CN100427923C - Multifunctional chip detection device - Google Patents

Abstract

The present invention relates to a multifunctional chip detecting device which comprises a multifunctional chip detecting device frame, a chip platform for holding the chip, a light path detecting module, a light path inversion mechanism and a control interface system. When the detecting light path is above the chip platform in a photoelectric detecting module, and a reflection mirror of a light path switch is in the light path, the co-focusing scanning operation of the array chip can be accomplished. When the detecting light path is below the chip platform in the photoelectric detecting module, and the reflection mirror of the light path switch is in the light path, the laser-induced fluorescence detection of a micro flow control chip can be accomplished. When the detecting light path is above the chip platform in the photoelectric detecting module, and the reflection mirror of the light path switch is removed from the light path, the CCD scanning operation of the array chip can be accomplished. The present invention has wide application range and flexible detecting light path adjustment, and moreover, the data processing operation can be automatically completed by a computer.

Description

Multifunctional chip detection device

technical field

The invention relates to biochips for life sciences, medicine, and analytical chemistry, in particular to a multifunctional chip detection device, which is equipped with three types of microfluidic chip laser-induced fluorescence detection, array chip laser confocal scanning, and array chip CCD scanning. Function.

Background technique

Biochip is a product with great characteristics of the times in the high-tech field in recent years, and belongs to the comprehensive interdisciplinary field of molecular biology, physics and microelectronics. Biochips are widely used in life sciences, medicine, environmental monitoring, food industry, scientific research, biosensors and other fields, and integrate various biochemical reaction processes in these fields to realize the detection of biological macromolecules, proteins, microorganisms, etc. Efficient and fast testing and analysis of biologically active substances.

Laser-induced fluorescence detection devices include microfluidic chip analyzers produced by Albert Corporation in Canada, 2100 bioanalyzers produced by Angelon Corporation, etc. The basic principle is that the laser light generated by the laser passes through a filter and becomes approximately monochromatic light; The monochromatic light passes through the half-mirror and then irradiates into the micropipe of the chip through the objective lens; the fluorescent substance in the pipe excites the fluorescence of a certain wavelength after obtaining energy under the irradiation of the laser. Then, the excited fluorescence passes through the objective lens and half-mirror, and after transmission, the light of the non-exciting light wavelength is filtered out by the filter, and the exciting light is collected by the photomultiplier tube through the aperture, and the optical signal is transformed into into electrical signals and processed by a computer.

Laser scanning confocal microscope is a new type of analytical instrument that came out in the 1980s. Due to its high resolution, high sensitivity and high magnification, it can perform various functional measurements and analyzes at the molecular level, and has become an important tool for analysis. , The laser scanning confocal microscope is a new type of microscope formed by configuring a laser light source, a scanning device, a conjugate focusing device and a detection system on the basis of a microscope. The products mainly come from Bio-Rad and Meridian companies in the United States, and Zeiss and Leica companies in Germany.

Compared with the laser confocal chip scanner, the array chip CCD scanner has a simpler structure. The fluorescence generated by the biological chip under the excitation of the monochromatic light filtered by the excitation narrow-band interference filter is captured and imaged on the CCD chip by the camera lens through the narrow-band interference filter in front of the CCD lens. The image signal is directly transmitted to the image card by the CCD camera and processed directly by the computer. CCD can only read images at one excitation wavelength at a time. For chips labeled with multicolor fluorescent dyes, the filter and excitation light source need to be replaced. Since the CCD chip scanner reads the entire chip at the same time, there is no need to move the chip platform.

The instruments with the above functions only have a single function. In order to realize different chip operations, it is often necessary to purchase these instruments at the same time.

Contents of the invention

The purpose of the present invention is to overcome the above-mentioned shortcomings in the prior art. The present invention provides a multifunctional chip detection device, which should have three functions of confocal scanning, CCD scanning and laser-induced fluorescence detection of array chips. It has a Multi-purpose machine features.

