TWI409449B - Bio-detecting device with adjustable micro-concave mirror - Google Patents

Abstract

The invention relates to a biological testing apparatus containing an adjustable slightly concave mirror, which includes a cell chip, a laser device, a slightly concave mirror part, a control part and an inspection device; the cell chip provides a transparent structure in which a plurality of cells containing fluorescent compounds flow in the microfluidic channel along a flow direction; the channel width of the microfluidic channel is greater than the diameter of the cells; the laser device emits a laser light beam, which has a diameter greater than the channel width, toward the slightly concave mirror part; the control part is used for controlling and adjusting the surface curvature of the slightly concave mirror part and reflecting most of the laser light beam into a focused light beam which is focused and irradiated on the light irradiation position of the microfluidic channel. If cells are irradiated when passing through the light irradiation position by the focused light beam, the fluorescent compound is excited to generate strong fluorescence due to absorbing the strong light energy of the focused light beam, which will enhance the accuracy of said testing apparatus. Therefore, the invention has both the advantages and effects of greatly increasing accuracy of cell inspection and adjusting the focal length of the focused light beam.

Description

Biodetection device with adjustable micro concave mirror

The invention relates to a biological detecting device, in particular to a biological detecting device with an adjustable micro concave mirror, which has the functions of greatly improving the accuracy of cell detection and adjusting the focal length of the focused beam.

Referring to FIG. 8A, the conventional biological detecting device comprises a cell wafer 81, a laser device 82, a control portion 83 and a detecting device 84. The cell wafer 81 is provided with a plurality of cells 91 with fluorescent compounds. The flow channel 911 of the microchannel 811 flows for detection; the channel width W2 of the microchannel 811 is larger than the cell diameter D3 of the cell 91; and the control unit 83 controls the laser device 82 to emit a laser beam toward the microchannel 811. 821, the beam diameter D4 is greater than the flow path width W2; and the laser 91 is irradiated with the laser beam 821 to cause the fluorescent compound to absorb the light energy to emit fluorescence, thereby improving the accuracy of the detection by the detecting device 84.

The traditional structure produces the following deficiencies:

[1] The accuracy of cell detection is low. Suppose a conventional circular area of the laser beam is 785000μm ² (calculated beam diameter 1000μm), while the micro-channel is the area of laser beam strikes only 2500μm ² (50μm calculated in the flow channel width). The light energy in the laser beam representing a circular area of 785000 μm ² has an area of only 2500 μm ² (only The light energy left on the microchannel, the fluorescence of the fluorescent compound on the cell is bound to be limited (as shown in Figure B, the highest peak is at most 3.8mv, and the peak of the noise Up to 3~3.2mv, can't be quite clearly), plus the noise generated by external light interference, so that the detected result is sometimes confused by the fluorescence emitted by the cells, or the external light, affecting the accuracy of cell detection. degree.

[2] The position of the laser beam illumination cannot be adjusted. The conventional biological detecting device directly emits a laser beam directly toward the cell wafer by the laser device, and there is no adjustment device at all. Therefore, the position where the laser beam is irradiated on the cell wafer cannot be adjusted, and the position of the cell wafer cannot be installed. And change the direction of the laser beam at any time.

In view of this, it is necessary to develop a technique that can solve the above disadvantages.

It is an object of the present invention to provide a biodetection device having an adjustable micro concave mirror which has the advantages of greatly improving the accuracy of cell detection and adjusting the focal length of the focused beam. In particular, the problems to be solved by the present invention include problems such as low accuracy of cell detection and inability to adjust the position of laser beam irradiation.

