整合微光學元件的微流體系統用於細胞分析之開發

本篇論文是研究一個微光學元件整合的微流體晶片，並用於水珠、粒子、與多種細胞的高效能分析。這個微流體晶片是整合具有高折射率的微球透鏡於微流道晶片內，以提升螢光收集效益和平行檢測機制。在水珠檢測方面，透過一個水珠產生器在微流道上游產生水珠，並在下游將流道分枝為64個支流。在粒子和細胞檢測方面，細胞由入口處進入後，分支為32個平行流道，每個流道都有一對側向流，用以將細胞或粒子聚集成一條線排列。平行的32個流道同時檢測細胞實驗中，總效能可達每秒385,400 細胞檢測。而在這篇論文中，使用的微球形透鏡折射率為2.1，因此可以達到很短的焦距。當透鏡直接埋於流道底部，焦點仍然可以座落於流道內部。此方法提供可以使用較密集的流道，因此晶片可以較小，而同樣大小的雷射光點和相機的視野範圍，可以同時分析較多的流道。使用三維的微流道製程，可以提供每個流道都有一組側向流道，且不會增加側向流入口。這個方法解決了微流道在同時載入多流體時，需要解決的載體入口問題。而只要用一個側向流入口來供給64個側向流道、一個樣品入口來提供32個流道樣品流入、和一個出口，來達到同時32個流道檢測。

關鍵字

高效能；高靈敏度；三維微流道；微透鏡陣列；微流流式細胞儀

並列摘要

This thesis reports the microfluidic devices with parallel detection channel embedded microoptics array for versatile high throughput multicolor fluorescence detection. These devices are realized by utilizing solid immersion micro ball lens arrays for high sensitivity and parallel fluorescence detection. For droplet detection, the droplets, produced by a droplet generator in the upstream of device, randomly flow into 64 parallel channels. For cell detection, the cells randomly flow into 32 channel, in which cells got aligned in the center stream. A total throughput of 358,400 cells/s has been accomplished. High refractive index (R.I.) micro ball lenses (R.I.=2.1) are embedded underneath PDMS channels close to cell detection zones in channels. This design permits patterning high N.A. micro ball lenses in a compact fashion for parallel fluorescence detection on a small footprint device. This cell detection device also utilizes 3D microfluidic fabrication to address fluid routing issues in two-dimensional parallel sheath focusing and allows simultaneous pumping of 32 sample channels and 64 sheath flow channels with only two inlets.

並列關鍵字

High throughput ； High sensitivity ； 3D microfluidics ； Microlens array ； Microflow cytometer

參考文獻

[1] J. Pawley, Handbook of biological confocal microscopy: Springer, 2010.

[2] A. L. Givan, Flow cytometry: first principles: John Wiley & Sons, 2004.

[3] H. M. Shapiro, Practical flow cytometry: John Wiley & Sons, 2005.

[4] B. Derjaguin, G. Ja Vlasenko, A. Storozhilova, and N. Kudrjavtseva, "Flow-ultramicroscopic method of determining the number concentration and particle size analysis of aerosols and hydrosols," Progress in Surface Science, vol. 45, pp. 345-367, 1994.

[5] A. Moldavan, "Photo-electric technique for the counting of microscopical cells," Science, vol. 80, pp. 188-189, 1934.

國際替代計量

整合微光學元件的微流體系統用於細胞分析之開發

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