Technical scheme of the present invention is as follows:

A multifunctional chip detection device includes a frame and a chip platform, which also includes:

① The detection light path module is a module with a fixed detection light path. The half-mirror is placed at 45° with the above-mentioned light beam, and the reflected light beam direction of the half-mirror is an objective lens, and the light beam passing through the objective lens group is directed to the chip platform, and the laser fluorescent light beam reflected by the chip passes through the said chip platform. A half-mirror, in the transmitted light direction is a switch and a CCD detector with a reflector, and on the reflected light path of the light path switch is a second optical filter, a lens, an aperture and a photomultiplier tube in sequence ;

② Optical path inversion mechanism, the optical path inversion mechanism is fixed on the frame, composed of outer shaft, inner shaft, ring arm and inner shaft and outer shaft fixing mechanism, the ring arm is fixed on the inner shaft One end of the inner shaft, the other end of the inner shaft is horizontally and coaxially sleeved in the bearing of the horizontal inner cavity of the outer shaft, the ring arm fixes the detection optical path module, the inner shaft and the outer shaft There is also a fixing mechanism between the shafts. In the case of manual operation, the inner shaft can slide in the horizontal direction in the inner cavity of the outer shaft, and can rotate 360° around the horizontal axis, driving the ring arm and its detection optical path module to surround The chip platform rotates, and when the object environment group is aligned with the chip of the chip platform, the relative position of the inner shaft and the outer shaft is locked by the fixing mechanism;

3. control interface system: the output of the photomultiplier tube passes through the filter circuit, the amplifier circuit, and the analog-to-digital converter A/D to the single-chip microcomputer; the instruction for controlling the gain of the photomultiplier tube sent by the computer passes through the single-chip microcomputer and the fourth digital-to-analog converter D/A is sent to the photomultiplier tube; the CCD detector is connected to the computer through the image acquisition card; the single-chip microcomputer is connected to the computer through the RS232 interface; the instruction of the control chip platform movement sent by the computer is respectively through the first digital-to-analog conversion through the single-chip microcomputer The device D/A and the second digital-to-analog converter D/A are sent to the X-axis motor and the Y-axis motor that control the movement of the platform to drive the movement of the chip platform; The converter D/A is sent to the focusing motor to adjust the focal length of the objective lens group.

The light source is composed of a white light source and a laser light source with the same optical axis, and the laser light source can be replaced according to needs in order to select a suitable working wavelength.

All the optical components of the detection optical path module are arranged in corresponding slots, and the slots have mounting and dismounting components for corresponding optical components.

The objective lens group and its support are connected through threads, and the thread rotation is controlled by a focusing motor to adjust the focal length of the objective lens group.

The optical path switching switch is an axis-rotating toggle switch or a parallel-moving switch.

The diaphragm aperture of the diaphragm has an adjustment mechanism.

The moving precision of the chip platform is better than 100 μm.

The computer has a data collection and processing program.

The filter of the output signal of the photomultiplier tube in the photodetection module adopts a second-order RC low-pass filter.

The fixing mechanism of the optical path inversion mechanism is a tightening bolt that penetrates the inner shaft from the outer shaft.

Technical effect of the present invention:

The laser light source in the photoelectric detection module of the present invention can be replaced and selected according to the laser wavelength required by the object to be measured. The wavelength of the device of the present invention has a wider range of use and is flexible to use;

All the optical lenses in the detection optical path of the photoelectric detection module in the present invention are placed in the corresponding slots, which can be replaced at any time according to the needs, and the positions are adjustable, which improves the detection flexibility of the device;

The focal length of the objective lens group is adjustable; the aperture of the diaphragm is adjustable, and the fine-tuning range is 2 μm to 28 μm;

The detection optical path in the photoelectric detection module is above the chip platform, and when the reflector of the optical path switching switch is in the optical path, the confocal scanning of the array chip can be completed;

When the detection optical path in the photoelectric detection module is below the chip platform, and the reflector of the optical path switching switch is in the optical path, the laser-induced fluorescence detection of the microfluidic chip can be completed;

The detection optical path in the photoelectric detection module is above the chip platform, and when the reflector of the optical path switching switch is moved out of the optical path, the CCD scanning of the array chip can be completed;

The invention has wide application range, flexible adjustment of detection optical path, and automatic completion of data processing by computer.

Description of drawings

Fig. 1 is the principle block diagram of the optical path of the detection optical path module of the device of the present invention;

Fig. 2 is the computer control interface schematic diagram of device of the present invention;

Fig. 3 is a schematic diagram of an optical path inversion mechanism of the device of the present invention;

In the picture:

1-detection optical path module; 101-light source; 102-first filter;

103-half mirror; 104-objective lens group; 105-optical path switch; 106-second filter;

107-lens; 108-aperture; 109-photomultiplier tube; 110-CCD detector;

11-optical path inversion mechanism; 111-fixing mechanism; 112-external shaft;

113-inner shaft; 114-circular arm;

2-filter circuit; 3-amplification circuit;

4-computer; 41-image acquisition card; 42-RS232 interface;

5-converter; 51-the first digital-to-analog converter D/A; 52-the second digital-to-analog converter D/A;

53 - the third digital-to-analog converter D/A; 54 - the fourth digital-to-analog converter D/A;

55-analog-to-digital converter A/D;

6-drive motor; 61-X-axis motor; 62-Y-axis motor; 63-focus motor;

7-chip platform; 8-biological chip; 9-single-chip microcomputer.

