Chip type capillary electrophoresis apparatus

Abstract

The utility model belongs to the field of electrophoresis, and particularly relates to a chip type capillary electrophoresis apparatus which comprises a chip and an optical detection module, the sample unit comprises a sample pore plate and a first driving module, and the first driving module is used for three-dimensionally moving the sample pore plate; the electrophoresis unit comprises a first bracket, a bearing seat and a second driving module, the chip is arranged on the bearing seat, the second driving module is used for two-dimensionally moving the bearing seat, and the bearing seat is arranged on the upper side of the sample pore plate; the third driving module is used for driving the optical detection module; the sample unit, the electrophoresis unit, the optical detection module and the third driving module are arranged in a shell, and an opening allowing the sample pore plate and the bearing seat to pass through is formed in the front side of the shell. The device has the advantages of simple structure and the like, and can be applied to electrophoretic analysis.

Description

Technical Field

[0001] The utility model relates to electrophoresis analysis, in particular to a chip-type capillary electrophoresis instrument. Background Art

[0002] Capillary electrophoresis instrument is an essential instrument for biopharmaceutical companies.

[0003] The research on capillary electrophoresis technology abroad is relatively mature, and its products are mainly concentrated in instrument companies such as SCIEX, Agilent, and PerkinElmer, such as:

[0004] SCIEX products only analyze a single sample at a time, with low throughput and long processing time, making them unsuitable for early drug discovery.

[0005] Agilent and Perkin Elmer have launched capillary electrophoresis products based on microfluidic chips. These products utilize a quartz substrate and utilize wet etching to create microscopic channels on the chip surface, allowing analytes to flow and separate within these channels. This chip-based electrophoresis significantly reduces analysis time while maintaining separation efficiency. Due to its superior performance, these instruments are increasingly being used in early-stage drug discovery and hold significant market potential. However, the high cost of the instruments and reagents has limited their widespread adoption.

[0006] NEC has launched a portable chip electrophoresis test device, primarily for use in criminal investigations. By integrating electrophoresis with other nucleic acid reactions, this chip can perform on-site DNA fingerprinting within 25 minutes, significantly reducing detection time. Chip electrophoresis is also often coupled with mass spectrometry.

[0007] Thermo Fisher has launched the ZipChip product, which connects chip electrophoresis to a mass spectrometer via an ESI source, primarily for proteomics analysis. This technology addresses the limitations of traditional liquid chromatography-mass spectrometry for charge differential analysis.

[0008] Domestic capillary electrophoresis research is primarily concentrated in institutions such as the capillary electrophoresis team at the Dalian Institute of Physical Chemistry, Chinese Academy of Sciences, the capillary electrophoresis team at Shanghai Jiao Tong University, Shanghai Tongwei Analytical Technology Co., Ltd., and Beijing Huayang Limin Instrument Co., Ltd. Universities and research institutes primarily focus on prototype technology research, with little consideration given to the long-term reliability of the instruments and user experience. Currently, domestic manufacturers' products are only suitable for single-sample analysis and late-stage drug quality control. There are no domestically produced products on the market suitable for high-throughput screening in early drug development. In early drug development, the number of samples can far exceed the capabilities of modern analytical laboratories. As the number of samples increases, high-throughput analytical platforms with superior precision, automation, and ease of use are required. Summary of the Invention

[0009] In order to solve the deficiencies in the above-mentioned prior art solutions, the utility model provides a chip-type capillary electrophoresis instrument.

[0010] The purpose of this utility model is achieved through the following technical solutions:

[0011] A chip-type capillary electrophoresis instrument comprises a chip and an optical detection module; the chip-type capillary electrophoresis instrument further comprises:

[0012] A sample unit, comprising a sample well plate and a first driving module, wherein the first driving module is used to move the sample well plate in three dimensions;

[0013] An electrophoresis unit, comprising a first bracket, a supporting seat, and a second driving module, wherein the chip is disposed on the supporting seat, and the second driving module is used to move the supporting seat in two dimensions, wherein the supporting seat is disposed on the upper side of the sample well plate;

[0014] a third driving module, configured to drive the optical detection module;

[0015] The sample unit, the electrophoresis unit, the optical detection module and the third driving module are arranged in the housing, and the front side of the housing has an opening allowing the sample well plate and the supporting seat to pass through.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] 1. Achieved high-throughput detection;

[0018] Utilizing a matrix-type sample well plate, multiple samples (e.g., 96 compartments) can be loaded onto the machine at once for automatic sample extraction, automatic internal standard mixing, sequential sample loading, electrophoresis separation, laser detection, and spectrum analysis.

