KR101643477B1 - Analytical device for the stationary liquid phase lab-on-a-chip - Google Patents

Abstract

The present invention relates to a stationary liquid phase lab-on-a-chip analyzer comprising magnetic particles, comprising: a deck plate for receiving the lab-on-a-chip; At least four columns supporting the deck plate; And a deck vibration motor positioned between the column and the deck plate for applying a vibration to the deck plate, wherein a predetermined portion of the column includes a deck post of a flexible material. And a chip analyzing apparatus.

Description

[0001] The present invention relates to a lab-on-a-chip analyzer,

The present invention relates to a stationary liquid phase wrap-on-a-chip analyzer capable of performing an analysis process using a stationary liquid phase wrap-on-a-chip.

Recently, a technology related to an analyte detecting apparatus capable of easily detecting the analyte by moving the analyte to be analyzed from the sample space to the detection space (Patent No. 10-1398764) has been developed.

More specifically, referring to FIG. 1, the above description relates to a sample space (hereinafter referred to as a sample space) containing a mixed solution of a sample containing an analyte and a reactant containing solid particles 20 11, a sample chamber, a detection chamber 12 containing a detection solution, and a sample chamber 11 and a detection space 12 to prevent the mixed solution from being mixed with the detection solution. The particles 20 in the stationary liquid phase lab-on-a-chip (SLP LOC) 10 including the channel 13 are moved from the sample space 11 to the detection space 12). ≪ / RTI >

The analytical process using the above-described stationary liquid phase wrap-on-a-chip may be performed by placing a reagent containing solid phase particles and a sample in a sample space to cause a binding reaction, And the analyte is analyzed by measuring the signal using the labeling substance bound to the particle. At this time, when the solid particles are magnetic particles, the particles are moved by the magnetic force using the moving means as a magnet.

Particularly, when a reaction product containing a particle and a sample are put in a sample space to perform a binding reaction, a shaking means is required to stir the particles and the reactant. In addition to the binding reaction, such an agitating means may be used for promoting the enzyme reaction when the enzyme is used as a marker particle. Therefore, a means for agitating the analytical process of the analyte using the stationary liquid phase lab-on-a-chip is indispensably required. Therefore, a conventional orbital shaker or a reciprocating shaker has been used as the stirring means. However, when stirring the lab-on-a-chip using a conventional stirrer, there is a problem that the position of the magnet as the moving means and the position of the lab-on-a-chip do not match when stirring is stopped. In order to solve such a problem, if both the moving means and the plate on which the lab-on-a-chip is fixed are installed on the stirrer, a large stirrer is required, and the apparatus becomes large and heavy. In addition, when a solution is contained in a small space such as a sample space or a detection space of a lab-on-a-chip, stirring with a conventional stirrer causes a problem that effective stirring is not performed because the movement of the solution is not large.

In addition, linear actuators have been used as moving means for moving magnetic particles. At this time, a vibration motor can be added to smooth the movement of the magnetic particles. However, when the vibrating motor is attached to one point of the lab-on-a-plate where the lab-on-a-chip is placed, there is a problem that it is difficult to apply the same strength of vibration to several lab-

KR 10-1398764 (registered patent)

The present invention seeks to provide a stationary liquid phase lab-on-a-chip analyzer capable of achieving effective agitation.

The present invention relates to a stationary liquid phase lab-on-a-chip analyzer comprising magnetic particles, comprising: a deck plate for receiving the lab-on-a-chip; At least four columns supporting the deck plate; And a deck vibration motor positioned between the column and the deck plate for applying a vibration to the deck plate, wherein a predetermined portion of the column includes a deck post of a flexible material. Thereby providing a chip analyzing apparatus.

The apparatus for analyzing a stationary liquid phase wrap-on-a-chip according to the present invention includes deck pillars of a flexible material so that vibration can be uniformly applied to the entire deck plate, thereby achieving effective stirring.