Detailed ways

The present invention will be further described below in conjunction with accompanying drawings, but the protection scope of the present invention should not be limited thereby.

As shown in Fig. 1 to Fig. 3, the present invention is a kind of multifunctional chip detection device, and its composition comprises:

A frame and a chip platform 7 also include:

① Detection optical path module 1 (as shown in Figure 1) is a template for fixedly setting the detection optical path. Sheet 102 and half-mirror 103, this half-mirror 103 is placed at 45° with the above-mentioned light beam, and the reflected light beam direction of this half-mirror 103 is objective lens group 104, passes through the light beam of this objective lens group 104 Pointing to the chip platform 7, the fluorescent light beam reflected by the chip 8 passes through the half mirror 103, and in the direction of the transmitted light is an optical path switching switch 105 and a CCD detector 110 with a reflector, in the On the reflection optical path of the optical path switching switch 105 are the second optical filter 106, the lens 107, the diaphragm 108 and the photomultiplier tube 109 in sequence;

② Optical path inversion mechanism 11 (as shown in Figure 3), this optical path inversion mechanism 11 is fixed on the described frame, by the fixing mechanism of outer shaft 112, inner shaft 113, ring arm 114 and inner shaft 113 and outer shaft 112 111, the ring arm 114 is fixed on one end of the inner shaft 113, and the other end of the inner shaft 113 is horizontally and coaxially sleeved in the bearing of the horizontal inner cavity of the outer shaft 112, so Said circular arm 114 fixes said detection optical path module 1, said inner shaft 113 and said outer shaft 112 are also provided with fixing mechanism 111, in the case of manual operation, said inner shaft 113 is in the inner cavity of outer shaft 112 It can slide along the horizontal direction and rotate 360° around the horizontal axis to drive the ring arm 114 and its detection optical path module 1 to rotate around the chip platform 7. When the object environment group 104 is aligned with the chip of the chip platform 7, The relative position of the inner shaft 113 and the outer shaft 112 is locked by the fixing mechanism 111;

3. control interface system (as shown in Figure 2): the output of described photomultiplier tube 109 passes filter circuit 2, amplifying circuit 3, analog-to-digital converter A/D55, to single-chip microcomputer 9; The control photomultiplier tube 109 that computer 4 sends The command of the gain is sent to the photomultiplier tube 109 through the single-chip microcomputer 9 and the fourth digital-to-analog converter D/A54; the CCD detector 110 is connected with the computer 4 through the image acquisition card 41; the single-chip microcomputer 9 is connected with the computer through the RS232 interface 42 4 are connected; the instruction of the control chip platform 7 movement sent by computer 4 is sent to the X-axis motor 61, The Y-axis motor 62 drives the movement of the chip platform 7; the instruction for adjusting the focal length of the objective lens group 104 sent by the computer 4 is sent to the focusing motor 63 through the single-chip microcomputer 9 through the third digital-to-analog converter D/A53, to adjust the focal length of the objective lens group 104 .

The light source 101 is composed of a white light source and a laser light source with the same optical axis, and the laser light source can be replaced according to needs in order to select a suitable working wavelength.

All the optical components of the detection optical path module 1 are arranged in corresponding slots, and the slots have mounting and dismounting components for corresponding optical components.

The objective lens group 104 and its bracket are connected by threads, and the thread rotation is controlled by a focusing motor to adjust the focal length of the objective lens group.

The optical path switching switch 105 of the reflector in the photoelectric detection module 1 is a rotary toggle switch around an axis or a parallel movement switch.

The diaphragm aperture of the diaphragm 108 has an adjustment mechanism.

The moving precision of the chip platform 7 is better than 100 μm.

Described computer 4 has data acquisition processing program; Described single-chip microcomputer 9 is 89C51 single-chip microcomputer.

The filter 2 of the output signal of the photomultiplier tube 109 adopts a second-order RC low-pass filter.

The fixing mechanism 11 of the optical path inversion mechanism 11 is a tightening bolt that passes through the inner shaft 113 from the outer shaft 112 .

