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Mass spectrometry imaging of glycans from tissue sections and improved analyte detection methods

机译:来自组织切片的聚糖的质谱成像和改进的分析物检测方法

摘要

The presently disclosed subject matter provides methods using mass spectrometry for direct profiling of N-linked glycans from a biological sample. In addition, the embodiments of the present invention also disclose novel methods, known as targeted analyte detection (TAD), for improving the detection limit of MALDI-MS. These methods take advantage of the carrier effect of the added standard analytes, which occurs due to the generic sigmoidal shape of the calibration curve. The functionality of TAD depends on the relative enhancement of sensitivity over the increase of the standard deviation at the analysis of target analytes with spiking in exogenous concentration. At certain ranges of exogenous concentration, the increment in the sensitivity overcomes the standard deviation, resulting in an improved LOD. Theoretically, exogenous concentrations approximately at 1 LODorig would generate the optimum LOD improvement. TAD is a cost-effective LOD improvement method, which is not limited to a certain group of analytes, or detection methods or instruments. It can be applied to enhance the detection of any analyte with different detection methods, provided that the analyte of interest can be extracted or is available in synthetic form.
机译:本公开的主题提供了使用质谱法从生物样品中直接分析N-连接的聚糖的方法。此外,本发明的实施例还公开了新颖的方法,称为靶向分析物检测(TAD),用于提高MALDI-MS的检测限。这些方法利用了添加的标准分析物的载流子效应,这是由于校准曲线的通用S形而产生的。 TAD的功能取决于在分析目标分析物时,外源浓度加标,灵敏度相对于标准偏差的增加相对提高。在一定范围的外源浓度下,灵敏度的增加克服了标准偏差,从而提高了LOD。从理论上讲,大约1 LODorig的外源浓度会产生最佳的LOD改善。 TAD是一种具有成本效益的LOD改进方法,不限于特定种类的分析物,检测方法或仪器。如果可以提取感兴趣的分析物或以合成形式提供,则可以将其应用于通过不同的检测方法来增强对任何分析物的检测。

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