RU2414255C1 - Method of liquid substance introduction in microcapsules and related device for implementation thereof - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions refers to biotechnology. A method involves microcapsule supply in a liquid flow onto an output of a microchannel plate 2. The diametre of its channels is less than the size of microcapsules which are kept on the input of the microchannel plate 2 after liquid drainage therethrough. A microneedle lattice 3 is moved to pierce a microcapsule enclosure and to introduce a liquid substance. Thereafter, the filled microcapsules are removed by changing the liquid flow direction through the microchannel plate 2 by a reverse one. The device comprises a microchannel plate 2, a channel 1 with a microcapsule containing liquid, a microneedle lattice 3 and a liquid substance container 4. The lattice 3 is coaxial to the microchannel plate 2. The microneedles are connected with the liquid substance container 4. The channel 1 comprises a microchannel plate 2, a microneedle lattice 3, a piston assembly 5 and valves 8, 9 for maintaining single-direction microcapsule containing liquid motion through the microchannel plate 2. The lattice 3 is movable towards the microchannel plate 2 by a distance of microcapsule enclosure piercing.

EFFECT: inventions provide a continuous process of liquid substance introduction simultaneously in a great number of microcapsules.

2 cl, 4 dwg

Description

The invention relates to the field of biotechnology and is intended for the introduction of portions of liquid medicinal compositions and active substances at the same time to a large number of living microorganisms.

Recently, there has been a need for targeted delivery of drugs to human organs affected, for example, by cancer. Delivery can be carried out in various ways, for example, by piercing with a needle, which reaches the affected organ, by moving the ferromagnetic microcapsules through the blood vessels with a magnetic field. Synthetic microcapsules with thin polymer walls or living microorganisms, which are natural microcapsules, can be used as drug carriers. The latter method allows the drug to be targeted through the blood vessels to the desired location in a living organism, such as a person, where capsule microorganisms break up and pass along with metabolic products over time. To implement this method, it is necessary to administer drugs to a very large number of microorganisms. Here, their number should be millions and tens of millions of pieces, which requires the organization of a continuous process of injecting a large number of microorganisms.

The patent literature contains information on methods and devices for introducing microdoses of active substances or genetic material into cells or microorganisms.

A known method and device for introducing active substances into microorganisms from a solution according to RF patent No. 2224556 (publ. February 27, 2004), in which they float freely, through punctures in the wall of microorganisms created by laser radiation. This method is not always acceptable, since it is difficult to control the volume and quality of the substance introduced into the microorganisms.

Known methods and devices in which the active material is introduced into macroscopic volumes of cells by piercing.

In particular, a device for administering drugs through piercing using a microneedle lattice according to the patent of the Russian Federation No. 2209640 (publ. July 15, 1996) connected to the drug reservoir is known. The invention describes specific designs of microneedles, methods of creating an impulse of spraying pressure and adjusting the size of a portion of the drug. The main problems here are the fixation of microorganisms in a strictly defined position and the organization of a continuous injection process.

Closest to the proposed inventions are a method and device for introducing active genetic material (biological substance) into macroscopic conglomerates from cells by the method of puncturing according to US patent No. 5457041 (publ. 10.10.1995).

It uses a microneedle array, at the ends of which the input material is placed and held. The lattice is moved by a coordinate device in the direction of the sample of cellular material fixed in a special holder. A microneedle array moves over the sample and needles enter the cells of the sample. Then the lattice is pulled out of the sample, and the introduced material remains in the cells, breaking away from the tips of the needles during the reverse movement. The penetration depth into the desired layer of cells is regulated by the length of microneedles. The process is monitored under a microscope.

The disadvantage of this method is the need to use macroscopic biological substances for fixing in the holder. The main problem of introducing injections into microorganisms through piercing is their fixation in space at the location of microneedles. Typically, microorganisms float freely in physiological saline or water, and the operation of piercing the wall and injecting is not possible without their clear fixation on a rigid base. Another disadvantage of this invention is the impossibility of organizing a continuous process of administration of the active substance to a large number of microorganisms at once.