A technical means for solving the above problems is to provide a biodetection device having an adjustable micro concave mirror, comprising: a cell wafer having a light transmissive structure having at least one microchannel for supplying a plurality of fluorescent compounds The cells flow in a flow direction in the fluid in the microchannel for detection; the microchannel has a first-order track width; each cell line has a cell diameter, the channel width is greater than the cell diameter; a laser The device is configured to emit a laser beam having a beam diameter, the beam diameter being greater than the channel width; a micro concave mirror portion having a central portion, a plurality of micro concave mirrors, and a plurality of microscopic And a virtual central axis; a plurality of micro concave mirrors are radially connected around the central portion, and the plurality of microactuators respectively control the plurality of micro concave mirrors to make the plurality of micro concave mirrors and the center The portion may change its surface curvature centered on the virtual central axis; a control portion for controlling the operation of the microactuator; and a detecting device located at the cell wafer a side for detecting the plurality of cells downwardly; thereby, when the microactuator controls to adjust a surface curvature of the central portion and the plurality of micro concave mirrors, the laser beam is irradiated to the central portion and the plurality a micro concave mirror reflects a focused beam and focuses upwardly on the illumination position of the microchannel. When the cell passes through the illumination position, the focused beam is illuminated, and the fluorescent compound is excited by absorbing the powerful light energy of the focused beam. The intensity of the detection device can be improved by the strong fluorescence; wherein the micro concave mirror portion comprises a reflective film deposited on the surface of a polycrystalline structure; the central portion and the plurality of micro concave mirror systems and the laser beam The system has an incident angle, and the central portion and the plurality of micro concave mirrors have a reflection angle with the focused beam; the incident angle is at the reflection angle; the microactuator is a piezoelectric microactuator .

The above objects and advantages of the present invention are not difficult to be selected from the following selected embodiments. A detailed understanding of the detailed description and the drawings is obtained.

The invention will be described in detail in the following examples in conjunction with the drawings:

The present invention is a biodetection device with an adjustable micro concave mirror. Referring to the first, second and third A diagrams, the invention comprises: a cell wafer 10 having a light transmissive structure with at least one microchannel 11 for use. For a plurality of cells 91 with fluorescent compounds in the fluid 911 in the microchannel 11, flow in a flow direction A (as shown in the fourth figure) for detection; the microchannel 11 has a first-class width W1; each of the cells 91 has a cell diameter D1, the channel width W1 being greater than the cell diameter D1; a laser device 20 for emitting a laser beam 21 having a beam a diameter D2, the beam diameter D2 is greater than the flow path width W1; a micro concave mirror portion 30 having a central portion 31, a plurality of micro concave mirrors 32, a plurality of microactuators 33, and a virtual central axis X; The micro concave mirror 32 is radially connected around the central portion 31. The plurality of microactuators 33 respectively control the plurality of micro concave mirrors 32, so that the plurality of micro concave mirrors 32 and the central portion 31 can be virtualized. The central axis X is centered to change its surface curvature; a control unit 40, for controlling the action of the microactuator 33; a detecting device 50 is located above the cell wafer 10 for detecting the plurality of cells 91 downward; Thereby, when the microactuator 33 controls to adjust the surface curvature of the central portion 31 and the plurality of micro concave mirrors 32, the laser beam 21 is irradiated to the central portion 31 and the plurality of micro concave mirrors 32 to reflect A focused beam 30A is focused upwardly to the illumination position P1 of the microchannel 11 (as shown in the fourth figure), and when the cell 91 passes through the illumination position P1, the focused beam 30A is irradiated, and the fluorescent compound is absorbed by the fluorescent compound. Focusing on the strong light energy of the beam 30A to excite strong fluorescence, the accuracy of the detection by the detecting device 50 can be improved (as shown in FIG. 3B); wherein the micro concave mirror portion 30 is included in a polycrystalline structure 30B. a reflective film 30C is deposited on the surface; the central portion 31 and the plurality of micro concave mirrors 32 have an incident angle θ 1 (and θ 3 ) between the laser beam 21; and the central portion 31 and the plurality of micro concave mirrors 32 There is a reflection angle θ 2 (and θ 4) between the focused beam 30A, and the incident angle θ 1 (and θ 3) is equal to the reflection angle θ 2 (and θ 4); the microactuator 33 is It is a piezoelectric microactuator.

In practice, the cell wafer 10 is made of glass.

The micro concave mirror portion 30 has a mirror portion diameter D5 (about 800 μm).

This flow path width W1 is 50 μm.

The cell diameter D1 is between 6 um (eg, nucleus) ~ 30 μm (most eukaryotic animal cells).

The beam diameter D2 is 1000 μm.

Referring to FIG. 6A, the thermal microactuator is composed of two thermal expansion coefficient structures 33A, 33B combined with a warming device 33C. One end of the two thermal expansion coefficient structures 33A, 33B is connected to the corresponding micro concave mirror 32, and the other end Then, the heating device 33C is connected, and when the heating device 33C applies an operating temperature of 0 to 350 ° C to the two thermal expansion coefficient structures 33A, 33B (as shown in FIG. 6B), the two thermal expansion coefficient structures 33A, 33B can be The surface curvature of the central portion 31 and the plurality of micro concave mirrors 32 is adjusted such that the focal length of the focused beam 30A varies from 0 to 2400 μm.

