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Spatially resolved and multiplexed MicroRNA quantification from tissue using nanoliter well arrays

机译:使用纳米孔井阵列从组织中分辨和多路复用的微小罗纳量化

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Spatially resolved gene expression patterns are emerging as a key component of medical studies, including companion diagnostics, but technologies for quantification and multiplexing are limited. We present a method to perform spatially resolved and multiplexed microRNA (miRNA) measurements from formalin-fixed, paraffin-embedded (FFPE) tissue. Using nanoliter well arrays to pixelate the tissue section and photopatterned hydrogels to quantify miRNA, we identified differentially expressed miRNAs in tumors from a genetically engineered mouse model for non-small cell lung cancer (K-rasLSL-G12D/+; p53fl/fl). This technology could be used to quantify heterogeneities in tissue samples and lead to informed, biomarker-based diagnostics. MicroRNA is a short, noncoding RNA molecule that regulates many biological processes and is emerging as a biomarker; a method has been developed to perform spatially resolved, measurements of multiple microRNA directly from formalin-fixed, paraffin-embedded (FFPE) tissue. Spatially resolved gene expression patterns are becoming a key area in medical studies, including diagnostics, but technologies for quantification and multiplexing in this area have been limited. Using a mouse model, a team headed by Patrick S. Doyle at the Massachusetts Institute of Technology, USA has succeeded in developing a method based on nanoliter well arrays for microRNA quantification. The team demonstrated that its technology allows greater multiplexing and better special resolution than can be achieved with existing methods. The authors consider that their technology has excellent potential for quantifying heterogeneities in FFPE tissue for next-generation biomarkers.
机译:空间分辨的基因表达模式作为医学研究的关键组成部分,包括伴随诊断,但量化和多路复用技术有限。我们介绍了一种从福尔马林固定的石蜡包埋(FFPE)组织中进行空间分辨和多路复用的微小RONE(miRNA)测量的方法。使用纳米孔阱阵列以将组织截面和PhotoPatterned水凝胶分析到量化miRNA,我们在来自非小细胞肺癌的遗传工程小鼠模型中鉴定了差异表达的miRNA(K-RaslSL-G12D / +; P53FL / FL)。该技术可用于量化组织样本中的异质性,并导致基于生物标志物的诊断。 MicroRNA是一种短的非沉积RNA分子,可调节许多生物过程,并作为生物标志物而涌现;已经开发了一种方法来直接从福尔马林固定的石蜡嵌入(FFPE)组织直接进行空间分辨,测量多个microRNA。空间分辨的基因表达模式正在成为医学研究的关键区域,包括诊断,但该区域中的量化和多路复用技术受到限制。使用鼠标模型,由Patrick S. Doyle在马萨诸塞州理工学院领导的团队成功地开发了基于纳米孔井阵列的方法进行MicroRNA量化。该团队证明其技术允许更大的多路复用和比现有方法所实现的更好的特殊分辨率。作者认为,它们的技术具有对下一代生物标志物的FFPE组织中的异质性具有优异的潜力。

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