RU2267092C2 - Method and device for batching and delivering microscopic mass of liquid - Google Patents

Abstract

FIELD: apparatus for measuring by volume and delivering fluids.

SUBSTANCE: method comprises irradiating three-phase interface between the liquid, gas, and solid substrate by light beam, and generating microscopic liquid drop whose volume depends on the duration of irradiation, light intensity, and the distance from the center of the light beam and three-phase interface. When the volume of the drop reaches a given value, it is caused to move over the solid substrate to a given site by moving the light spot over the surface of the solid body. The measurements are carried out by visual observation. The light source should be absorbed by liquid or solid body. The device comprises substrate provided with microscopic cavities and microscopic passages that connect the cavities. The substrate is covered with the optically transparent window so that light can reach microscopic cavities and passages. The window is provided with microscopic openings for supplying and discharging liquid from the microscopic cavities and receiving pickups.

EFFECT: enhanced reliability.

2 cl, 13 dwg

Description

The present invention relates to the field of microfluidics, combinatorial and analytical chemistry, biotechnology and pharmaceuticals and can be used for non-contact dosing and movement of liquid droplets from microreserves containing as solutions of liquids with various biological or other objects such as DNA molecules, viruses, microbes included in their volume microdroplets of liquid, solid particles, etc., and without them, through a network of microchannels to other microreserves for chemical reactions or analysis.

Known microfluidic actuator [1], which allows to dose the volume of liquid and pump it through microchannels. The principle of operation of this actuator is to create a differential pressure along the microchannels connecting the tanks, due to the electrically controlled depressurization of the vacuum chamber connected to one of the tanks.

This actuator does not allow multiple pumping and makes high demands on the tightness of the vacuum chamber.

A known method and device [2], allowing to form and move segments of small volumes of liquid, where each segment is separated by a segmenting liquid. The liquid segments may contain various reagents, molecules and particles that are delivered to the analytical sensors in this microfluidic device. The fluid is driven by electrokinetic forces (electroosmosis) induced by the potential difference applied to the electrodes that are placed along the microchannel and are in contact with the fluid.

The disadvantages of this method and device include the need for direct contact of the electrodes with a liquid. In addition, the disadvantages of electrokinetic pumping methods are their sensitivity to contaminants that are adsorbed on the walls of microchannels; the release of Joule heat in a liquid; high control voltage reaching several hundred volts;

the appearance of products of an electrochemical reaction — gas bubbles clogging microchannels [3].

The article [4] describes a method for thermocapillary pumping of discrete drops of liquid in microchannels. In this method, when one of the ends of a droplet located in a microchannel is heated, by means of resistive heaters mounted in the wall of the microchannel, a difference in surface tension is created between the opposite ends of the droplet, which causes the difference in capillary pressure, which causes the droplet to move.

The disadvantages of this method are the high operating temperature difference (up to 70 ° C) between the ends of the droplet, which does not allow it to be used for pumping liquids with a low boiling point or liquids containing biological objects. The use of Peltier cooling elements to increase the temperature difference without increasing the average drop temperature significantly complicates the design of the device and the pumping procedure.

The patent [5] discloses a method for forming microdroplets of a liquid and a method for pumping them through microchannels. Drops are formed by injecting portions of gas through a hydrophobic hole in the wall of the microchannel, partially filled with liquid. Further, droplets separated from the main fluid are pumped through the microchannel under the action of thermocapillary forces caused by heating of one of the droplet ends using a microheater lattice mounted in the microchannel wall.

Significant disadvantages of the presented method of forming droplets is the use of additional micropumps, as well as the need for special treatment of the inner surface of the microchannel to make it hydrophobic. The disadvantages of thermocapillary transport of microdrops are described above.

Thus, devices for implementing the proposed methods are extremely difficult to manufacture, and the methods themselves are difficult to control due to the use of a large number of control elements.

The proposed method and device can significantly simplify the process of dispensing microvolumes (microdrops) of liquid and make it controlled; move microdroplets without contact, which is important in the case of aggressive liquids; to simplify the manufacture of the device, as there is no need to apply insulating and hydrophobic layers, as well as form lattices of resistive heaters, or electrodes.

