TWI397686B - Optical analyzing apparatus and method for determination of multiple metabolites - Google Patents

Description

Multi-light source biochemical detecting device and method

The invention relates to a biochemical detecting device and method, in particular to a multi-light source biochemical detecting device and method.

Generally, commercially available biochemical detection devices are difficult to carry because of large blood collection, high price, and are not easy to carry. The main reason is that the designed optical device design and mechanical structure of the detection device are too complicated and costly. For example, the detection device disclosed in U.S. Patent Nos. 5,122,284, 6,668, 805, and 6,723, 287, the fluid cartridge is a DISC type and the transmission system is coaxial, and the optical system of the fluid cartridge, the excitation light source and the optical detector are designed. Institutional technology is more complicated and the production cost is higher. In addition, U.S. Patent No. 6,589, 155 and U.S. Patent No. 7,267,795 disclose a non-coaxial detection device, but the structure is too complicated, the manufacturing cost is high, and the biochemical detection function performed is different from the present case. Moreover, the fluid cartridge used in the US Pat. No. 6,051,163 is a square disk-shaped detection method, and the structure is relatively complicated and has no function of blood centrifugation.

Therefore, the design of the device with low blood collection, low price and easy to carry and easy to operate is the engine of the invention, and the main function of the device is applied to the calibration of various important physical organs, such as liver, kidney function and cardiovascular disease, suitable for Use in point-of-care and home environments.

The object of the present invention is to provide a multi-source biochemical detection device and method, which are suitable for collecting trace whole blood for separation and signal detection with fluorescence, cold light and absorption light reaction.

Further, another object of the present invention is to provide a multi-source biochemical detecting device that utilizes a non-coaxial motor transmission system to improve overall system space utilization and device function expandability.

The multi-source biochemical detecting device of the present invention is configured to analyze a sample contained in a cassette, and includes a motor driving unit, a cassette carrying unit, and a light source detecting system; the cassette carrying unit carries the cassette And having an opening, a first opening, and a second opening, wherein the motor driving unit drives the cassette carrying unit to rotate; the light source detecting system comprises a first light source, a second light source, and a first light detecting And a second photodetector, wherein the light beam from the first light source penetrates the sample in a straight line and is incident on the first photodetector via the first opening, and the light beam from the second light source passes through the opening After the sample is bent at an angle and incident on the second photodetector through the second opening, the optical energy of the sample is detected.

In an embodiment, the first photodetector and the second photodetector are located below the cassette carrying unit.

In an embodiment, the first opening and the second opening are both formed at the bottom of the cassette carrying unit.

In an embodiment, the first light source is located above the cassette carrying unit and the second light source is located on the side of the cassette carrying unit.

In an embodiment, the position of the first light source corresponds to the first opening; and the opening is formed on the side of the cassette carrying unit.

In an embodiment, the cassette carrying unit further has a third opening, and the multi-light source biochemical detecting device further includes a third photodetector disposed in a manner corresponding to the third opening; The three-photodetector is located below the cassette carrying unit and can be a photomultiplier tube module. In addition, the openings can be plural, and the positions of the openings are respectively corresponding to the first opening, the second opening, and the first Three openings correspond.

It should be understood that the angle between the first opening and the center of the cassette carrying unit and the line connecting the second opening to the center of the cassette carrying unit is 90 degrees.

In one embodiment, the light source detecting system further includes an objective lens and an optical filter respectively disposed upstream of the incident light beam of the second photodetector.

It should be understood that this angle is bent to 90 degrees, but it is not limited to 90 degrees and can be changed corresponding to the need.

In one embodiment, the motor drive unit includes a belt and a motor body, wherein the belt is coupled to the cassette carrying unit, and the motor body is coupled to the belt to drive the cassette carrying unit to rotate by the belt.

In an embodiment, the motor drive unit and the cassette carrying unit are coupled in a non-coaxial manner.

In one embodiment, the second light source is a semiconductor laser; further, the light source detecting system further includes a focusing lens disposed before the semiconductor laser to adjust the laser beam output from the semiconductor laser.

In an embodiment, the first light source is a light emitting diode.

In an embodiment, the cassette carrying unit further has a positioning hole, and the multi-light source biochemical detecting device further comprises a third light source and a positioning light detector, wherein the light beam from the third light source is incident through the positioning hole The positioning photodetector is used for rotational positioning as a cassette carrying unit.

In an embodiment, the multi-source biochemical detection device further includes a controller electrically connected to the motor driving unit and the light source detecting system.