1 is a view showing a stationary liquid phase wrap-on-a-chip.
2 is a diagram showing the structure of a stationary liquid phase wrap-on-a-chip analyzer according to the present invention.
3 is a photograph of a stationary liquid phase wrap-on-a-chip analyzer manufactured in an embodiment of the present invention.
Figure 4 is a photograph of a stationary liquid phase wrap-on-a-chip used in an embodiment of the present invention.
5 is a graph showing the stirring efficiency of the stationary liquid phase wrap-on-a-chip analyzer and the track stirrer of the present invention.
FIG. 6 is a graph showing the results of measurement of mixing speed when stirring using the stationary liquid phase wrap-on-a-chip analyzer of the present invention.
FIG. 7 is a graph showing the stirring efficiency of the stationary liquid phase wrap-on-a-chip analyzer and the tracked stirrer of the present invention in a 96-well immunoplate.

The present invention relates to a stationary liquid phase lab-on-a-chip analyzer, comprising: a deck plate for receiving the lab-on-a-chip; at least four columns supporting the deck plate; And a deck vibration motor positioned between the column and the deck plate to apply a vibration to the deck plate, wherein a predetermined portion of the column includes a deck post of a flexible material.

In particular, the deck support may be at least one member selected from the group consisting of springs, sponge, porous plastic, silicone and gel, and the column includes a stirring plate connected to the lower end of the column, . ≪ / RTI >

In addition, the stirring plate may include at least four columns supporting the stirring plate, a predetermined portion of the column may include a flexible stirrer strut, and the stirrer strut may be a spring, a sponge, a porous plastic, Silicone, and gel.

In this case, the deck plate may further include moving means for moving the magnetic particles of the lab-on-a-chip located on the bottom surface of the deck plate. More specifically, the moving means may include driving means provided outside the deck plate, A moving member which is moved in a forward and backward direction by receiving a driving force, a magnet material provided on the moving member and moving along the moving member, and a conical ferromagnetic body provided on the magnet material to move the magnetic particles.

The measuring means may further include measuring means for measuring a signal generated in the lab-on-a-chip, and the measuring means may measure at least one selected from the group consisting of absorbance, a fluorescent material, a luminescent material, Can be measured.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. Prior to this, terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms, and the inventor should appropriately interpret the concepts of the terms appropriately It should be construed in accordance with the meaning and concept consistent with the technical idea of the present invention based on the principle that it can be defined.

Therefore, the embodiments described in this specification and the configurations shown in the drawings are merely the most preferred embodiments of the present invention and do not represent all the technical ideas of the present invention. Therefore, It is to be understood that equivalents and modifications are possible.

FIG. 2 is a diagram showing the structure of a stationary liquid phase wrap-on-a-chip analyzer according to the present invention. FIG. 3 is a schematic diagram of a stationary liquid phase wrap- FIG. 5 is a graph showing the stirring efficiency of the stationary liquid phase wrap-on-a-chip analyzer of the present invention and the track stirrer, FIG. 6 is a graph showing the stirring efficiency of the stationary liquid phase wrap- FIG. 7 is a graph showing the results of measurement of mixing speed when stirring with a stationary liquid phase wrap-on-a-chip analyzer of the present invention. FIG. 7 is a graph showing the stirring efficiency Fig. Hereinafter, a stationary liquid phase wrap-on-a-chip analyzer according to the present invention will be described in detail with reference to FIGS. 1 to 7 and embodiments.

The present invention relates to a stationary liquid phase wrap-on-a-chip analyzer capable of performing an analysis process using a stationary liquid phase wrap-on-a-chip.

2, the present invention relates to a stationary liquid phase lab-on-a-chip analyzer 1 comprising magnetic particles comprising a deck plate 100 for receiving a lab-on-a-chip 10, And a deck vibration motor (120) positioned between the column (110) and the deck plate (100) to apply vibration to the deck plate (100) On-a-chip analyzer (1) comprising a deck post (111) of a flexible material.