The proposed inventions solve the problem of organizing the process of continuous introduction of liquid substances simultaneously into a large number of microcapsules.

This technical result is achieved through the use of the method of introducing liquid substances simultaneously to a large number of microcapsules through the proposed device for its implementation.

To obtain such a technical result in the proposed method for introducing a liquid substance into microcapsules using a microneedle array and a microchannel plate, it is new that microcapsules in the fluid flow are fed into the microchannel plate, while the diameter of its channels is smaller than the size of the microcapsules that are delayed at the entrance to microchannel plate after drainage of fluid through it. Then, the microneedle array is moved until the microcapsule membrane is pierced and a liquid substance is introduced. Then the filled microcapsules are removed, changing the direction of the flow of the fluid flow through the microchannel plate to the opposite.

The distinguishing features of the proposed method are the fixation of microcapsules at the entrance to the channels of the microchannel plate, the diameter of the channels of which is smaller than the size of the microcapsules, by flowing the carrier fluid through the microchannel plate, moving the microneedle array before piercing the shell of the microcapsule and introducing a liquid substance, removing filled microcapsules by changing the direction of the flow stream fluid on the contrary. This allows the introduction of liquid substances simultaneously into a large number of microcapsules by piercing the wall.

To achieve this technical result, a device is proposed for introducing a liquid substance into microcapsules containing a microchannel plate, a microneedle array and a reservoir of a liquid substance introduced into the microcapsule, in which the microneedle array is coaxial with the microchannel plate, and the microneedles communicate with the reservoir of the liquid substance introduced into the microcapsule . The proposed device contains a channel including a microcapsule liquid, in which a microchannel plate, a microneedle lattice, a piston assembly and valves are installed to ensure the movement of liquid with microcapsules through a microchannel plate in the aforementioned channel with liquid in one direction, the microneedle lattice can be moved towards the microchannel plate at a distance piercing the shell of microcapsules. Moreover, the channels in the microchannel plate have a diameter smaller than the size of the microcapsules.

The use of a microchannel plate installed together with a microneedle array in a channel for supplying microcapsules in a fluid stream with a piston assembly and valves providing the necessary direction of fluid flow through the microchannel plate allows one to fix a large number of microcapsules and carry out a continuous process of introducing liquid substances into them.

These features are not identified in other technical solutions when studying the level of this technical field and, therefore, the solution is new and has an inventive step.

The invention is illustrated by drawings, in which: FIG. 1 is a diagram of a device for introducing a liquid substance into microcapsules in the phase of fixing microcapsules on a microchannel plate; figure 2 - diagram of the device in the phase of introduction of the liquid substance into the microcapsules; figure 3 is a view a of figure 2; figure 4 - diagram of the device in the phase of output of microcapsules from the channel.

The proposed device consists of a channel 1 (Fig. 1), in which a microchannel plate 2, a lattice with microneedles 3, and a reservoir of liquid substance 4 introduced into the microcapsules are installed, in which a lattice with microneedles 3 is mounted coaxially with the microchannel plate 2, microneedles communicate with the reservoir of the introduced into the microcapsules of the liquid substance 4, the piston assembly 5 with the piston 6 provide the necessary movement of the liquid with the microcapsules 7 through the microchannel plate 2 in one direction. The entrance to the piston assembly 5 is closed by a microchannel plate 2 through which fluid flows. Depending on the direction of movement of the piston 6, fluid can flow in or out through the channels of the plate 2. Valves 8 and 9 are designed to organize the movement of fluid with microcapsules along channel 1 in one direction - from left to right.

A device that implements in a continuous mode the method of introducing a liquid substance into microcapsules is as follows.