The method consists in using the concentration-capillary (CC) effect induced by the thermal action of optical radiation for dosing and moving liquid droplets of liquid [6, 7]. This effect is observed in solutions containing a volatile component, which decreases the surface tension (PN) of the solution with increasing concentration. If a beam of light that is absorbed by a liquid or the surface of a solid is directed to a three-phase liquid / gas / solid interface of such a solution, then local evaporation of the volatile component occurs due to local heating of the solution. Since the concentration of the indicated component decreases in the irradiated region, the surface tension of the solution increases here. On the free surface of the liquid, a surface tension difference (i.e., a pulling force) arises directed toward the heating region. Under the action of a pulling force, the fluid flows into this region and forms a microdrop (Fig. 1a), which grows in size (Fig. 1b). Upon reaching microdroplets of certain sizes, it independently moves away from the three-phase boundary (Fig.1c). Then in the same place the next microdrop is formed (Fig. 1d), i.e. the process is repeated. The size of the microdroplet, isolated from the main volume of the solution, depends on the time of irradiation, the beam intensity and the distance from the center of the beam to the three-phase boundary, as well as on the composition of the solution. Selecting the specified parameters of the beam, microdroplets of a given volume can be dosed.

Figure 1 shows the sequential stages of the formation of a separate microdrop: 1a - the emergence of microdrops in the irradiation region, 1b - the growth of microdrops, 1c - self-removal of the microdrops from the main volume of the solution, 1g - the appearance of the following microdrops. The liquid was a 5% solution of iodine in acetone, where acetone was the volatile component. Irradiation was carried out by a focused beam of a DRSh-100 mercury lamp with a power of about 30 mW. The interval between shots is 2 s.

After the microdroplet is formed, it can be moved on a solid surface in a non-contact manner, using the same CC effect induced by the thermal effect of light. For this, the beam that caused the formation of the microdrop is displaced in the direction where the microdrop is to be moved. The temperature is higher on the side of the microdrop near the beam boundary, which causes a more intense evaporation of the volatile component and an increase in surface tension. On the surface of the microdroplet, flows arise that transfer the substance of the microdroplet from its part remote from the center of the beam, where the PN is smaller, to the part closest to the beam. These currents cause the movement of microdrops behind a beam of light.

Figure 2 shows the motion picture of a microdroplet from a 5% solution of iodine in ethanol into the light beam (the interval between frames is 6 s, the beam power is 20 mW, the droplet diameter is about 300 μm), and Figure 3 shows drops from a 5% iodine solution in bromine (the interval between frames is 4 s, the beam power is 30 mW, the diameter of the droplet in the first frame is about 400 μm).

An example diagram of a device for dispensing and moving trace amounts of liquid with eight micro reservoirs is shown in FIG. 4 (general view), FIG. 5 (top view), FIG. 6 (front view), FIG. 7 (side view), FIG. 8 ( view in cross section A-A '), Fig. 9 (view in cross-section B-B'), and the principle of its operation is explained in Figs. 10-13 (view in cross-section A-A ').

Here: 1 - a substrate (e.g. carbolite, ebonite, quartz or silicate glass), 2 - a window that is transparent to optical radiation (e.g. quartz or silicate glass), 3-10 - microholes for input / output of liquids into microreserves, and also for entering into the micro-tanks of analytical sensors, 11-18 - micro-tanks, 19-25 - micro-channels, 26 - liquid. Microreservoirs 11, 12, 14, 15, 17, and 18 are conveniently used as storages for the studied liquids and liquid reagents, and microreservoirs 13 and 16 are used as microreactors or as microreserves for analyzing liquids.

The device operates as follows. The microvolumes of the studied liquids containing various inclusions or without them are pumped using a microsyringe into the microreservoirs through the microholes in window 2. Then the microvolumes of these liquids are dosed and transferred with the help of a light beam from one microreservoirs to others for chemical reactions or analysis.

Consider the process of dispensing and moving fluid from a micro reservoir 11 to a micro reservoir 13. To generate a micro droplet, optical radiation of any source is used (for example, a laser, an LED, an arc discharge lamp, an incandescent lamp), for which window 2 is transparent and the liquid is absorbing. The radiation of this source is directed to a three-phase boundary in the micro reservoir 11, Figure 10. The thermal effect of radiation causes a CC effect, which leads to the formation of a microdroplet of liquid in the region of incidence of the beam, Fig.11. Upon reaching the microdroplets of the required volume, which is controlled by observing it through the window 2, it is moved from the micro reservoir 11 along the microchannel 19 to the micro reservoir 13 by shifting the same light beam along the indicated path, Figs. 12 and 13.

In a similar manner, the dropping and movement of liquid droplets from any other microreservoir are carried out.

Devices with any other number of microreservoirs, randomly interconnected by microchannels, are possible and easily implemented.