[0019] 2. Compact structure;

[0020] Sample extraction, internal standard mixing, sample loading, electrophoresis separation and detection are all integrated in the shell, with a small size and compact structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The disclosure of the present invention will become more easily understood with reference to the accompanying drawings. Those skilled in the art will readily understand that these drawings are merely used to illustrate the technical solution of the present invention and are not intended to limit the scope of protection of the present invention.

[0022] Figure 1 It is a schematic structural diagram of a chip-type capillary electrophoresis instrument of the present invention;

[0023] Figure 2It is a structural schematic diagram of a sample unit of the present utility model;

[0024] Figure 3 It is a structural schematic diagram of a sample unit of the present utility model;

[0025] Figure 4 It is a structural schematic diagram of the electrophoresis unit of the present utility model;

[0026] Figure 5 It is a partial structural diagram of the electrophoresis unit of the present utility model;

[0027] Figure 6 It is a structural diagram of the detection unit of the utility model;

[0028] Figure 7 It is a structural diagram of the optical detection module of the present utility model.

[0029] In the accompanying drawings, 1-shell, 11-front door, 12-opening, 2-sample unit, 21-first drive module, 22-sample well plate, 23-sample holder, 24-standard centrifuge tube, 25-buffer centrifuge tube, 3-electrophoresis unit, 31-first bracket, 32-valve group adapter block, 33-valve group, 34-vertical guide rail, 35-chip, 36-carrying seat, 37-second bracket, 38-first guide rail, 39-RFID detection board, 4-detection unit, 41-optical detection module, 42-third drive module, 411-light source, 412-collimating lens, 413-dichroic mirror, 414-reflecting mirror, 415-first converging lens, 416-first filter, 421-second converging lens, 422-first detector, 423-second filter, 431-beam splitter, 432-imaging lens, 433-second detector. DETAILED DESCRIPTION

[0030] Figure 1-Figure 7 The following description describes optional specific embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. In order to teach the technical solution of the present invention, some conventional aspects have been simplified or omitted. Those skilled in the art should understand that variations or replacements derived from these specific embodiments will be within the scope of the present invention. Those skilled in the art should understand that the following features can be combined in various ways to form multiple variations of the present invention. Therefore, the present invention is not limited to the following optional specific embodiments, but is only limited by the claims and their equivalents.

[0031] Example 1

[0032] A chip-type capillary electrophoresis instrument according to an embodiment of the present invention is as follows: Figure 1 Shown, including:

[0033] The shell 1, the sample unit 2, the electrophoresis unit 3 and the detection unit 4 are arranged in the shell 1, and the front side of the shell 1 has an opening 12 that allows the sample well plate 22 and the supporting seat 36 to pass through, and the front door 11 is used to control the opening and closing of the opening 12.

[0034] like Figure 2 As shown, the sample unit 2 includes a sample well plate 22 and a first driving module 21 . The first driving module 21 is used to move the sample well plate 22 in three dimensions. The three-dimensional movement includes forward and backward movement, up and down movement, and left and right movement.

[0035] like Figure 4 As shown, the electrophoresis unit 3 includes a first bracket 31, a supporting seat 36 and a second driving module. The chip 35 is arranged on the supporting seat 36. The second driving module is used to move the supporting seat 36 in two dimensions. The supporting seat 36 is arranged on the upper side of the sample well plate 22. The two-dimensional movement includes forward and backward movement and up and down movement.

[0036] like Figure 6 As shown, in the detection unit 4 , the third driving module 42 is used to drive the optical detection module 41 .

[0037] In order to reduce the complexity of the structure, further, as Figure 3 As shown, the sample holder 23 is arranged on the first driving module 21 , and the buffer centrifuge tube 23 and the standard centrifuge tube 24 are arranged on the sample holder 23 and are located on the side of the sample well plate 22 .

[0038] like Figure 4 As shown, the valve group 33 and the valve group adapter block 43 are arranged on the upper side of the first bracket 31.

[0039] like Figure 5 As shown, the second driving module includes a vertical guide rail 34, a first guide rail 38 and a motor. The first guide rail 38 is arranged on the second bracket 37 and extends along the front and rear directions. The supporting seat 36 is arranged on the first guide rail 38. The second bracket 37 is arranged on the vertical guide rail 34 and moves up and down under the drive of the motor; the vertical guide rail 34 is arranged on the first bracket 31.

