陣列式生醫整合系統晶片之研究

Integrated Microarray for Bio-manipulation/detection applications

陳至揚(Chih-Yang Chen)

指導教授 ： 金雅琴 ； 林崇榮

國立清華大學/電機資訊學院/電子工程研究所/博士(2011年)

https://doi.org/10.6843/NTHU.2011.00541

摘要

生物晶片的陣列檢測技術是生物技術與醫療檢測技術上的一大突破，利用陣列方式平行處理多種類樣本，不但可以提高檢測效率、大幅縮短檢測時間，此外，陣列技術所需要使用的樣本量較少，反應時間縮短，少量樣本即可用於大量檢測，因此像是愛菲爾陣列晶片 (Affymetrix chip) 與納米基晶片 (Nanogen chip)，不但種類多，應用範圍廣，使用量大，而且已經獲得生檢與醫檢技術上的標準規範認可。生物晶片在生物與檢測技術上是先進的，但是它仍無法擺脫實驗上種種複雜繁瑣的手續與大型儀器的配合，對於需要更快速度與更低檢測成本的需求上，開始有運用半導體技術進入生物晶片領域，以製做一全自動化的實驗室晶片 (Lab on a chip) 為目的。並結合微機電製程技術 (MEMS) 與微流道技術，開發出各種功能的技術產品，包括檢測、取樣、搬移、混合、分離、萃取等等。
低溫多晶矽技術已經發展許久，目前多用於中小型、高速高解析度面版上，低溫多晶矽相較非晶矽面版技術的優點是：高電子電洞遷移率、較低臨界電壓與較佳的電晶體元件特性。然而在元件漏電與製程穩定性上仍有很大幅度的進步空間，本研究提出一個整合型自動化檢測晶片的構想，可以利用標準的低溫多晶矽製程來實現，並且從電路上解決高漏電流造成感測靈敏度低的問題。利用通過電流的微線圈陣列結構產生電磁場的微變化來控制以磁性顆粒為載體的生物樣本進行主動的取樣、搬運等動作；利用感測器陣列提供的影像資料，即時監測取樣與搬運的進行，並可用於感應生物檢測反應中的熒光反應，監測反應的進行；由於製程變異無法克服，本論文的整合型晶片由CMOS製程來完成，並利用辣根性試劑催化熒光發光反應為基礎，成功地將晶片實際應用於生物相關技術使用上。

關鍵字

生醫晶片 ； 感測器 ； 微線圈 ； 整合系統

並列摘要

Biochip technology and array detection are major breakthroughs in biotechnology development. The parallel processing in multiple types of samples in an array can not only improve the detection efficiency and significantly short the detection time, but also reduce the requested sample quantities, which let the less bio-samples are needed and used to do more tests. Therefore, the biochips, such as Affymetrix chip and Nanogen chip series, have a variety of applications in wide ranges, and also have become technical standards in medical examinations and immunoassays. However, the assays using biochips still need cumbersome manual procedures to deal with the samples before applied on the testing onto the biochip. The instruments to read out the information on biochips are always huge, expensive and difficult to move. In order to satisfy the requests in shorter reaction time and lower cost, the new biochip is designed as an automatic laboratory chip with more developed functions by integrating semiconductor fabrication, micro-electric- mechanical system (MEMS), and microfluid system technology.
Low-temperature polycrystalline silicon (LTPS) technology has been developed and used in small-scale panels with high frame-rate and high resolution performances. The LTPS devices get higher electron mobility, lower threshold voltage, and better transistor performances than the devices on the amorphous silicon. But the device leakage and variations in LTPS process are still required to be improved. The thesis proposes a concept of the integration system biochip fabricated by standard LTPS process, and designing a high-sensitivity detector circuit overcoming the leakage issue of LTPS devices in pixels. The biosamples binding on magnetic beads sorted and transported by varying electromagnetic fields, which come from current-controlled microcoil array. Integration chip is built up by CMOS process due to the serious process variations in LTPS. The prototype carries out the concept of integration chip in sorting, sampling, transporting by microcoils and in real-time monitoring by detectors. It is also proved in the application of chemiluminescence in bio-test reactions with HRP labels.

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