可即時檢測心肌細胞行為之壓電換能器開發

Abstract

在目前心血管的研究以及心血管藥物篩檢中，心肌細胞的特徵行為是重要檢測的參數之一，其中包括施力曲線、收縮表現、跳動頻率等特性，因此，檢測心肌細胞收縮行為的平台也相繼的被提出，而其中又以微機電製程為主軸，發展柔性結構的設計與微流體系統的設計應用最為廣泛。 但目前研究中，檢測心肌細胞收縮行為的平台，最為常見的都是以光學儀器觀測細胞本身或透過基材形變，並擷取高精度的影像訊號，進行後端處理進而得到細胞的形變曲線，間接的推射細胞的施力行為。為了能達到自動化且直接性的量測心肌細胞的施力曲線，本研究提出一種檢測平台的設計，以聚偏二氟亞乙烯(polyvinylidene fluoride; PVDF)的柔性壓電聚合材料做為壓電換能器的核心，為了保持其壓電特性，本研究開發出製程溫度低於55oC的低溫製造技術，製作出壓電換能器陣列。並結合智能結構進行開發三項仿生技術，包含細胞對於壓電基材的從屬性、促使細胞對壓電基材產生依附性、微組織培養技術，並成功的誘導心肌微組織產生自發性的跳動。最終，本研究架設可自動化量測心肌微組織自我收縮之介面系統，成功的量測到心肌細胞的週期性收縮訊號，實現可自動化且直接性檢測心肌細胞施力訊號的目標。

Current challenges for cardiovascular research and cardiovascular drug screening is the necessity to study the biomechanical responses of cardiomyocytes, such as, force profile, systolic and diastolic forces, beating frequency, contraction rate. Hence, the detecting platforms for monitoring contracting behaviors of cardiomyocytes have been proposed, while the design of flexible substrate and MEMS based microfluidic system were most widely use. However, the majority of reported methods were based on high quality images to calculate the deformation and strain of cardiomyocytes. Then the actual mechanical force and stress were estimated by measured strain values. It is an indirect detection and could not infer the actual force output of a cardiomyocyte. In this study, a detection platform for real time monitoring contracting behaviors of cardiomyocytes was developed. A flexible polyvinylidene fluoride (PVDF) thin-film was chosen to serve as the core of the piezoelectric transducer. In order to preserve its piezoelectric property, low temperature fabrication process that could control overall processing temperature to be lower than 55oC was developed. Piezoelectric transducer arrays were successfully microfabrication. Tissue engineering technique was introduced to develop a biomimetic substrate for promoting cardiomyocyte maturation. Finally, an interface system that can monitor the force response of cardiac microtissues was implemented. Experimental results demonstrated that the mechanical information of the cardiac mictotissues could automatically be converted into electrical signals by the piezoelectric transducer.