The device of the present invention has three functions:

1. Laser-induced fluorescence detection of microfluidic chips, the procedure is as follows:

1. Adjust each component of the detection optical path module 1 in the multifunctional chip detection device of the present invention as required;

② Manually place the position of the detection optical path module 1 under the chip platform 7;

3. send the instruction of adjusting photomultiplier tube 109 gains by computer 4, send single-chip microcomputer 9 through RS232 interface 42, adjust the gain of photomultiplier tube through the 4th digital-to-analog converter 54;

4. Reset the reflector of the optical path switching switch 105, the laser light source of the light source 101 sends out the laser light of a specific wavelength, which is irradiated on the chip platform 7 through the first optical filter 102, the half-transparent mirror 103 and the reflection through the objective lens group 104 successively. In the micropipe of the micro-control flow chip 8, the substance in the micropipe generates fluorescence under the action of excitation light, and the fluorescence is reflected by the objective lens group 104, the half-transparent mirror 103 and the optical path switch 105 in turn, and then passed through The second optical filter 106 filters light to eliminate stray light outside the fluorescence, and the fluorescence passes through the lens 107 and the aperture 108, and is received by the photomultiplier tube 109, and the generated electrical signal is filtered by the filter circuit 2 and then amplified by the amplifier circuit 10. The amplified signal is converted into a digital signal by the analog-to-digital converter 55 and sent to the single-chip microcomputer 89C519 for processing, and then sent to the computer 4 through the RS232 interface 42. The computer 4 runs the data acquisition and processing program to complete the fluorescence detection of the micropipe in the micro-control flow chip 8 to be tested.

2. Laser confocal scanning of the array chip, the procedure is as follows:

1. Adjust each component of the detection optical path module 1 in the multifunctional chip detection device of the present invention as required;

② Manually place the detection optical path module 1 above the chip platform 7;

3. send the instruction of regulating photomultiplier tube 109 gains by computer 4, send single-chip microcomputer 89C519 through RS232 interface 42, adjust the gain of photomultiplier tube 109 through the 4th digital-to-analog converter 54;

④The reflector of the optical path changeover switch 105 is reset;

5. according to the specification of array chip, computer 4 sends the instruction of speed and the distance that control chip platform 7 moves along X, Y axis, sends into single-chip microcomputer (89C51) 9 to process through RS232 interface 42, through the first digital-to-analog converter 51 and The second digital-to-analog converter 52 generates pulse signals to control the X-axis and Y-axis servo motor drivers to drive the movement of the X-axis and Y-axis servo motors, and drives the chip platform 7 to move through the chip platform 7 moving mechanism 62 .

6. During the movement of the chip platform 7, the laser light source of the light source 101 emits laser light of a specific wavelength, which is irradiated on the array on the chip platform 7 through the first optical filter 102, the half mirror 103 and reflection through the objective lens group 104. Chip 8, the material in this array chip produces fluorescence under the action of excitation light, and this fluorescence is reflected by the reflector of objective lens group 104, half-transparent mirror 103, optical path switching switch 105, and is filtered by second filter sheet 106. Light, eliminate the stray light outside the fluorescent light, the fluorescent light is received by the photomultiplier tube 109 through the lens 107 and the diaphragm 108, and the generated electric signal is passed through the filter circuit 2 and the amplifier circuit 10, and the amplified signal is converted by the analog-to-digital converter 55 After the digital signal is sent to the single chip microcomputer (89C51) 9 for processing, it is sent to the computer 4 through the RS232 interface 42, and the computer 4 runs the data acquisition and processing program to complete the laser confocal scanning of the array chip to be tested.

3. CCD scanning of the array chip

1. Adjust each component of the detection optical path module 1 in the multifunctional chip detection device of the present invention as required;

② Manually place the detection optical path module 1 above the chip platform 7;

③ Move the optical path switch to move the reflector 105 out;

4. The laser light source of light source 101 sends out the laser light of specific wavelength, through first optical filter 102, half mirror 103 reflection, irradiates the array chip 8 that is positioned on the chip platform 7 through objective lens group 104, the material in this array chip is excited Under the effect of light, produce fluorescence, this fluorescence passes objective lens group 104, half mirror 103, is received by CCD110 by optical path switching switch, is sent to computer 4 by image acquisition card 41, and computer 4 runs data collection and processing program, completes treatment CCD scanning of array chips.

It can be seen from the above that the device of the present invention provides a multi-functional chip detection device, which has three functions of confocal scanning, CCD scanning and laser-induced fluorescence detection of array chips, and has the characteristics of one machine with multiple functions.