More specifically, the deck plate 100 can accommodate one or a plurality of lab-on-a-chip 10, and when the plurality of lab-on-a-chip 10 is accommodated, vibration is uniformly distributed throughout the deck plate 100 A plurality of deck vibration motors 120 may be used. Particularly, by attaching the deck vibration motor 120 to four corners of the deck plate 100, vibration can be uniformly applied to the entire deck plate 100. Further, since the deck vibration motor 120 is not used for inducing the movement of the solution in the lab-on-a-chip 10 but is used for vibrating the particles, it is preferable to use a vibration motor capable of applying a small amplitude and high vibration . As an example, a coin motor can be used.

In addition, there are at least four pillars 110 that support the deck plate 100 of the present invention, and certain portions of the pillars 110 include deck pillars 111 of flexible material.

Here, the flexible material means a material that can be flexibly deformed and absorbs impacts, examples of which include springs, sponges, porous plastics, silicones, and gels. When the deck support (111) is made of a flexible material, the shape and strength of the vibration can be controlled by controlling the structure, material and flexibility of the support. For example, a low-strength spring or sponge can be used to vibrate freely in all directions.

On the other hand, the stationary liquid phase lab-on-a-chip analyzer 1 includes a stirring plate 200 connected to a lower end of the column 110, and the stirring plate 200 includes a stirring vibration motor 220 .

Particularly, the stirring vibration motor 220 may be a simple structure fixed to the stirring plate 200, and the stirring plate 200 may include at least four columns 210 like the deck plate 100 And a predetermined portion of the column 210 may include a stirrer support 211 of a flexible material.

Here, the stirrer struts 211 may be at least one selected from the group consisting of springs, sponges, porous plastic, silicon and gel.

The four pillars 210 supporting the stirring plate 200 may be installed on the stirrer base 230. The static liquid-phase wrap-on-a-chip analyzer 1 of the present invention can move the entire stirring plate 200 using the vibration when the stirring vibration motor 220 installed on the stirring plate 200 rotates, It is possible to stir the deck plate 100 installed above.

Particularly, the stirring vibration motor 220 according to the present invention is characterized by the number of revolutions of the stirring vibration motor, the degree of the center of gravity deviation from the axis of the stirring vibration motor 220, the structure and material of the deck support 111 and the stirrer support 211 Various types of agitation can be performed.

For example, when a spring or a sponge is used as a material for the deck support 111 and the stirrer support 211, the deck support 111 and the stirrer support (211) is used, it is possible to perform shaking stirring mainly in the lateral direction rather than in the vertical direction.

Since the analyzer according to the present invention can control the movement of the solution in a much more various manner than the conventional stirrer, optimum mixing conditions can be found according to the size and shape of the space or the tube containing the solution. For example, when the solution is contained in a relatively large space such that the solution can be shaken, the silicon tube is used as the deck support 111 and the stirrer support 211, and the stirring vibration motor 220 is rotated So that the solution can be shaken in the horizontal direction. On the other hand, when the space containing the solution is small, it may be more effective to make the liquid oscillate by applying vibration rather than shaking. In addition, by operating the dehydrating vibration motor 120 while operating the stirring vibration motor 220, it is possible to induce two types of motion in the solution. Therefore, it is possible to efficiently mix the solution in the microtube or the solution contained in the microplate.

For example, the stirring vibration motor 220 may be a cylinder vibration motor.

In addition, the stationary liquid phase lab-on-a-chip analyzer 1 of the present invention may further include a moving means 300 for moving magnetic particles. More specifically, the moving means 300 may be located on the bottom surface of the deck plate 100.

Particularly, the moving means 300 includes a driving means 310 installed outside the deck plate 100, a moving member 320 receiving the driving force of the driving means 310 and translating in the forward and backward direction, And a conical ferromagnetic body 331 disposed on the magnet member 330 and moving the magnetic particles 330. The conical ferromagnetic body 331 is disposed on the movable member 320 and moves along the moving member 320.

