, single-cell proteome, single-cell metabolome, and drug development.
Microfluidics is a flexible, precise tool, and it is easy to integrate with different functions. Firstly, it can be used as an important tool to separate rare but important cells according to the cell`s biological or physical properties. Secondly, microfluidics can provide the possibility of single-cell omics. Thirdly, microfluidics can be used in drug development, specifically in drug delivery and drug combination. Meanwhile, droplet microfluidics has gradually become the most powerful tool to encapsulate single-cells with other reagents for DNA, RNA, or protein analysis.
Microfluidics is a robust platform technology that is able to accomplish rare cell separation, efficient single-cell omics analysis and provide a platform for drug development and drug delivery.
Breast cancer continues to pose a significant healthcare challenge worldwide for its inherent molecular heterogeneity. This review offers an in-depth assessment of the molecular profiling undertaken ...to understand this heterogeneity, focusing on multi-omics strategies applied both in traditional bulk and single-cell levels. Genomic investigations have profoundly informed our comprehension of breast cancer, enabling its categorization into six intrinsic molecular subtypes. Beyond genomics, transcriptomics has rendered deeper insights into the gene expression landscape of breast cancer cells. It has also facilitated the formulation of more precise predictive and prognostic models, thereby enriching the field of personalized medicine in breast cancer. The comparison between traditional and single-cell transcriptomics has identified unique gene expression patterns and facilitated the understanding of cell-to-cell variability. Proteomics provides further insights into breast cancer subtypes by illuminating intricate protein expression patterns and their post-translational modifications. The adoption of single-cell proteomics has been instrumental in this regard, revealing the complex dynamics of protein regulation and interaction. Despite these advancements, this review underscores the need for a holistic integration of multiple ‘omics’ strategies to fully decipher breast cancer heterogeneity. Such integration not only ensures a comprehensive understanding of breast cancer’s molecular complexities, but also promotes the development of personalized treatment strategies.
Spatial proteomics elucidates cellular biochemical changes with unprecedented topological level. Imaging mass cytometry (IMC) is a high-dimensional single-cell resolution platform for targeted ...spatial proteomics. However, the precision of subsequent clinical analysis is constrained by imaging noise and resolution. Here, we propose SpiDe-Sr, a super-resolution network embedded with a denoising module for IMC spatial resolution enhancement. SpiDe-Sr effectively resists noise and improves resolution by 4 times. We demonstrate SpiDe-Sr respectively with cells, mouse and human tissues, resulting 18.95%/27.27%/21.16% increase in peak signal-to-noise ratio and 15.95%/31.63%/15.52% increase in cell extraction accuracy. We further apply SpiDe-Sr to study the tumor microenvironment of a 20-patient clinical breast cancer cohort with 269,556 single cells, and discover the invasion of Gram-negative bacteria is positively correlated with carcinogenesis markers and negatively correlated with immunological markers. Additionally, SpiDe-Sr is also compatible with fluorescence microscopy imaging, suggesting SpiDe-Sr an alternative tool for microscopy image super-resolution.
Rapid advances in nanotechnologies are driving the revolution in controlled drug delivery. However, heterogeneous barriers, such as blood circulation and cellular barriers, prevent the drug from ...reaching the cellular target in complex physiologic environments. In this review, we discuss the precise design of nanotechnologies to enhance the efficacy, quality, and durability of drug delivery. For drug delivery in vivo, drugs loaded in nanoplatforms target particular sites in a spatial- and temporal-dependent manner. Advances in stimuli-responsive nanoparticles and carbon-based drug delivery platforms are summarized. For transdermal drug delivery systems, specific strategies including microneedles and hydrogel lead to a sustained release efficacy. Moreover, we highlight the current limitations of clinical translation and an incentive for the future development of nanotechnology-based drug delivery.
PDF
