本文選題：細(xì)胞操作　切入點(diǎn)：細(xì)胞移動　出處：《中國科學(xué)技術(shù)大學(xué)》2016年博士論文

【摘要】：單細(xì)胞手術(shù)由于其在生理,病理,和藥理學(xué)研究領(lǐng)域有著重要的作用,已經(jīng)受到越來越多的關(guān)注和研究。然而目前大多數(shù)單細(xì)胞手術(shù)研究僅限于概念演示驗(yàn)證階段。由于沒有有效細(xì)胞手術(shù)系統(tǒng)能夠精確地操作和控制單個細(xì)胞的位置和姿態(tài)角,同時可以處理大批量細(xì)胞以增加操作精度,實(shí)驗(yàn)數(shù)據(jù)的吞吐量和實(shí)驗(yàn)結(jié)果的可靠性,這些都進(jìn)一步阻礙了單細(xì)胞手術(shù)研究進(jìn)步。本文中,建立了一個集成機(jī)器人光鑷的細(xì)胞手術(shù)系統(tǒng)能夠?qū)崿F(xiàn)批量細(xì)胞同時操控,以及單細(xì)胞位置和方位角的精確控制,其中光鑷可以看做是機(jī)器人受控的末端執(zhí)行器進(jìn)行捕獲和操作生物細(xì)胞。本文從以下三個方面進(jìn)行展開。首先,建立了一個自治控制系統(tǒng)實(shí)現(xiàn)細(xì)胞位置的精確控制。該控制策略保證了被捕獲的細(xì)胞能夠始終保持在光鑷中心附近的小鄰域內(nèi),從而確保在整個操作過程中細(xì)胞能夠穩(wěn)定的光捕獲。基于被光鑷束縛的細(xì)胞動力學(xué)方程,提出了一個簡單的飽和PID控制器實(shí)現(xiàn)細(xì)胞位置的漸近調(diào)控。該控制策略不精確依賴于細(xì)胞動力學(xué)模型參數(shù)和細(xì)胞速度的測量。最后實(shí)驗(yàn)驗(yàn)證所提控制策略的有效性。其次,利用機(jī)器人光鑷細(xì)胞操縱系統(tǒng),結(jié)合全息光鑷(HOTs)技術(shù),建立了多組細(xì)胞移動配對框架。所提的細(xì)胞配對方法是基于人工勢場函數(shù)和同心圓思想。設(shè)計(jì)了特定的人工勢能場函數(shù)用于驅(qū)動多組細(xì)胞到達(dá)期望的拓?fù)?同時避障。根據(jù)光鑷俘獲細(xì)胞的動力學(xué)方程,設(shè)計(jì)了基于人工勢能場函數(shù)的控制器來驅(qū)動多組細(xì)胞分別到達(dá)各自的圓。利用同心圓的對稱性,自動實(shí)現(xiàn)多組細(xì)胞配對控制,同時配對的細(xì)胞間距是可控的，配對細(xì)胞的間距依賴于同心圓的拓?fù)浣Y(jié)構(gòu)。用酵母菌細(xì)胞實(shí)驗(yàn)來闡釋本文所提的細(xì)胞配對方法的有效性。最后,本文利用受控的機(jī)器人光鑷平臺,研究了動態(tài)建模和控制多自由度細(xì)胞旋轉(zhuǎn)。采用機(jī)器人控制的全息光鑷產(chǎn)生的兩個光阱來實(shí)現(xiàn)細(xì)胞旋轉(zhuǎn)。首先建立了廣義的細(xì)胞運(yùn)動動力學(xué)模型,該模型涵蓋了細(xì)胞旋轉(zhuǎn)運(yùn)動動力學(xué)方程。利用T-matrix方法來計(jì)算建模光鑷,標(biāo)定了光鑷施加給細(xì)胞的力矩與其在在細(xì)胞內(nèi)坐標(biāo)的關(guān)系。建立的視覺追蹤框架可以提取細(xì)胞旋轉(zhuǎn)過程中的方位角和角速度。根據(jù)簡化的多自由度細(xì)胞旋轉(zhuǎn)的動力學(xué)模型,設(shè)計(jì)了視覺反饋控制器實(shí)現(xiàn)細(xì)胞像平面內(nèi)和像平面外旋轉(zhuǎn)操作。選取具有特征點(diǎn)的酵母細(xì)胞進(jìn)行旋轉(zhuǎn)操控實(shí)驗(yàn)來驗(yàn)證本文所提方法的有效性。概括來說，，基于機(jī)器人光鑷細(xì)胞手術(shù)控制系統(tǒng)能夠提供強(qiáng)有力的平臺實(shí)現(xiàn)細(xì)胞位置和方位角精確控制,以及多細(xì)胞同時操控任務(wù)。自治的細(xì)胞位置控制系統(tǒng)不僅能夠?qū)崿F(xiàn)細(xì)胞操作過程在穩(wěn)定的光鑷捕獲,而且是依賴于細(xì)胞位置的細(xì)胞手術(shù)應(yīng)用或是相關(guān)的生物醫(yī)學(xué)工程領(lǐng)域最基本最重要的操作技術(shù)。多組細(xì)胞配對操作很大程度上提高操作效率和測量結(jié)果的吞吐量。該研究能夠有助于揭示細(xì)胞內(nèi)和細(xì)胞間生理活動的功能機(jī)理。自動的多自由度細(xì)胞旋轉(zhuǎn)控制能夠?qū)崿F(xiàn)細(xì)胞全方位細(xì)胞姿態(tài)控制,它也是許多單細(xì)胞手術(shù)操作過程中最基本卻是非常重要的操作技術(shù)。本文將為探究單細(xì)胞層面的生理和病理機(jī)理研究奠定了堅(jiān)實(shí)的基礎(chǔ)：在精確醫(yī)藥領(lǐng)域,將有助于進(jìn)一步提高細(xì)胞或是亞細(xì)胞層面靶向治療。
[Abstract]:Single cell operation due to the physiology, pathology, pharmacology and plays an important role in research field, is attracting more and more attention and research. However, most studies on single cell operation is limited to the concept demonstration phase. The position and attitude of no effective cell operation system can accurately control the angle of operation and single cells, at the same time can handle a large number of cells to increase the operation precision, reliability and throughput of the experimental results of the experimental data, which further hinders the progress of single cell operation. This paper established an integrated robot cell operation system of optical tweezers can realize mass cell control, and accurate control of position and orientation angle of single cell. The optical tweezers can be seen as the end of the robot controlled actuator is captured and operation of biological cells. This paper from the following three aspects . first of all, set up an autonomous control system to realize the precise control of cell position. The control strategy can guarantee the captured cells can keep a small neighborhood near the center of the optical tweezers, so as to ensure that in the whole process of the cell can stabilize the light trapping. Cell kinetics equation is bound