The multi-source biochemical detection method of the present invention is used for analyzing a sample contained in a cassette, comprising the following steps: First, placing a cassette on a cassette carrying unit, wherein the cassette carrying unit has an opening and a a first opening, and a second opening; and then rotating the cassette carrying unit; thereafter, simultaneously injecting a first beam and a second beam into the sample, and the first beam passing through the sample is disposed in the cassette The first photodetector under the carrying unit detects, and the fluorescent light generated after the second beam passes through the sample is detected by a second photodetector disposed under the cassette carrying unit, wherein the first beam is linearly The sample is penetrated into the first photodetector via the first opening, and the second beam is incident at an angle through the opening, and is incident at the second photodetector via the second opening.

In an embodiment, the cassette carrying unit can be rotated by different numbers of rotations.

In one embodiment, the first beam is incident from the top of the cassette carrying unit to the sample and the second beam is incident from the side of the cassette carrying unit to the sample.

In one embodiment, the luminescence of the sample is detected by a third photodetector disposed below the cassette carrying unit.

As described above, the non-coaxial motor drive unit used in the present invention does not have a complicated system optical path and transmission mechanism design, so the production cost is low, the mass production is easy to be developed, and the mechanism for simultaneously detecting samples by multiple light sources is utilized to quickly provide biochemical multi-markers. A platform for simultaneous analysis. Moreover, due to the non-coaxial relationship between the cassette and the motor, the space under the cassette carrying unit becomes large, and the function expandability of the device is also improved. The overall system is easy to operate and small in size and suitable for development as a portable multi-source biochemical detection device.

Please refer to the first and sixth figures. The multi-source biochemical detecting device 1 of the embodiment of the present invention is configured to analyze a sample contained in a cassette 10, including a body 20, a motor driving unit 30, and a card. The load carrying unit 40, a light source detecting system 50, and a controller 60; wherein the cassette 10 is made of a transparent material and includes a plurality of separation chambers (not shown) for receiving samples therein.

The body 20 is a casing of the multi-light source biochemical detecting device 1. In the first figure, only the bottom of the casing is shown; the body 20 is provided with a first base 21, a second base 22, and a third base. 23, for positioning the motor drive unit 30, the cassette carrying unit 40, and the light source detecting system 50; in addition, it should be understood that in the first figure, in order to simplify the illustration, only the second base is represented in a schematic manner. 22 and the relationship between the cassette carrying unit 40, as for the way of connecting between the two can refer to Figure 2b.

The motor drive unit 30 includes a belt 31, a motor body 32, and a circular belt wheel 33, wherein one end of the belt 31 is coupled to the cassette carrying unit 40, and the other end is coupled to the circular belt wheel 33; the motor body 32 is disposed on the first base 21 of the body 20, and its axial center is combined with the circular belt wheel 33 to form a load to drive the belt 31 to rotate, and the circular belt pulley 33 and the cassette carrying unit 40 pass through the belt 31. The combination produces a transmission relationship, forming a non-coaxial motor drive system, which has the function of rotating the cassette 10, which is different from the common motor drive system of the conventional optical disc drive, and the motor main body 32 provides the cassette 10 for plasma. The high RPM speed required for separation from the blood cells and the source of the low RPM required for the detection of optical reaction changes in the target reactants (samples).

Referring to Figures 2a and 2b, the cassette carrying unit 40 includes a cassette carrying turntable 41, and a portion of the carrying mechanism and the Palin 42, wherein the cassette carrying turntable 41 carries the cassette 10 thereon, and the Palin 42 is Below the cassette carrying turntable 41, the cassette carrying turntable 41 is rotated via the belt 31, that is, the cassette carrying unit 40 is driven by the motor drive unit 30 in a non-coaxial manner.

Referring to FIG. 3, the cassette carrying turntable 41 has four openings 41a, a first opening 41b, a second opening 41c, a third opening 41d, a fourth opening 41e, and a positioning hole 41f. The first opening 41b, the second opening 41c, the third opening 41d, and the fourth opening 41e are formed at the bottom of the cassette carrying turntable 41, and the opening 41a is formed on the side of the cassette carrying turntable 41. .

As shown in Fig. 3, the angle between the first opening 41b and the center C of the cassette carrying turntable 41, and the line connecting the second opening 41c to the center C of the cassette carrying turntable 41 is 90. Degree, and the angle between the second opening 41c and the center C of the cassette carrying turntable 41, and the line connecting the third opening 41d and the center C of the cassette carrying turntable 41 is 90 degrees; The position of 41a corresponds to the first opening 41b, the second opening 41c, the third opening 41d, and the fourth opening 41e, respectively.

