以表面電位控制之次微米細胞塗布技術之研發

Abstract

隨著醫療技術與微機電系統的日益成熟，細胞晶片的發展越來越受到矚目與重視。如何能利用此成熟的技術，將微機電系統的優點移轉至細胞晶片或細胞感測器上，已成近年來熱門的研究主題。而若要成功發展細胞晶片，如何能夠對蛋白質及細胞進行有效且準確的塗布，佔有相當關鍵的地位。目前已成功發展的塗布技術，如利用壓模轉印圖樣的微壓印技術[1](microcontact printing)、利用微奈米製程的微影技術[2](photolithography)與藉介電泳動效應實現細胞塗布的介電泳動技術[3](dielectrophoresis)等，雖有其各自的優點，但以上幾種方法，皆無法同時達成高解析度、高效率與對細胞無潛在損害的目標。 基於此，本研究中應用電致濕潤現象(eletrowetting)。此現象能依所加電壓而改變表面的親疏水性質，而親疏水間作用力是生物分子間重要的非共價作用力之一。因此經由外加電壓調控，能夠控制表面的性質，即改變表面與生物分子的附著力，並且進而達到生物分子與細胞的精準塗布。於本研究中，證實了此方法的可行性，細胞塗布圖樣可由電極圖樣決定，並且其細胞塗布解析度可達到次微米等級。更重要的，此技術能夠避免不必要的熱能及電解現象產生，亦不會有電場或機械應力而對欲塗布的細胞造成不良影響。由以上結果可證實，本技術未來可望對生物晶片與細胞晶片的塗布技術提供一個新的方向與動力。

As the medical technology and micro-electromechanical systems become mature, the development of cell chips are also more and more important. It has become a hot research topic for decades to try to achieve useful and efficient cell chips by taking advantage of micro-electromechanical technology. Needless to say, to the successful development of cell chips, it is crucial how we effectively and accurately pattern biomolecules and cells. The developed patterning technologies, such as microcontact printing, photolithography, and dielectrophoretic patterning, however, cannot achieve goals of high efficiency, high patterning resolution and no damage to biomolecules. In order to solve this problem, here we have applied the technique of electrowetting, which can change the surface hydrophobicity/hydrophilicity by applying voltage. The hydrophobicity/hydrophilicity is one of the most important non-covalent forces for biomolecules. Thus, through the regulation of applied voltage, surface properties can be controlled, and therefore the attachment of biomolecules and cells can further be precisely manipulated. In this research, we prove that cell patterns can be confined in the regions of electrode patterns, and patterning resolution can be down to sub-micrometer scale. Besides, this technique can avoid unnecessary generation of electrolysis and heat, and the possible negative influence of the electric field or mechanical stress can also be excluded. Based on previous results, it is certain that this technique can provide a new direction for biomolecular and cell patterning techniques and also benefit the development of biochips and cell chips.