Referring to FIG. 7A, the piezoelectric microactuator is composed of a piezoelectric structure 33D coupled with a power supply structure 33E. One end of the piezoelectric structure 33D is coupled to the corresponding micro concave mirror 32, and the other end is coupled to the power supply structure 33E. The power supply structure 33E applies an operating voltage of 0 to 150 V to the piezoelectric structure 33D (as shown in FIG. 7B), and the piezoelectric structure 33D can adjust the surface curvature of the central portion 31 and the plurality of micro concave mirrors 32 to focus the beam. The focal length of 30A varies between 300 and 425 μm.

The operation mode of the present invention is as follows: the laser device 20 is activated to illuminate a laser beam 21 toward a central portion 31 of the micro concave mirror portion 30 and a plurality of micro concave mirrors 32, and the microactuator 33 is controlled. To adjust the surface curvature of the plurality of micro concave mirrors 32 and the central portion 31, and to reflect a focused beam 30A (as shown in the fifth figure, it is assumed that the central portion 31 and the plurality of micro concave mirrors 32 are respectively adjusted to be the first, second, and third. The surface curvatures S1, S2 and S3 respectively reflect the focused beam 30A and are irradiated at the illumination position P1, the second position P2 and the third position P3, wherein the illumination position P1 is irradiated on the microchannel 11 of the cell wafer 10) focused illumination At the illumination position P1 of the microchannel 11, when the cell 91 with the fluorescent compound flows through the illumination position P1 and is irradiated by the focused beam 30A, the fluorescent compound excites strong fluorescence, and the detecting device 50 detects only Cells 91 that emit intense fluorescence produce a fairly high amplitude signal.

In more detail, the circular area of the laser beam 21 is 785000 μm ² (calculated as a beam diameter of 1000 μm), and the circular area of the micro concave mirror portion 30 is 502400 μm ² (calculated as a mirror portion diameter of 800 μm), and it is assumed that the micro flow path 11 is focused. The area irradiated by the light beam 30A was 2,500 μm ² (calculated as a flow path width of 50 μm). Representative 785000μm circular area 21 of laser beam ² has at least 30 micro-concave mirrors 502400μm ² is reflected and irradiated onto an area of 2500 m ² micro channel 30A, and this area of 2500 m ² i.e. having a circular area of the laser beam 502400μm ² 21 The light energy can cause the fluorescent compound on the cell 91 to excite strong fluorescence, so that the detecting device 50 can detect the amplitude signal of up to 8 mv as shown in the third B picture, and the amplitude signal of the external light interference is only 2 mv at most. However, the difference is 4 times, quite obvious, and easy to interpret.

Of course, even if the cell wafer 10 is located within the range in which the laser beam 21 is directly irradiated, the detection result is not affected.

The advantages and effects of the present invention can be summarized as follows:

[1] can greatly improve the accuracy of cell detection. According to the present invention, a micro-concave mirror portion (circular area of 502400 μm ² ) is disposed to reflect a large portion of light of a laser beam (round area of 785000 μm ² ) (502400 μm ² in 785000 μm ² ), and is irradiated to the micro flow path to make the micro flow path ² 2500μm illuminated area having a circular area 502400μm energy of the laser beam ^2, when the strong fluorescence of the cells with a fluorescent compound having a strong focusing light energy beam is irradiated, i.e. compounds which stimulate fluorescence ( The higher the luminous energy of the illumination, the stronger the fluorescence, so that the detection device detects the intense fluorescence of the cells and generates a strong amplitude signal (up to 8 mv), thereby improving the accuracy of the cell detection (the sensitivity is increased by 350%).

[2] The focal length of the focused beam can be adjusted. The micro-concave mirror part of the invention consists of a central part, a plurality of micro concave mirrors and a plurality of microactuators, and controls a plurality of microactuators to adjust the surface curvature of the plurality of micro concave mirrors and the central part, thereby adjusting the focus. The focal length of the beam can be adjusted to the focal length of the actual cell wafer.

The present invention has been described in detail with reference to the preferred embodiments of the present invention, without departing from the spirit and scope of the invention.