In detail, the number of the separation chambers of the cassette 10 may be four, and the positions thereof may correspond to the openings 41a of the side of the cassette carrying turntable 41, respectively, and the positions of the separating chambers directly correspond to the openings 41b, 41c, respectively. 41d, 41e; further, the four openings 41a on the side of the cassette carrying turntable 41 mainly allow the laser beam from the light source detecting system 50 to be incident on the separation chamber of the cassette 10 to excite the fluorescent reaction of the sample. And the four openings 41b, 41c, 41d, 41e directly below the separation chamber of the cassette 10 are mainly the first photodetector 53, the second photodetector 54, and the third of the light source detecting system 50. The photodetector 55 can detect the absorption of the sample, the reaction of the fluorescent light with the luminescent light source, which will be described in detail below.

In addition, it should be understood that the number of openings and openings is not limited to four, and may vary corresponding to the number of reaction chambers of the cassette 10; in addition, the positional relationship between the openings and the opening to the cassette carrying turntable The angle between the lines of the center C is not limited to 90 degrees, and may be changed corresponding to the need.

Referring to Figures 1 and 4, the multi-light source biochemical detecting device 1 further includes a positioning unit 70 having a third light source 71 and a positioning light detector 72, wherein the third light source 71 is disposed on the cassette carrying turntable 41. Above the positioning light detector 72 is disposed below the cassette carrying turntable 41; the light beam from the third light source 71 can be incident on the positioning light detector 72 through the positioning hole 41f of the cassette carrying turntable 41. The ON/OFF signal of the third light source 71 received by the positioning photodetector 72 when the cassette 10 is rotated is used as a function of the rotation positioning of the cassette 10.

Referring again to FIG. 1 , the light source detecting system 50 includes a first light source 51 , a second light source 52 , a first light detector 53 , a second light detector 54 , and a third light detector . 55, wherein the first light source 51 serves as an absorption light source to provide energy absorption of the direct incident light source required for the sample, and is located above the cassette carrying unit 40, and the set position corresponds to the first opening 41b (refer to FIG. 5) The first light source 51 may be a light emitting diode, but is not limited thereto, and may be another light source that can provide light absorption of the sample; the light beam B1 from the first light source 51 is as shown in FIG. Generally, the sample is vertically penetrated through the sample and incident on the first photodetector 53 via the first opening 41b.

The second light source 52 acts as a fluorescent excitation source on the side of the cassette carrying unit 40. The second light source 52 includes a semiconductor laser 52a and a focusing lens (FOCAL LENS) 52b disposed in front of the semiconductor laser 52a. The focusing lens 52b adjusts the laser beam output from the semiconductor laser 52a; in detail, the semiconductor The laser 52a can control the output power magnitude and stability of the laser beam via the controller 60, and since the beam of the semiconductor laser 52a is a radial output, the focusing lens 52b is added to adjust the laser beam to make the laser The beam energy can be more concentrated laterally incident on the sample in the cassette 10, allowing the sample to fully excite the fluorescent reaction.

In addition, it should be understood that the configuration of the second light source 52 is not limited thereto, and may be other light sources of different wavelengths that allow the sample to excite a fluorescent reaction.

Moreover, the laser beam B2 from the semiconductor laser 52a of the second light source 52 passes through the sample horizontally through the opening 41a, and is bent at an angle and incident on the second through the second opening 41c as shown in FIG. The photodetector 54; it should be understood that the predetermined angle may be 90 degrees, but is not limited thereto, as long as the light from the second light source 52 can be incident on the angle of the second photodetector 54.

The first photodetector 53 is disposed as an absorption light reaction unit under the cassette carrying unit 40, and the second photodetector 54 is used as a fluorescent detecting unit, and is also located below the cassette carrying unit 40. The light source detecting system 50 further includes an objective lens 56 and an optical filter 57 respectively disposed upstream of the incident light beam of the second photodetector 54, thereby changing the energy of the light source generated by the sample. Small and radially divergent, the diffracted light source can be collected through the objective lens 56, so that the second photodetector 54 can more accurately receive the change between the sample concentration and the light source energy; in addition, the optical filter 57 is mainly Among the light sources received by the objective lens 56, some unwanted stray light sources are filtered out to avoid affecting the measurement results.