Claims (10)

1, a kind of multifunction chip-detecting apparatus comprises a frame and the chip platform of placing for chip (7), it is characterized in that also comprising:

1. detect light path module (1), be one to fixedly install the module that detects light path, its light path is constructed as follows: a light source (101), the working direction of sending light beam along this light source (101) with optical axis set gradually first optical filter (102) and semi-transparent semi-reflecting lens (103), this semi-transparent semi-reflecting lens (103) and the placement at 45 of above-mentioned light beam, folded light beam direction at this semi-transparent semi-reflecting lens (103) is objective lens (104), see through the described chip platform of this objective lens (104) beam-pointing (7), fluorescent light beam by the chip reflection sees through described semi-transparent semi-reflecting lens (103), transmitted light direction at this semi-transparent semi-reflecting lens (103) is light path change-over switch (105) and the ccd detector (110) with catoptron, is second optical filter (106) successively on the reflected light path of described light path change-over switch (105), lens (107), diaphragm (108) and photomultiplier (109);

2. light path invert mechanism (11), this light path invert mechanism (11) is fixed on the described frame, by outer shaft (112), interior axle (113), annular arm (114) and interior axle (113) are formed with the fixed mechanism (111) of outer shaft (112), described annular arm (114) is fixed on an end of described interior axle (113), should in axle (113) other end level and be set in coaxially in the bearing of horizontal cavity of described outer shaft (112), described annular arm (114) is fixed described detection light path module (1), also be provided with fixed mechanism (111) between axle (113) and the outer shaft (112) in described, under manual situation, axle (113) along continuous straight runs in the inner chamber of outer shaft (112) slides in described, or around 360 ° of rotations of transverse axis, drive annular arm (114) and detect light path module (1) around described chip platform (7) rotation, aim at the chip of chip platform (7) when objective lens (104) after, described interior axle (113) is locked by described fixed mechanism (111) with the relative position of outer shaft (112);

3. control interface system: the output of described photomultiplier (109) through filtering circuit (2), amplifying circuit (3), modulus converter A/D (55) to single-chip microcomputer (9); The instruction of the gain of the control photomultiplier (109) that computing machine (4) sends sends to photomultiplier (109) through single-chip microcomputer (9) and the 4th digital to analog converter D/A (54); Described ccd detector (110) links to each other with computing machine (4) through image pick-up card (41); Single-chip microcomputer (9) links to each other with computing machine (4) through RS232 interface (42); The instruction of control chip platform (7) motion that computing machine (4) sends sends to X-axis servomotor (61), the Y-axis servomotor (62) that control chip platform (7) moves, the motion of chip for driving platform (7) through the first data converter D/A (51) and the second digital-to-analogue piece parallel operation D/A (52) respectively through single-chip microcomputer (9); The instruction of adjustment objective lens (104) focal length that computing machine (4) sends sends to focusing servomotor (63) through single-chip microcomputer (9) through the 3rd digital to analog converter D/A (53), to adjust the focal length of objective lens (104).

2, multifunction chip-detecting apparatus according to claim 1 is characterized in that described light source (101) is made up of white light source and LASER Light Source with optical axis, and described LASER Light Source can be changed as required, so that select suitable operation wavelength.

3. multifunction chip-detecting apparatus according to claim 1 is characterized in that all optical elements of described detection light path module (1) all are placed in the corresponding draw-in groove, and this draw-in groove has the loading and unloading member of respective optical element.

4. multifunction chip-detecting apparatus according to claim 1 is characterized in that described objective lens (104) and its support are by being threaded, by focusing servomotor (63) control screw thread rotation, to regulate the focal length of objective lens (104).

5. multifunction chip-detecting apparatus according to claim 1, the light path change-over switch (105) that it is characterized in that described catoptron is the element with logical light and reflected light function, it is toggle switch or the parallel movable switch of pivoting.

6. multifunction chip-detecting apparatus according to claim 1 is characterized in that the aperture of the diaphragm of described diaphragm (108) has adjusting mechanism.

7. multifunction chip-detecting apparatus according to claim 1 is characterized in that the mobile accuracy of described chip platform (7) is better than 100 μ m.

8. multifunction chip-detecting apparatus according to claim 1 is characterized in that described computing machine (4) has the data acquisition process program.

9. multifunction chip-detecting apparatus according to claim 1 is characterized in that the filtering circuit (2) of described photomultiplier (109) output signal adopts the Order RC low-pass filter.

10. according to each described multifunction chip-detecting apparatus of claim 1 to 9, the fixed mechanism (111) that it is characterized in that described light path invert mechanism (11) is one to penetrate the puller bolt of interior axle (113) by outer shaft (112).

Images