A fluid stream carrying microcapsules 7 is supplied to channel 1. In Fig. 1, the arrows indicate the direction of fluid flow. The valve 8 in this phase of operation passes liquid with microcapsules 7 to the microchannel plate 2 due to the difference in pressure above and below the microchannel plate 2 created by the downward movement of the piston 6. For the same reason, the valve 9 in this phase of operation is closed and does not allow fluid flow flow to the right. In this case, the fluid flow containing the floating microcapsules 7 in it flows through the channels of the microchannel plate 2 downward (see FIG. 1), sucking and fixing the microcapsules 7 at the entrance to the channels, since the channels in the microchannel plate are smaller than the size of the microcapsules 7, diameter. The downward movement of the piston 6 continues until most of the channels in the microchannel plate 2 are filled with microcapsules 7. Monitoring the filling of the microchannel plate 2 with microcapsules 7 can be carried out by the resistance to the movement of the piston 6.

After filling the majority of the channels of the microchannel plate 2 with microcapsules 7, a regular microneedle array 3 is pushed onto the microchannel plate 2. The microneedle array 3 communicates with the reservoir 4 containing the injected liquid substance. The microneedle array 3 is located coaxially with the channels of the microchannel plate 2. After reaching a certain distance between the microchannel plate 2 and the microneedle array 3, at which there is the greatest probability of piercing the walls of the microcapsules 7, the microneedle array 3 stops, the pressure in the reservoir 4 rises for a while and occurs the introduction of a liquid substance in microcapsules 7 (see figure 2, 3). The number of microcapsules 7 into which the liquid substance is introduced will be of the order of the number of channels and microneedles on the microchannel plate 2 and the microneedle array 3. The diameter of the channels on the microchannel plate 2 was selected based on the size of the microcapsules 7 to prevent microcapsules 7 from passing through the channels. After the introduction of a liquid substance, the microneedle lattice 3 moves away from the microchannel plate 2 to its original position. In this case, the valve 8 is open, and the valve 9 is closed, since the piston 6 continues to move downward, maintaining the pressure drop necessary for fixing the microcapsules 7.

Then, the direction of fluid flow through the microchannel plate 2 is reversed by changing the direction of movement of the piston 6, which pushes the fluid through the channels of the microchannel plate 2, as shown in FIG. 4. In this case, the microcapsules 7 are discarded from the microchannel plate 2 and are taken out together with the liquid through the valve 9 to the outlet of the channel 1, and the valve 8 is closed and does not allow the microcapsules 7 to mix before and after the introduction of the liquid substance. Thus, a single cycle of the process of introducing liquid substances into a large number of microcapsules 7 is carried out.

Next, the three-phase cycle of the procedure for introducing a liquid substance is repeated again. In the process of repeating cycles through the drip 1 from left to right, there is a quasi-continuous flow of liquid containing microcapsules 7 before and after the introduction of the liquid substance.

Thus, the use of the proposed inventions allows you to organize a continuous process of introducing liquid substances simultaneously to a large number of microcapsules, thereby increasing the efficiency of the process.

Claims (2)

1. A method of introducing a liquid substance into microcapsules using a microneedle lattice and a microchannel plate, characterized in that the microcapsules in the fluid stream are fed into the microchannel plate, while the diameter of the channels is smaller than the size of the microcapsules that are delayed at the entrance to the microchannel plate after removal through liquids, and then the microneedle array is moved to pierce the shell of the microcapsules and a liquid substance is introduced, after which the filled microcapsules are removed, changing the direction of the fluid flow through microchannel plate reversed. 2. A device for introducing a liquid substance into microcapsules containing a microchannel plate, a microneedle array and a reservoir of a liquid substance introduced into the microcapsule, in which a microneedle array is coaxial with the microchannel plate, and the microneedles communicate with a reservoir of a liquid substance introduced into the microcapsule, characterized in which contains a channel including a microcapsule liquid, in which a microchannel plate, a microneedle array, a piston assembly and valves are installed to provide fluid movement from the microcaps Lamy through microchannel plate in said channel with a liquid in one direction, the array of microneedles is movable toward the microchannel plate to pierce the shell of the microcapsules distance, and channels in the microchannel plate has a smaller diameter than the size of the microcapsules.

Images