JPS60251873A - Apparatus for handling fine particle - Google Patents

Abstract

PURPOSE:To operate the movement and stop of fine particles automatically with high accuracy at a high speed, by migrating dielectric fine particles in a buffer solution for a very small distance at a constant voltage, measuring the migration time, and selecting an electrode voltage optimal for handling the fine particles. CONSTITUTION:Fine electrified particles or dielectric fine particles 21 are moved from an electrode 23 to an electrode 24 in a buffer solution 22 by using an electrophoretic force. On the other hand, two electric field effect type transistors 25 having the surface covered with an insulating layer 26 are provided at a given distance, and the gate voltage is changed with the electrified fine particles 21 coming just under the gate of the transistors 25 to change the electric current between the source and drain and detect the presence of the fine particles 21. Thus, the time required for the fine particles 21 to pass through the distance between the gates of the transistors 25 is known to calculate the moving speed o the fine particles 21 between the above-mentioned gate parts. The voltage for migrating the fine particles 21 is adjusted according to the magnitude of the moving speed to operate stably the moving and stop, etc. of the position of the fine particles 21.

Description

[Detailed description of the invention] [Field of application of the invention] The present invention is for positioning microparticles such as cells and blood cells.

The present invention relates to a particle handling device suitable for automating movement stop control.

[Background of the invention]

Conventionally, manipulation of microparticles such as cells was performed using a micropipette under a microscope6.
Operation of various tests such as red blood cells and white blood cells in medical tests,
This is the operation during cell fusion and cell selection in plant cell breeding, and it was necessary to rely on operations using a micropipette when removing or transferring cells one by one.

One idea to solve this situation is to arrange multiple electrodes on a flat surface and use the principles of electrophoresis or dielectrophoresis to perform precise operations such as moving and stopping the position of particles at high speed and automatically. It will be done.

The basic principles of electrophoresis and dielectrophoresis are explained in detail in [Aomizu and Nagai, eds., Electrophoresis Method, Wide Angle Shoten, 1978].

A method of using electrophoresis to perform an automated alternative to conventional micropipette manipulation is illustrated in FIG. In Figure 1, taking advantage of the fact that microparticles 11 such as cells are negatively charged, the potential of electrode 12 is set higher than that of electrode 13, thereby automatically moving a small distance from left to right. . This utilizes the principle of electrophoresis as it is, and by arranging electrodes one-dimensionally or two-dimensionally and controlling the electrode potential, it is possible to move and stop fine particles on a one-dimensional or planar surface.

In these particulate handling methods, particulates are normal!
! It migrates in a liquid called a liquid solution. It is difficult to maintain the physical properties of a buffer solution constant depending on the purpose of handling microparticles. At least the temperature, viscosity, and conductivity of the buffer solution,
It is preferable that fine particles can be handled stably even when the dielectric constant etc. vary.

When the above physical properties change, the electrophoretic force changes, causing movement,
Stopping control becomes unstable, and in severe cases, it becomes impossible to move. Furthermore, if there are variations in the physical properties of the fine particles being handled, a similar situation may occur.

[Purpose of the invention]

An object of the present invention is to provide a particle handling method that can perform precision operations such as moving and stopping the position of particles at high speed and automatically even if the physical properties of the buffer solution or the particles change. .

[Summary of the Invention] The main point of the present invention is to migrate a given microparticle in a given buffer solution over a certain minute distance at a constant voltage, measure the migration time, and use the results to determine the best method for handling the microparticle. The key is to choose a suitable electrode voltage.

[Embodiments of the invention]

An embodiment of the present invention is shown in FIG. 2 below. Figure 2 shows a method in which the particles are charged and electrophoretic force is used to handle the particles.
Assume that the object moves from the electrode 23 to the electrode 24 within the . This corresponds to FIG. Electrode 23 and electrode 24
Two field effect transistors 25 are installed at a certain distance between them. FIG. 3 shows a PNP type transistor, one surface of which is covered with an insulating layer 26.

When a charged particle comes directly under the gate of a field effect transistor, the gate voltage changes, and the presence of the particle can be detected as a change in current between the source and drain. Since two field effect transistors are placed, when a particle moves from the electrode 23 to the electrode 24, it is possible to know the transit time between the gates of the two field effect transistors. A moving speed V is calculated. f! ! If the voltage applied between the pole 23 and the electrode 24 is constant, the electric field in the buffer solution between the two gates takes a constant value X. The dielectric constant of the buffer solution is ε, the viscous resistance is η,
If the surface potential of the fine particles is ignored, E and X are obtained according to the Helmholtz-Smolekofsky formula. By measuring V from this, ζ.

Fluctuations in ε and η can be seen.

That is, the moving speed increases due to an increase in the dielectric constant of the slowly moving liquid and a decrease in viscous resistance, and an increase in the surface potential of the particles accelerates the moving speed. In this way, changes in the electrical properties of the fine particles and buffer solution to be handled can be determined from the size of V, so ■
By adjusting the magnitude of the voltage that causes the particles to migrate according to the value of , stable handling of the particles can be achieved at all times.

An example of how this basic principle is applied is shown in FIG.

It is assumed that cells are classified by the cell characteristic measuring device 31, for example, by measuring shape, size, etc.

Electrodes 33 and 34 are installed at the starting point of Wl platform 32, and cells migrate from left to right. The voltage generator 35 has an electrode 33. ．． A constant voltage is applied to 34. There are two field effect transistors 36,37 between the voltages 33,34,
The passage time of the cells is determined by a measuring device 38. The output 46 of this measuring device is input to a voltage generator 39, and the sorting is done by
0.41 to control the voltages of the electric wires WA41 to WA44, etc. The output of the cell characteristic measuring device 31 is input to the voltage generator 39, and a command 45 is sent to indicate which path to sort depending on the cell information. The voltage generator uses this command and information 46 indicating the properties of the buffer solution to control the drive electrodes 41 to 42.
Generates the optimum voltage for

It should be noted that it is possible to detect fine particles whose surfaces are slightly charged, such as biological cells, by changing the current of a field effect transistor, as reported by the Institute of Electrical Communication Engineers, MBE82-63, PP9.
~14, "Application and Possibility of Cell Level Measurement Using Semiconductor Sensors" by Naohiko Ozaki et al., and it is clear from this that the present invention can be effectively applied to cell handling devices.

〔Effect of the invention〕

According to the present invention, in an apparatus that automatically moves and stops the position of fine particles in a buffer solution using electrophoretic force, Im
It is possible to always move and stop with high precision even if the liquid characteristics or the characteristics of the particles change.

[Brief explanation of the drawing]

FIG. 1 is a cross-sectional view explaining the principle of the particle handling method that is the object of the present invention, FIG. 2 is a cross-sectional view explaining the present invention in detail, and FIG. 3 is a perspective view showing an embodiment of the present invention. be. 11... Fine particle, 12.13... Electrode, 25...
Field effect ml diagram = Φ Figure 2

Claims (1)

[Claims] A particle handling device that moves or stops charged particles or dielectric particles by controlling the potential or electrode area of electrodes arranged on multiple planes. At least two field effect transistors installed along the movement path of the fine particles, and adjusting means for adjusting the potential of the electrode by eliminating the passage time of the fine particles by changing the current of the field effect transistors. Particulate handling equipment.