The third photodetector 55 is disposed as a cold light detecting unit disposed below the cassette carrying unit 40 in a manner corresponding to the third opening 41d, and may be a photomultiplier tube module (PMT); The optical signal size detected by the photodetector 55 represents the change in the amount of luminescence energy produced by the sample.

As described above, since the motor driving unit 30 adopts a non-coaxial transmission design, the photodetectors 53, 54 and 55 can be disposed under the cassette carrying unit 40. In detail, the photodetector 53 can be disposed. 54 and 55 are disposed below the cassette carrying turntable 41 so as to overlap all or part of the cassette carrying turntable 41, whereby the miniaturization of the entire apparatus can be achieved.

Referring to FIG. 6, the controller 60 is electrically connected to the motor driving unit 30 and the light source detecting system 50 respectively, so that the cassette carrying unit 40 can be rotated by different rotation numbers via the motor driving unit 30, and the light source detecting system can be separately controlled. The light sources 51, 52 of the 50 actuate and receive signals from the photodetectors 53, 54, 55.

The basic configuration of the multi-source biochemical detecting device 1 of the present invention is as described above, and the multi-source biochemical detecting method of the present invention will be described below.

Referring to FIG. 7, the multi-source biochemical detection method of the present invention comprises the following steps: First, in step S11, the cassette 10 is placed on the cassette carrying unit 40; then, in step S12, the whole body of the human finger is taken ( About 60 μL) is added to the injection hole of the cassette 10 (not shown); then, in step S13, the motor drive unit 30 starts to bring the cassette carrying unit 40 into the high speed RPM rotation mode to perform plasma and blood cell separation in the cassette 10. The step of separating the plasma into a reaction with the reagent previously placed in the separation chamber of the cassette 10 to generate a reaction, and then entering the phase of the optical energy detection of the reactant, the motor driving unit 30 switches to the low-speed RPM rotation mode; Thereafter, in step S14, a sample which is incident on the separation chamber of the cassette 10 by a first light beam B1 and a second light beam B2 (refer to FIG. 5) is simultaneously generated (that is, the separated plasma and the reagent are mixed and produced). The first light beam B1 passing through the sample is detected by the first photodetector 53 disposed under the cassette carrying unit 40, and the fluorescent light generated by the second light beam B2 passing through the sample is set by Cartridge carrying unit 40 The second light detector 54 detects that the first light beam B1 is generated by the first light source 51, and vertically penetrates the sample from above the cassette carrying unit 40 and is incident on the first through the first opening 41b. The photodetector 53 is generated by the second light source 52, and is horizontally bent from the side of the cassette carrying unit 40 through the sample 41a through the opening 41a, bent at a predetermined angle, and incident through the second opening 41c. To the second photodetector 54, the first photodetector 53 measures the optical energy change generated after the sample absorbs the light source, and the second photodetector 54 measures the fluorescent optical signal excited by the sample. . The luminescence reaction detecting portion of the sample is measured by the third photodetector 55. The optical signal intensity changes detected by the first photodetector 53, the second photodetector 54, and the third photodetector 55 will correspond to the concentration of the sample, according to the ratio of the signal to the concentration. Then, through the system calculation circuit and data analysis, the biochemical immune analysis values to be measured can be estimated.

According to the multi-source biochemical detecting device and method of the present invention, two or more light sources can be measured at the same time, without the need of mechanism conversion, and can be replaced by the detection and lateral opening on the cassette carrying unit. The mirror of Zhiguang Road simplifies the optical components in the design of the optical path; in addition, the opening of the card 匣 carrying unit of the cassette carrying the bottom of the turntable further simplifies the optical components on the optical path, and the light source can be directly incident on the sample; In addition, the motor drive unit adopts a non-coaxial transmission design, and the photodetector can be disposed under the cassette carrying unit to achieve miniaturization of the entire device.

Although the present invention has been disclosed in the above preferred embodiments, it is not intended to limit the invention, and any one of ordinary skill in the art can make any changes without departing from the spirit and scope of the invention. The scope of protection of the present invention is therefore defined by the scope of the appended claims.

1. . . Multi-source biochemical detection device

10. . . Card

20. . . Ontology

twenty one. . . First base

twenty two. . . Second base

twenty three. . . Third base

30. . . Motor drive unit

31. . . Belt

32. . . Motor body

33. . . Belt wheel

40. . . Card carrier unit

41. . . Card carrier

41a. . . Opening

41b. . . First opening

41c. . . Second opening

41d. . . Third opening

41e. . . Fourth opening

41f. . . Positioning hole

42. . . