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具有超高时间分辨率的微流控芯片内流体的光谱分辨流动成像。

Spectrally resolved flow imaging of fluids inside a microfluidic chip with ultrahigh time resolution.

作者信息

Harel Elad, Pines Alex

机构信息

Materials Sciences Division, Lawrence Berkeley National Laboratory, and Department of Chemistry, University of California, Berkeley, CA 94720, USA.

出版信息

J Magn Reson. 2008 Aug;193(2):199-206. doi: 10.1016/j.jmr.2008.04.037. Epub 2008 May 9.

Abstract

Microfluidics has advanced to become a complete lab-on-a-chip platform with applications across many disciplines of scientific research. While optical techniques are primarily used as modes of detection, magnetic resonance (MR) is emerging as a potentially powerful and complementary tool because of its non-invasive operation and analytical fidelity. Two prevailing limitations currently inhibit MR techniques on microfluidic devices: poor sensitivity and the relatively slow time scale of dynamics that can be probed. It is commonly assumed that the time scale of observation of one variable limits the certainty with which one can measure the complementary variable. For example, short observation times imply poor spectral resolution. In this article, we demonstrate a new methodology that overcomes this fundamental limit, allowing in principle for arbitrarily high temporal resolution with a sensitivity across the entire microfluidic device several orders of magnitude greater than is possible by direct MR measurement. The enhancement is evidenced by recording chemically resolved fluid mixing through a complex 3D microfluidic device at 500 frames per second, the highest recorded in a magnetic resonance imaging experiment. The key to this development is combining remote detection with a time 'slicing' of its spatially encoded counterpart. Remote detection circumvents the problem of insensitive direct MR detection on a microfluidic device where the direct sensitivity is less than 10(-5) relative to traditional NMR, while the time slicing eliminates the constraints of the limited observation time by converting the time variable into a spatial variable through the use of magnetic field gradients. This method has implications for observing fast processes, such as fluid mixing, rapid binding, and certain classes of chemical reactions with sub millisecond time resolution and as a new modality for on-chip chromatography.

摘要

微流控技术已经发展成为一个完整的芯片实验室平台,应用于许多科研领域。虽然光学技术主要用作检测方式,但磁共振(MR)因其非侵入性操作和分析保真度,正成为一种潜在的强大且互补的工具。目前有两个主要限制阻碍了微流控设备上的MR技术:灵敏度差以及可探测的动力学时间尺度相对较慢。通常认为,对一个变量的观测时间尺度限制了测量互补变量的确定性。例如,短观测时间意味着光谱分辨率差。在本文中,我们展示了一种新方法,该方法克服了这一基本限制,原则上允许实现任意高的时间分辨率,且在整个微流控设备上的灵敏度比直接MR测量高出几个数量级。通过以每秒500帧的速度记录通过复杂三维微流控设备的化学分辨流体混合情况,证明了这种增强效果,这是磁共振成像实验中记录到的最高速度。这一进展的关键在于将远程检测与其空间编码对应物的时间“切片”相结合。远程检测规避了微流控设备上直接MR检测不灵敏的问题,在该设备上,直接灵敏度相对于传统核磁共振小于10^(-5),而时间切片通过利用磁场梯度将时间变量转换为空间变量,消除了有限观测时间的限制。这种方法对于观察快速过程具有重要意义,例如流体混合、快速结合以及某些具有亚毫秒时间分辨率的化学反应类别,并且作为芯片色谱的一种新模式。

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