[0040] In order to improve the detection accuracy, further, as Figure 7As shown, the optical detection module 41 includes an excitation light path and a fluorescence detection light path. In the excitation light path, the excitation light emitted by the light source 411 passes through the collimating lens 412, and is then reflected by the dichroic mirror 413 and the reflector 414 in sequence. The reflected light passes through the first converging lens 415 and is focused on the channel of the chip 35. In the fluorescence detection light path, the fluorescence excited in the channel passes through the first converging lens 415, and is then reflected by the reflector 414. The reflected light passes through the dichroic mirror 413 and the second converging lens 421 in sequence and is received by the first detector 422.

[0041] In order to realize the auto-focus function, further, as Figure 7 As shown, the optical detection module also includes a focusing optical path, in which the fluorescence passing through the dichroic mirror 413 is reflected by the beam splitter 431, and the reflected light passes through the imaging lens 432 and is received by the second detector 433. The fluorescence passes through the dichroic mirror 413, the beam splitter 431, and the second converging lens 421 in sequence.

[0042] Example 2

[0043] According to the application example of the chip-type capillary electrophoresis instrument in Example 1 of the present invention.

[0044] In this application example, if Figure 1 As shown, the sample unit 2, the electrophoresis unit 3 and the detection unit 4 are arranged from bottom to top in the housing 1. The front side of the housing 1 has an opening 12 that allows the sample well plate 22 (in the sample unit 2) and the supporting seat 36 (in the electrophoresis unit 3) to enter and exit. The front door 11 is arranged at an angle on the front side for controlling the opening and closing of the opening 12.

[0045] like Figure 2 As shown, the first drive module 21 includes drive modules for front-to-back, left-to-right, and up-and-down movement. Each drive module includes a guide rail, a motor, and a timing belt (or rack), thereby achieving three-dimensional movement of the sample holder 23. The structure and operation of the first drive module 21 are conventional in the art.

[0046] like Figure 3 As shown, the sample well plate 22 is arranged on the sample holder 23 , and the standard centrifuge tube 24 and the buffer centrifuge tube 25 are arranged on the sample holder 23 and are located on the side of the sample well plate.

[0047] like Figure 4 As shown, in the electrophoresis unit 3 , the vertical guide rail 34 is arranged on the rear side of the first bracket 31 , the valve group 33 and the valve group adapter block 32 are arranged on the upper side of the first bracket 31 , and the support seat 36 of the chip 35 is arranged on the lower side of the valve group adapter block 32 .

[0048] like Figure 5As shown, a second bracket 37 is mounted on a vertical guide rail 34, a first guide rail 38 extending in the front-to-back direction is mounted on the second bracket 37, and a support base 36 is mounted on the first guide rail 38. This allows the chip to move forward and backward while also being driven by a motor to move up and down along the vertical guide rail 34, achieving two-dimensional movement. An RFID detection plate 39 is mounted on one side of the support base 36. When the support base 36 moves rearward along the first guide rail 38 and stops, it engages with a connector on the second bracket 37, thereby detecting that the support base 36 has reached the set position.

[0049] like Figure 6 As shown, in the detection unit 4, the optical detection module 41 is arranged on the third driving module 42, and the third driving module 42 provides three-dimensional movement. The specific structure and working method can be found in the previous patent CN117871647A.

[0050] like Figure 7 As shown, in the optical detection module 41, in the excitation light path, the excitation light emitted by the light source 411 passes through the collimating lens 412 and the first filter 416, and is then reflected by the dichroic mirror 413 and the reflector 414 in sequence. The reflected light passes through the first converging lens 415 and is focused on the microchannel of the chip 35 to excite fluorescence.

[0051] In the fluorescence detection optical path, the excited fluorescence passes through the first converging lens 415 and is then reflected by the reflector 414. The reflected light passes through the dichroic mirror 413, the beam splitter 431, the second filter 423 and the second converging lens 421 (imaging lens) in sequence and is received by the first detector 422.

[0052] In the focusing optical path, the fluorescence passing through the dichroic mirror 413 is reflected by the beam splitter 431 , and the reflected light passes through the imaging lens 432 and is received by the second detector 433 .

