公开(公告)号：EP2322271A1

公开(公告)日：2011-05-18

申请号：EP10188635.6

申请日：2010-10-25

Applicant: FEI COMPANY ,  Stichting Het Nederlands Kanker Instituut

Inventor： Van Veen, Gerard ,  Dona, Pleun ,  De Jong, Frank ,  Peters, Jacobus

IPC: B01J19/00 ,  B01L3/00 ,  H01J37/20

CPC classification number: B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00824 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/0086 ,  B01J2219/00905 ,  B01J2219/0097 ,  B01L3/502761 ,  B01L7/54 ,  B01L2200/0668 ,  B01L2300/0822 ,  B01L2400/0415 ,  B01L2400/0439 ,  B01L2400/0442 ,  B01L2400/0487 ,  G01N2021/058 ,  H01J37/20 ,  H01J37/26 ,  H01J2237/2004 ,  Y10T436/143333

Abstract: The invention relates to a micro-reactor (100) for observing small particles, cells, bacteria, viruses or protein molecules in a fluid. The micro-reactor shows a first channel (106) formed between two layers (102, 104) for containing the fluid, with an inlet (112) and an outlet (114), the two layers separated by a first distance. A likewise second channel (108) with an inlet (118) and an outlet (116) is placed adjacent to the first channel. A gap connects the first channel and the second channel, at the gap at least one layer showing a window (120) transparent to the method of inspection and at the window the two layers being separated by a very small distance of, for example, 1 µm or less.
The micro-reactor may be used with an optical microscope (in which all particles are in focus), inspection with a Scanning Transmission Electron Microscope (in which the range of the electrons is limited), inspection with soft X-rays in the 250-500 eV range (also showing a limited range), etc.
A method of using the micro-reactor includes applying a gradient over the gap, thereby causing the particles to cross the gap. The gradient may be static or dynamic, and may be a gradient in concentration, of a chemical or biological material, in pressure, in temperature, in electric potential, or in magnetic field. By detecting a property of the particles upstream in the first channel, e.g. using fluorescent labels on the particles, and then applying a pressure burst over the channels when the property meets certain preset criteria, only selected particles can be placed in the gap.

Abstract translation: 本发明涉及用于观察流体中的小颗粒，细胞，细菌，病毒或蛋白质分子的微反应器（100）。 微反应器示出在两个层（102,104）之间形成的用于容纳流体的第一通道（106），其具有入口（112）和出口（114），这两层分开第一距离。 同样具有入口（118）和出口（116）的第二通道（108）与第一通道相邻放置。 间隙连接第一通道和第二通道，在间隙中至少一层显示对检查方法透明的窗口（120），并且在窗口处两层间隔非常小的距离，例如1 μm或更小。 微反应器可以与光学显微镜一起使用（其中所有颗粒都聚焦），使用扫描透射电子显微镜（其中电子范围受限）检查，使用软X射线在250- 500eV范围（也显示有限的范围）等。使用微反应器的方法包括在间隙上施加梯度，由此导致颗粒穿过间隙。 梯度可以是静态的或动态的，并且可以是浓度，化学或生物材料，压力，温度，电势或磁场中的梯度。 通过检测第一通道中上游颗粒的特性，例如， 在颗粒上使用荧光标记，然后当性质符合某些预设标准时在通道上施加压力脉冲，只有选定的颗粒可以放置在间隙中。

公开(公告)号：EP2316565A1

公开(公告)日：2011-05-04

申请号：EP09174002.7

申请日：2009-10-26

Applicant: FEI COMPANY

Inventor： Dona, Pleun ,  Van Veen, Gerard ,  Peters, Jacobus ,  De Jong, Alan

IPC: B01J19/00 ,  B01L3/00 ,  H01J37/20

CPC classification number: B01J19/0093 ,  B01J2219/00783 ,  B01J2219/00824 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/0086 ,  B01J2219/00905 ,  B01J2219/0097 ,  B01L3/502761 ,  B01L7/54 ,  B01L2200/0668 ,  B01L2300/0822 ,  B01L2400/0415 ,  B01L2400/0439 ,  B01L2400/0442 ,  B01L2400/0487 ,  G01N2021/058 ,  H01J37/20 ,  H01J37/26 ,  H01J2237/2004 ,  Y10T436/143333

Abstract: The invention relates to a micro-reactor (100) for observing small particles, cells, bacteria, viruses or protein molecules in a fluid. The micro-reactor shows a first channel (106) formed between two layers (102, 104) for containing the fluid, with an inlet (112) and an outlet (114), the two layers separated by a first distance. A likewise second channel (108) with an inlet (118) and an outlet (116) is placed adjacent to the first channel. A gap connects the first channel and the second channel, at the gap at least one layer showing a window (120) transparent to the method of inspection and at the window the two layers being separated by a very small distance of, for example, 1 µm or less.
The micro-reactor may be used with an optical microscope (in which all particles are in focus), inspection with a Scanning Transmission Electron Microscope (in which the range of the electrons is limited), inspection with soft X-rays in the 250-500 eV range (also showing a limited range), etc.
A method of using the micro-reactor includes applying a gradient over the gap, thereby causing the particles to cross the gap. The gradient may be static or dynamic, and may be a gradient in concentration, of a chemical or biological material, in pressure, in temperature, in electric potential, or in magnetic field. By detecting a property of the particles upstream in the first channel, e.g. using fluorescent labels on the particles, and then applying a pressure burst over the channels when the property meets certain preset criteria, only selected particles can be placed in the gap.

Abstract translation: 本发明涉及用于在流体中观察小颗粒，细胞，细菌，病毒或蛋白质分子的微反应器（100）。 微反应器示出了形成在用于容纳流体的两个层（102,104）之间的第一通道（106），其具有入口（112）和出口（114），两个层分开第一距离。 具有入口（118）和出口（116）的同样的第二通道（108）被放置成与第一通道相邻。 间隙连接第一通道和第二通道，在间隙处，至少一层显示对于检查方法是透明的窗口（120），并且在窗口处，两层被隔开非常小的距离，例如1 μm以下。 微反应器可以与光学显微镜一起使用（其中所有颗粒都在焦点中），用扫描透射电子显微镜（其中电子的范围被限制）进行检查，在250- 500eV范围（也显示有限范围）等。使用微反应器的方法包括在间隙上施加梯度，从而使颗粒穿过间隙。 梯度可以是静态或动态的，并且可以是化学或生物材料在压力，温度，电位或磁场中的浓度梯度。 通过检测第一通道上游的颗粒的性质，例如， 在颗粒上使用荧光标记，然后当性能达到某些预设标准时，在通道上施加压力突发，只有选定的颗粒才能放置在间隙中。