based on optical tweezers. We propose a simple saturated PID controller to realize the position control cell of the control strategy. The asymptotic measurement imprecision dependent on cell kinetics model parameters and cell speed. The experiments verify the effectiveness of the proposed control strategy. Second, using a robot cell control system with optical tweezers, holographic optical tweezers (HOTs) technology. The establishment of multiple groups of cells. The proposed framework of paired mobile cell pairing method is artificial potential field function and concentric circles. Based on the idea of design of the artificial potential field function specific for driving multi group The cells reach the desired topology, and obstacle avoidance. According to the dynamic equation of optical tweezers capture cell, the controller function based on artificial potential field to drive a plurality of cells respectively reach the circular design. By the symmetry of the concentric circle, automatically paired with control group cells, when paired cell spacing is controllable. Distance between paired cells depends on the topological structure of concentric circles. The effectiveness of method of paired with yeast cell experiments to explain the cells. Finally, this paper use optical tweezers controlled robot platform, research the dynamic modeling and control of multi degree of freedom cell rotation. By two optical holographic optical tweezers control robot the implementation of cell rotation. First cell motion dynamics model of generalized is established. The model covers the dynamic cell rotation. The equations of motion to calculate the modeling of optical tweezers using T-matrix method, The calibration of optical tweezers is applied to the relationship between the cell and the coordinate torque within the cell. The establishment of visual tracking framework can azimuth angle and angular velocity rotation in the process of cell extraction. According to the dynamic model of multi DOF rotary cell simplified, visual feedback controller to realize cell image plane and image plane rotation operation the design of rotation control. Experiments to verify the validity of the proposed method are the selection of yeast cells with the feature point. In general, the robot control system of optical tweezers cell surgery can provide powerful platform to realize the precise control of cell position and azimuth based on control and multicellular task. Cell autonomous position control system can not only realize the operation process of cell capture in optical tweezers is stable, and the cell surgery depends on cell location or biomedical engineering. The most basic and the most important technique. Many groups of cells matching operation can greatly improve the operating efficiency and the measurement results of the throughput. Function mechanism of this study will help to reveal the cellular and intercellular physiological activities. Multi degree of freedom rotation control can realize the automatic cell cell cell omnidirectional attitude control, operation technology the most basic is very important and it is many single cell operation process. This paper will lay a solid foundation for the physiological and pathological mechanism research on single cell level: in the precise field of medicine, will help to further improve the cellular or subcellular level in targeted therapy.

【學(xué)位授予單位】：中國科學(xué)技術(shù)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：TP242

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