CN107779399A - 一种用于监测细胞药代动力学的微流控芯片成像系统 - Google Patents
一种用于监测细胞药代动力学的微流控芯片成像系统 Download PDFInfo
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Abstract
本发明涉及一种微流体成像系统，具体是一种高精度灵敏探测器和微流控芯片层，应用于药物筛选和精准医疗领域。其通过在现有微流控芯片基础上集成多功能微阀、正电子探测、图像重建分析等功能模块，并利用计算机进行无人职守自动化控制，开发出一套可以用于现代生物医药开发研究的集样品精密进样、化学反应合成、生物药物筛选、细胞培养和在线药物效果分析于一体的数字化阀控生物医药开发微流平台。实现低成本、高通量的生物医药开发、合成与筛选、病毒抗药性筛选、个体化跟踪给药等功能。
Description
技术领域
本发明涉及一种微流体成像系统，具体是一种高精度灵敏探测器和微流控芯片层，应用于药物筛选和精准医疗领域。
背景技术
目前最为常用的分子影像学技术有核医学成像技术，尤以正电子发射成像PET的分子显像研究最具影响力，当前的正电子发射成像技术仅限于人体或小动物成像且具有设备体积大、成本高、操控难度大等缺点，对体外成像即切除的组织切片的细胞成像尚无应用。本发明结合了微流控芯片和正电子发射成像原理，构造了一个集细胞培养、检测、成像于一体的体外成像系统。
发明内容
本项目通过在现有微流控芯片基础上集成多功能微阀、正电子探测、图像重建分析等功能模块，并利用计算机进行无人职守自动化控制，开发出一套可以用于现代生物医药开发研究的集样品精密进样、化学反应合成、生物药物筛选、细胞培养和在线药物效果分析于一体的数字化阀控生物医药开发微流平台。实现低成本、高通量的生物医药开发、合成与筛选、病毒抗药性筛选、个体化跟踪给药等功能。
具体实施方式
如图1.右图展示了测量细胞对氟代脱氧葡萄糖[18F]FDG的吸收过程：(1)细胞装载到培养格里 (2)将[18F]FDG溶液引入 (3)细胞摄取[18F]FDG (4)将细胞外的[18F]FDG溶液洗净，探测器只测量到细胞内[18F]FDG的浓度，并且通过对从细胞内射出的正电子的探测重建出细胞图像。
说明：[18F]FDG是指氟代脱氧葡萄糖。葡萄糖是人体三大能源物质之一，将可以被PET探测并形成影像的的正电子核素18F标记在葡萄糖上，即形成了[18F]FDG；因为[18F]FDG可准确反映体内器官/组织的葡萄糖代谢水平，因此是目前PET-CT显像的主要显像剂；恶性肿瘤细胞由于代谢旺盛，导致对葡萄糖的需求增加，大多数肿瘤病灶会表现为对[18F]FDG的高摄取，因此可应用[18F]FDG显像可准确判断肿瘤良、恶性以及药物治疗效果，从而正确指导临床治疗决策。
如图2图3，，微流芯片中包含16室细胞培养格。通过电脑控制压力水平和微通道阀门开关，可独立寻址各培养格；9个入口(reagent inlets)和出口(Outlet)端口，用于细胞或生物和化学流体流入流出；颜色代码：蓝色表示流体网络，红色为细胞培养室，黄色为隔离阀。
如图4(a)纤维连接蛋白涂层：纤维连接蛋白溶液(1毫克ML-1)被注入培养格内，以提高环境的生物相容性(b)细胞培养基装载(c)细胞装载：细胞悬浮液通过重力装入培养格内，并且被保持在37℃(d)培养基的循环及细胞喂养
如图5.细胞对[18F]FDG的吸收与成像：(a)在[18F]FDG培养时间为10，30，60和120分钟时，细胞对[18F]FDG摄取的图像(b)成像图像的量化(尚未纠正核素衰变)；每个细胞中的放射性不与[18F]FDG培养时间保持一定的比例关系；快速增长的信号在10分钟和30分钟达到高峰；由于[18F]FDG随着时间的推移而衰变，信号持续下降。
对于图4和5中的实验说明：
