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Optical sensing in microchip capillary electrophoresis by femtosecond laser written waveguides

机译:飞秒激光写入波导对微芯片毛细管电泳的光学传感

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摘要

Capillary electrophoresis separation in an on-chip integrated microfluidic channel is typically monitored with bulky, bench-top optical excitation/detection instrumentation. Optical waveguides allow confinement and transport of light in the chip directing it to a small volume of the microfluidic channel and collecting the emitted/transmitted radiation. However, the fabrication of optical waveguides or more complex photonic components integrated with the microfluidic channels is not a straightforward process, since it requires a localized increase of the refractive index of the substrate.udRecently, a novel technique has emerged for the direct writing of waveguides and photonic circuits in transparent glass substrates by focused femtosecond laser pulses.udIn this work we demonstrate the integration of femtosecond laser written optical waveguides into a commercial microfluidic chip. We fabricate high quality waveguides intersecting the microchannels at arbitrary positions and use them to optically address with high spatial selectivity their content. In particular, we apply our technique to integrate optical detection in microchip capillary electrophoresis. Waveguides are inscribed at the end of the separation channel in order to optically excite the different plugs reaching that point; fluorescence from the labelled biomolecules crossing the waveguide output is efficiently collected at a 90° angle by a high numerical aperture optical fiber. The sensitivity of the integrated optical detection system was first evaluated filling the chip with a dye solution, obtaining a minimum detectable concentration of 40 pM. udAfter dynamic coating of the microchannels with an EPDMA polymer we demonstrate electrophoresis of an oligonucleotide plug with concentration down to 1 nM and wavelength-selective monitoring of on-chip separation of three fluorescent dyes. Work is in progress on separation and detection of fluorescent-labeled DNA fragments, targeting specific, diagnostically relevant regions of a template DNA, for application to the detection of chromosome aberrations.
机译:芯片上集成微流体通道中的毛细管电泳分离通常使用笨重的台式光学激发/检测仪器进行监测。光波导允许将光限制在芯片中并在芯片中传输,从而将光导引到小体积的微流体通道并收集发射/透射的辐射。但是,光波导或与微流体通道集成在一起的更复杂的光子组件的制造不是简单的过程,因为它需要局部提高基板的折射率。 ud最近,出现了一种新颖的技术,可以直接写入通过聚焦的飞秒激光脉冲在透明玻璃基板中形成波导和光子电路。 ud在这项工作中,我们演示了将飞秒激光写入的光波导集成到商用微流控芯片中的方法。我们制造了在任意位置与微通道相交的高质量波导,并使用它们以高空间选择性光学寻址其内容。特别是,我们将我们的技术应用于将光学检测集成到微芯片毛细管电泳中。在分离通道的末端刻有波导,以光学方式激发到达该点的不同塞子。高数值孔径光纤以90°角有效地收集了穿过波导输出的标记生物分子的荧光。首先评估集成光学检测系统的灵敏度,将染料溶液填充到芯片中,从而获得最低可检测浓度40 pM。在用EPDMA聚合物动态涂覆微通道后,我们展示了低至1 nM浓度的寡核苷酸塞的电泳以及对三种荧光染料在芯片上分离的波长选择性监测。针对模板DNA的特定,诊断相关区域的荧光标记DNA片段的分离和检测工作正在进行中,用于检测染色体畸变。

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