Thus, the presented method and device have the following advantages.

The processes of dispensing and moving microvolumes of liquids are greatly simplified, since they are carried out using the same beam of light, and additional devices such as micropumps or vacuum chambers are not required.

Dosing and moving are carried out non-contact, which is important when working with aggressive, toxic and radioactive liquids.

A wide selection of optical radiation sources is available (lasers, LEDs, arc gas discharge lamps and incandescent lamps), it is enough that the source radiation is absorbed by the substance of the dosed and transported liquid, or the substrate material of the device.

The process of dispensing microdrops can be controlled by observing it through a transparent window, which makes it easy to obtain microdrops of a given volume.

The manufacture of the device is also significantly simplified, because there is no need to apply insulating and hydrophobic layers, and form lattices of resistive heaters, or electrodes. It is enough to make a window transparent for optical radiation.

In this case, for the manufacture of the device, you can use a material with any thermal and electrical characteristics (e.g. silicon, quartz, silicate glass, ceramics, plastics). Only the chemical inertness of this material with respect to dosed liquids is necessary, and for the window material, in addition, transparency to optical radiation.

Since the implementation of the method does not require noticeable heating of the liquid (when using highly volatile components of the solution, such as acetone or chloroform with a boiling point of 56.2 and 61.1 ° C [8], heating by 10-20 ° C from room temperature is sufficient) and it does not flow electric current, then both true solutions and solutions including transported objects, such as biological, chemical and other materials, such as DNA molecules, bacteria, blood cells, proteins, can act as substances of dosed and transported liquids, Biofilms cells, spores, peptides, proteins, colloidal and solid particles, pigments, microdroplets of liquid immiscible with the liquid carrier, etc. It is sufficient that a volatile component is included in the solution, which decreases the surface tension with increasing concentration. Such components are easy to select, for example, in the case of aqueous solutions, they can be low molecular weight alcohols or ketones.

LITERATURE

1. US patent N6521188, 2003, 18 Feb. J.R. Webster. Microfluidic Actuator.

2. US Patent 6,524,456 Bl. J. M. Ramsey, S. C. Jacobson. Microfluidic Devices for the Controlled Manipulation of Small Volumes. Feb.25, 2003.

3. G. M. W. Whiteides, A. D. Stroock. Flexible Methods for Microfluidics. // Physics Today, Vol. 54, N.6, pp. 42-48, 2001.

4. T. S. Sammarco, M. A. Burns. Thermocapillary Pumping of Discrete Drops in Microfabricated Analysis Devices. // AlChE Journal, Vol. 45, No.2, pp. 350-362,1999.

5. US patent N6130098. C. Handique, B. Gogoi, M. Bums, C. Mastrangelo. Moving Microdroplets. 10 Oct. 2000.

6. Bezugly B.A. Capillary convection controlled by the thermal action of light, and its application in methods of recording information. Diss ... Ph.D. -mat. Sciences, Moscow, Moscow State University, 1983.

7. Bezuglyi B.A. Photoinduced solutocapillary convection: New capillary phenomenon. Rev. Proc. 1 st Int. Symp Hydromech Heat / Mass Transfer Microgr. Perm-Moscow, Russia, July 6-14, 1991. Gordon & Breach Sci. Publ. - 1992. - P.335-340.

8. Physical quantities: Reference. Ed. Acad. Grigoryeva I.S., Mikhailova E.Z. - M .: Energoatomizdat, 1991.

Claims (2)

1. A method of dispensing and moving microfluids of a liquid, characterized in that a concentration-capillary effect caused by the thermal action of light is used for dosing and transporting microfluids of a liquid, dosing of the liquid is carried out by irradiating a three-phase liquid / air / solid substrate with a light beam, the amount of dosed liquid is determined the irradiation time, the beam intensity and the distance from the center of the beam to the three-phase boundary, moving the dosed volume of liquid the movement of the light spot of the same beam on the surface of the solid substrate, the monitoring of the dosing processes and the movement of trace amounts of liquid is carried out visually, while the spectral composition of the light beam such that the liquid and / or material of the solid substrate on which it is located absorbs this radiation, and in the composition of the liquid includes a volatile component, which decreases the surface tension with increasing concentration. 2. A device for dispensing and moving micro amounts of liquid in the form of a substrate, in the volume of which there are microreserves and microchannels connecting them, closed by a window transparent to optical radiation so that there is optical access to microreserves and microchannels, and in the window above the microreserves there are microholes.

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