Here, the ferromagnetic body 331 refers to a material which is strongly magnetized in the direction of the magnetic field when a strong magnetic field is applied from the outside, and remains magnetized even when the external magnetic field disappears, and the magnetic particles move through the channel 13 And is formed in a conical shape. This is to concentrate the magnetic force of the magnet at one point because it is advantageous to collect the magnetic particles at a small point in the narrow channel 13. [ The magnet material 330 may be a permanent magnet or an electromagnet, and the driving unit 310 may use a linear actuator capable of translating the moving member 320.

Further, the stationary liquid phase wrap-on-a-chip analyzer 1 according to the present invention may further include measuring means capable of measuring a signal generated in the lab-on-a-chip. More specifically, the label may be at least one selected from the group consisting of coloring, luminescence, fluorescence, catalytic activity, magnetic activity and radioactivity. Optical methods for measuring optical signals such as absorption, fluorescence, luminescence, and surface plasmon resonance, or electrochemical methods for measuring electrical signals by chemical reaction can be mainly used. In order to automatically perform the entire analysis process on the stationary liquid phase wrap-on-a-chip 10, such measurement means may be included in the analysis apparatus.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example >

Example  One. Stationary liquid phase Lab-on-a-chip  Production of analytical equipment

In this embodiment, the stationary liquid phase wrap-on-a-chip analyzer 1 of the present invention was manufactured.

Referring to FIG. 3, the stirrer base 230 was manufactured by adhering an acrylic column 210 having a length of 1 cm and a length of 1 cm to four corners of an acrylic plate having a length of 10 cm and a length of 12 cm, and a thickness of 5 mm. The linear actuator was manufactured by itself, and the stirrer base 230 was installed on the case.

The stirrer was manufactured by fixing a stirring vibration motor to the lower surface of the acrylic structure having the same structure as the stirrer base 230. Here, the silicon tube was used as the stirrer support 211, and the four corners of the stirring plate 200 were connected to the four pillars 210 of the stirrer base 230. Since the stirrer support 211 at this time is made of a flexible material, the stirrer plate 200 moves independently of the stirrer base 230 when the stirrer vibration motor 220 vibrates and the deck plate 100).

The deck plate 100 was made of acrylic having a length of 10 cm and a length of 12 cm and a thickness of 2 mm. A coin motor was attached to the underside of the four corners of the deck plate 100 to serve as a deck vibration motor 120. It is also possible to connect the deck vibration motor 120 and the column 110 in the stirring plate 200 by using a flexible deck support 111 made of a sponge so that the deck plate 100 is separated from the stirring plate 200 So that it can vibrate.

In addition, the magnet material 330 for particle movement uses a neodymium magnet having a length and a diameter of 1 cm, respectively, and a conical iron, which is a ferromagnetic material 331 having a diameter of 1 cm and a height of 1 cm, Respectively. The magnet is connected to the moving part of the linear actuator through the moving member 320. The linear actuator means the driving means 310 of the present invention.

In the present embodiment, measurement means for measuring a signal is not provided.

Example  2. Stationary liquid phase Lab-on-a-chip  Analytical Stirring  Efficiency evaluation

In this embodiment, the efficiency of stirring with a trajectory shaker was evaluated using the lab-on-a-chip analyzer 1 according to the present invention.

In this embodiment, the lab-on-a-chip 10 shown in Fig. 4 is used. The lab-on-a-chip 10 includes three sample spaces 11, a detection space 12 and a buffer space 14, and the sample space 11, the detection space 12 ) And the buffer space (14) to prevent the mixing solution and the detection solution from being mixed with each other. At this time, the sample space 11 of the lab-on-a-chip 10 had a pentagonal shape, and the total size was 8 × 10 mm at the base and 5 mm at the height.