[0053] The working mode of the chip-type capillary electrophoresis instrument in the embodiment of the utility model is:

[0054] Add the sample to be tested into the sample well plate 22 and place it on the sample holder 23, and also put in the standard centrifuge tube 24 and the buffer centrifuge tube 25;

[0055] Place the chip 35 containing the reagents on the carrier 36; operate the instrument key input loading to complete the loading of samples and consumables.

[0056] The sample unit 2 drives the sample holder 23, which in turn moves the chip 35 holder 36 inward until it aligns with the valve block 33. Subsequently, the chip 35, driven by the chip holder, moves upward, pressing the valve block 33 to seal and achieve pressure control. The valve block 33 is equipped with high-voltage electrodes that contact and conduct electricity with the reagent liquid to achieve electrophoresis voltage control.

[0057] The sample unit 2 continues to move the sample holder 23, inserting the capillary of the chip 35 into the standard centrifuge tube 24, extracting the standard for calibration. The capillary is then sequentially inserted into the preset wells of the sample plate 22 to be tested. The negative pressure draws the sample liquid to be tested into the chip 35. Subsequently, the sample holder 23 continues to move, aligning the buffer solution with the capillary. The capillary is then inserted into the buffer solution, soaking the capillary. The instrument performs the electrophoresis process analysis according to the preset logic, completing one analysis process.

Claims

1. A chip-type capillary electrophoresis instrument, comprising a chip and an optical detection module; characterized in that: The chip-type capillary electrophoresis instrument also includes: A sample unit, comprising a sample well plate and a first driving module, wherein the first driving module is used to move the sample well plate in three dimensions; An electrophoresis unit, comprising a first bracket, a supporting seat, and a second driving module, wherein the chip is disposed on the supporting seat, and the second driving module is used to move the supporting seat in two dimensions, wherein the supporting seat is disposed on the upper side of the sample well plate; a third driving module, configured to drive the optical detection module; The sample unit, the electrophoresis unit, the optical detection module and the third driving module are arranged in the housing, and the front side of the housing has an opening allowing the sample well plate and the supporting seat to pass through.

2. The chip-type capillary electrophoresis instrument according to claim 1, characterized in that: The three-dimensional movement includes forward and backward movement, up and down movement, and left and right movement, and the two-dimensional movement includes forward and backward movement and up and down movement.

3. The chip-type capillary electrophoresis instrument according to claim 1, characterized in that: A front door is provided on the front side of the housing for controlling the opening and closing of the opening.

4. The chip-type capillary electrophoresis instrument according to claim 1, characterized in that: A buffer centrifuge tube and a standard centrifuge tube are arranged on the side of the sample well plate.

5. The chip-type capillary electrophoresis instrument according to claim 4, characterized in that: The sample holder is arranged on the first driving module, and the sample well plate, the buffer centrifuge tube and the standard centrifuge tube are arranged on the sample holder.

6. The chip-type capillary electrophoresis instrument according to claim 1, characterized in that: The second driving module includes a vertical guide rail, a first guide rail and a motor. The first guide rail is arranged on the second bracket and extends in the front-to-back direction. The bearing seat is arranged on the first guide rail. The second bracket is arranged on the vertical guide rail and moves up and down under the drive of the motor. The vertical guide rail is arranged on the first bracket.

7. The chip-type capillary electrophoresis instrument according to claim 6, characterized in that: The valve group and the valve group adapter block are arranged on the upper side of the first bracket.

8. The chip-type capillary electrophoresis instrument according to claim 1, characterized in that: The optical detection module includes an excitation light path and a fluorescence detection light path. On the excitation light path, the excitation light emitted by the light source passes through a collimating lens and is then reflected by a dichroic mirror and a reflector in sequence. The reflected light passes through a first converging lens and is focused on the channel of the chip. On the fluorescence detection light path, the fluorescence excited in the channel passes through the first converging lens and is then reflected by the reflector. The reflected light passes through the dichroic mirror and the second converging lens in sequence and is received by the detector.

9. The chip-type capillary electrophoresis instrument according to claim 8, characterized in that: The optical detection module further includes a focusing light path, on which the fluorescence passing through the dichroic mirror is reflected by the beam splitter, and the reflected light passes through the imaging lens and is received by the second detector.

10. The chip-type capillary electrophoresis instrument according to claim 8, characterized in that: The fluorescent light passes through the dichroic mirror, the beam splitter and the second converging lens in sequence.

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