在[18F]FDG摄取实验的前一天，U87胶质母细胞瘤细胞(脑癌)被装载到4x3培养格阵列的微流芯片上，以便细胞对微环境的适应，使得细胞很好的贴壁，细胞装载流程见图4；每个培养格约有100个细胞，通过计算机控制，每6小90.时系统更新DMEM培养基供给，微流芯片被存储在一个孵化器内。在实验当天，浓度为1mCi/ml的[18F]FDG溶液被引入芯片上的每个培养格；每一纵列[18F]FDG对细胞培养的时间不同，从左至右分别为10、30、60、120分钟。每个细胞培养格的图像由于细胞个数和[18F]FDG对细胞培养的时间的不同而不同(图5(a))；更具图像得到的信号量化结果显示与图5(b)，其中纵轴是细胞中[18F]FDG的浓度，横轴是[18F]FDG对细胞培养的时间。
Claims (10)
1.这种微流体器件的特征在于，包括：微流体的细胞培养层、电路层和带电粒子检测层。带电粒子检测层设置在靠近所述的微流体的电路层。在操作时，带电粒子检测层探测微流体的电路层中的样品发射出的带电粒子并形成一个二维图像。
2.如1所述的微流体装置，其特征在于，所述带电粒子检测器层包括闪烁晶体材料。
3.如2所述的微流体装置，其特征在于：所述的闪烁体材料是碘化铯晶体。
4.如2所述的微流体装置，其特征在于，所述闪烁材料是一种具有微柱状结构的晶体用以引导光的方向。
5.如2所述的微流体装置，其特征在于，还包括与所述闪烁材料通信的检测系统，所述检测系统用于探测闪烁材料产生的光，闪烁材料产生的光由带电粒子激发产生。
6.如5所述的微流体装置，其特征在于，检测系统包括一个成像传感器和透镜系统，透镜系统被安放在闪烁材料和成像传感器之间用以成像从闪烁体到成像传感器射出的光束。
7.如5所述的微流体装置，其特征在于，所述检测系统包括一光纤板，光纤板设置在所述带电粒子检测层上，成像传感器设置在光纤板上。
8.如1所述的微流体装置，其特征在于，所述带电粒子检测层包括一个半导体检测器。
9.如1所述的微流体装置，其特征在于，所述带电粒子检测层包括一个位置敏感的雪崩光电二极管。
10.如9所述的微流体装置，还包括一个光屏蔽层置于所述带电粒子检测层上方，所述遮光层用以屏蔽从所述位置敏感的雪崩光电二极管发出的光。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109254018A (zh) * | 2018-09-11 | 2019-01-22 | 华中科技大学同济医学院附属协和医院 | 一种放射性药物的药物代谢动力学成像检测系统 |
| CN114438161A (zh) * | 2022-01-30 | 2022-05-06 | 华中科技大学同济医学院附属协和医院 | 监测药物影响生物样本与放射性探针作用的方法及系统 |
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- 2016-08-30 CN CN201610750283.0A patent/CN107779399A/zh active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109254018A (zh) * | 2018-09-11 | 2019-01-22 | 华中科技大学同济医学院附属协和医院 | 一种放射性药物的药物代谢动力学成像检测系统 |
| CN114438161A (zh) * | 2022-01-30 | 2022-05-06 | 华中科技大学同济医学院附属协和医院 | 监测药物影响生物样本与放射性探针作用的方法及系统 |
| CN114438161B (zh) * | 2022-01-30 | 2024-05-03 | 华中科技大学同济医学院附属协和医院 | 监测药物影响生物样本与放射性探针作用的方法及系统 |
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