10 g of protein particles (G-MP, Thermo) functionalized with protein G, 100 ng of lkine phosphatase-linked anti-goat immunoglobulin G antibody (AP-Ab) and B buffer (0.25% BSA in PBS , Triton X-100) was placed and placed on a conventional trajectory stirrer and the stationary liquid phase wrap-on-a-chip analyzer (1) of the present invention, followed by stirring for 30 minutes. For comparison, the same reactants were placed in 15 ml microtube and reacted for 30 minutes in a vortex vortex. After each reaction, the contents were washed with phosphate buffered saline (PBS) and alkaline phosphatase (AP) enzyme activity bound to G-MB was measured.

As a result, as shown in FIG. 5, when the sample was stirred by the analyzing apparatus of the present invention, it was slightly lower than that of the microtube, but higher than that of the conventional trajectory stirrer. Therefore, it can be seen that the analyzer according to the present invention is simpler and smaller than the conventional stirrer, but the stirring efficiency is higher than that of the conventional stirrer. Here, it is judged that the value of the track stirrer or the analyzing apparatus of the present invention is lower than the comparative value because of the loss of the particles.

Next, 10 g of G-MP, 10 ng of AP-Ab and 0.2 ml of B buffer were added to the sample space of the lab-on-a-chip 10 in the analyzer of the present invention and placed in the analyzer according to the present invention. The chip 10 was taken out, and 10 μl of the supernatant was collected by collecting G-MP with a magnet to measure the AP enzyme activity. As a result, as shown in FIG. 6, the equilibrium was reached within 10 minutes, and it was confirmed that the binding reaction occurred very rapidly.

Finally, the agitation efficiency was evaluated in a 96-well immunoplate. Protein G was adsorbed to the immunoplate wells, blocked with buffer B, and 10 ng of AP enzyme was added thereto. The enzyme activity was measured in a supernatant by placing the sample in a conventional shaker and an analyzer according to the present invention with stirring . As a result, as shown in FIG. 7, the activity of the enzyme increased more rapidly than that of the conventional stirrer, indicating that the stirring efficiency was excellent.

1: lab-on-a-chip analyzer
10: lab-on-a-chip 11: sample space
12: detection space 13: channel
14: buffer space 20: particles
100: Deck plate 110: Column
111: Deck holding 120: Deck vibration motor
200: stirring plate 210: pillar
211: stirrer support 220: stirring vibration motor
230: stirrer base
300: moving means 310: driving means
320: moving member 330: magnet material
331: ferromagnet

Claims (9)

1. A stationary liquid phase lab-on-a-chip analyzer comprising magnetic particles,
A deck plate for receiving the lab-on-a-chip;
At least four upper pillars supporting the deck plate, the pillars including a deck support of a partially flexible material;
A deck vibration motor positioned between the upper column and the deck plate for applying vibration to the deck plate;
A stirring plate connected to a lower end of the upper column, the stirring plate including a stirring vibration motor; And
At least four lower pillars supporting the stirring plate and including a stirrer support of a predetermined part flexible material; On-a-chip analyzing device.
The method according to claim 1,
Wherein the deck support is at least one selected from the group consisting of springs, sponges, porous plastic, silicon and gel.
delete delete The method according to claim 1,
Wherein the stirrer strut is at least one selected from the group consisting of a spring, a sponge, a porous plastic, silicon, and gel.
The method according to claim 1,
And a moving means for moving the magnetic particles of the lab-on-a-chip located on the bottom surface of the deck plate.
The method according to claim 6,
The moving means
Driving means provided outside the deck plate;
A moving member that receives the driving force of the driving unit and translates in the forward and backward direction;
A magnet material installed on the moving member and moving along the moving member; And
And a conical ferromagnetic body provided on the magnet material for moving the magnetic particles.
The method according to claim 1,
Further comprising measurement means capable of measuring a signal generated in the lab-on-a-chip.
9. The method of claim 8,
The measuring means
Wherein at least one selected from the group consisting of fluorescence, absorbance, fluorescence, luminescent material, electric signal and magnetic field is measured.

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