近几年申请工作或是学校，Proposal这种用来展现自己的英文、研究方向、组织与逻辑、资料与情报搜集能力的资料绝对是必备的。
2009年还是有点熟又不太熟的时候....秉持著咱们在细胞与组织工程的研究可是个未知的领域~~~Everything is possible!! 因此有了以下这份PhD研究计划书。

说来汗颜，2013年重新申请学校时，这份2009计划书姐可是只看了几分钟就直接丢进垃圾桶滴。真不知当年那些大师们在看这份计划书的时候是否也是比照办理呢?

这边就别说之前不负责任研究院的那些被评为品质以上的计划书了....现在看到那些我都很想死(掩面)  不过比起其他同事写的... 恩，不予置评。

这边先贴来给自己一个记录吧!!! 诸位若是在某些地方看到类似的研究...说真的他们愿意试试看且能真的作下去，也是奇葩的一种...这边我就不追究了(远目)。

你，也闻到了飘出来的浓浓菜味了吗? (掩面) 这份计划书姐花了约二个星期完成资料搜集，paper阅读、构思与撰写，但当初花了另外两个星期改英文。
超短的东西还需要两周....就知道当年姐的英文多废了。

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Study plan
(for 2009 PhD Application)

 

 The research of liver bioreactor is one of the fields that I can exert my research experience of mechanical engineering, biomedical engineering, opto-electronics, system design, programming, and cell biology. This plan is a dream project about artificial organ that I wish to study in the PhD program; however, my research interest is not only limited to this realm.

 

Background:

The design of liver bioreactor is still a challenge because the key component for its feasibility, pure primary human hepatocytes, cannot be successful cultivated in appropriate quantities for full function [1, 2]. Many methods and hypotheses are provided to find the mechanism to solve this problem. In 2007, Hui [3] provided a micromachine silicon substrate with moving parts to demonstrate that mechanical control of tissue composition and spatial organization can facilitate the future precise investigation of the cell-cell interactions, which could be one of the key methods to solve the mechanism of the proliferation of liver cell. From Wu and Su’s research [5-7], experiments of different types of mechanical reaction, including transient contact of hepatocytes and stem cells provided by Hui [4] may also give the direction to find the relationship between force stimulate and cell proliferation. In this case, micro-fluid channels by BioMEMS devices are capable to fine-tune the flow pattern to apply on the research of this realm. For the further research on molecular and cellular of liver cell, a test of shear stress on cell differentiation and the design of complex flow patterns in bioreactor are also necessary.

 

Objectives:

 

Biomedical system design:

Design a liver bioreactor that can real time monitor and analyze the viability of human hepatocytes, and maintain available quantities of liver cell for full function. The design should consider the interaction of normal and shear stress, compression and 3D controllable turbulence by the dynamic cultivated of the hepatocyte. In addition, the observation should employ types of immunofluorescent method to detect the viability and activation of target cells. A compact motion control system is also necessary to shift the cultivated specimen of nonhuman stem cell to prevent the possible infection from different species. The real time optical monitoring system which is responsible for recording, detecting and analyzing fluorescence which ought to be low damage to all the cells in this bioreactor. Biomechanical Model built by data acquired from this system can also use for the feedback control unit on hepatocyte co-culturing real-time regulation.

 

Applications:

        This system can apply to determine the role of mechanical force and soluble factors in the initiation of hepatocyte proliferation. We can record and analyze cell-cell force interaction by the tunable motion process of this system.

 

Method (The concept of the design):

 

        Each unit of the bioreactor (the left of the picture) contains are show as below. Using a dish-like system (the center of the picture) with micro stepping motor (i.e Piezo electric motor) to control the position of moving parts which can regulate the interval of cell-cell contact (shift action), the gap between different cell (shift action), the exchange of the different cell types (rotate and shift), and the action of isolated regulation. The moving parts might adopt the protocol introduced by Hui [4]. By testing different parameters of gap between cells, we can find the optimal setting of liver cell proliferation. In the isolated system, the movable mechanism should responsible for removing the second specimen to a nearby region of the same dish where with independent in/out medium supply to prevent contamination. By utilizing controllable gates, we can dynamically separate those sections (the right of the picture).

For real time investigation, using LabVIEW to program the motion control system and to record the image data from the optical system integrated in the motion system that can continuously detect fluorescent signal exiting by laser plugged near the unit (does not show in the picture). In this case, mapping different types of fluorescents can find out the influence of complex bioenvironmental control factors and determine the parameters of a perfect environment to available quantities.

Reference：

 

1.         Andersson, H. and A. van den Berg, Microfabrication and microfluidics for tissue engineering: state of the art and future opportunities. Lab Chip, 2004. 4(2): p. 98-103.

2.         Fiegel, H.C., et al., Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory. J Cell Mol Med, 2008. 12(1): p. 56-66.

3.         Hui, E.E. and S.N. Bhatia, Micromechanical control of cell-cell interactions. Proc Natl Acad Sci U S A, 2007. 104(14): p. 5722-6.

4.         Hui, E.E. and S.N. Bhatia, Silicon microchips for manipulating cell-cell interaction. J Vis Exp, 2007(7): p. 268.

5.         Wu, C.C., Li, Y.S., Haga, J.H., Kaunas, R., Chiu, J.J., Su, F.C., Usami, S., and Chien, S., Directional shear flow and Rho activation prevent the endothelial cell apoptosis induced by micropatterned anisotropic geometry. Proc Natl Acad Sci U S A, 2007. 104:p. 1254-1259.

6.         Wu, C.C., Chao, Y.C., Chen, C.N., Chien, S., Chen, Y.C., Chien, C.C., Chiu, J.J., and Yen, B.L., Synergism of biochemical and mechanical stimuli in the differentiation of human placenta-derived multipotent cells into endothelial cells. J Biomech., 2008. 41 813-21.

7.         Su, F.C., Wu, C.C. and Chien, S., Microenvironment and external force in cell and tissue remodeling. J Mech Behav Biomed Mater (In Press, Invited Review)