10, 81‧‧‧ cell wafer

11, 811‧‧‧ micro-channel

20, 82‧‧ ‧ laser device

21, 821‧‧ ‧ laser beam

30‧‧‧Micro concave mirror

30A‧‧‧focus beam

30B‧‧‧Polysilicon structure

30C‧‧‧Reflective film

31‧‧‧ Central Department

32‧‧‧micro concave mirror

33‧‧‧Micro Actuator

33A, 33B‧‧‧ Thermal expansion coefficient structure

33C‧‧‧heating device

33D‧‧‧Piezoelectric structure

33E‧‧‧Power supply structure

40, 83‧‧‧Control Department

50, 84‧‧‧Detection device

91‧‧‧ cells

911‧‧‧ fluid

X‧‧‧Virtual Center Axis

A‧‧‧flow direction

W1, W2‧‧‧ flow path width

D1, D3‧‧‧ cell diameter

D2, D4‧‧‧ beam diameter

D5‧‧‧Mirror diameter

P1‧‧‧Light position

P2‧‧‧ second position

P3‧‧‧ third position

θ 1 , θ 3‧‧‧ incident angle

θ 2, θ 4‧‧‧ reflection angle

S1‧‧‧ first surface curvature

S2‧‧‧second surface curvature

S3‧‧‧ Third surface curvature

The first figure is a schematic diagram of an application example of the present invention

The second figure is a schematic diagram of the main structure of the present invention.

The third A diagram is an enlarged schematic view of a part of the structure of the second figure

The third B picture is the waveform diagram of the detection cell of the third A picture

The fourth figure is a schematic diagram of the focused beam irradiating cells and detecting cells of the present invention.

The fifth figure is a schematic diagram of the adjustment operation of the micro concave mirror portion of the present invention.

Figure 6A is a schematic view showing a first application example of the microactuator of the present invention

Figure 6 is a graph of temperature and focal length of Figure 6A.

Figure 7A is a schematic view showing a second application example of the microactuator of the present invention

Figure 7 is a graph of the voltage and focal length of Figure 7A.

Figure 8A is a schematic diagram of a conventional biological detection device

Figure 8 is a waveform diagram of the cells detected in Figure 8A.

10. . . Cell wafer

11. . . Microchannel

20. . . Laser device

twenty one. . . Laser beam

30. . . Micro concave mirror

30A. . . Focus beam

31. . . Central department

32. . . Micro concave mirror

40. . . Control department

50. . . Testing device

91. . . cell

911. . . fluid

X. . . Virtual central axis

W1. . . Runner width

D1. . . Cell diameter

D2. . . Beam diameter

D5. . . Mirror diameter

Claims (2)

A biodetection device with an adjustable micro concave mirror includes: a cell wafer having a light transmissive structure having at least one microchannel for supplying a plurality of cells with a fluorescent compound in a fluid in the microchannel Flowing in a flow direction for detection; the microchannel has a first-order track width; each cell line has a cell diameter, the channel width is greater than the cell diameter; and a laser device is used to emit a thunder a beam having a beam diameter greater than the channel width; a micro concave mirror portion having a central portion, a plurality of micro concave mirrors, a plurality of microactuators, and a virtual central axis; A plurality of micro concave mirrors are radially connected around the central portion, and the plurality of microactuators respectively control the plurality of micro concave mirrors such that the plurality of micro concave mirrors and the central portion are centered on the virtual central axis And changing the surface curvature; a control portion for controlling the movement of the microactuator; a detecting device located above the cell wafer for detecting the plurality of fines downward Thereby, when the microactuator controls to adjust the surface curvature of the central portion and the plurality of micro concave mirrors, the laser beam is irradiated to the central portion and the plurality of micro concave mirrors to reflect a focused beam, and Focusing the illumination position of the microchannel upward, when the cell is irradiated by the focused beam through the illumination position, and the fluorescent compound is excited by absorbing the powerful light energy of the focused beam The intensity of the detection device can be improved by the strong fluorescence; wherein the micro concave mirror portion comprises a reflective film deposited on the surface of a polycrystalline structure; the central portion and the plurality of micro concave mirror systems and the laser beam The system has an incident angle, and the central portion and the plurality of micro concave mirrors have a reflection angle with the focused beam; the incident angle is at the reflection angle; the microactuator is a piezoelectric microactuator . The biodetection device with an adjustable micro concave mirror according to claim 1, wherein: the flow channel width is 50 μm; the cell diameter is between 6 and 20 μm; and the beam diameter is 1000 μm; The micro concave mirror portion has a mirror portion diameter of 800 μm.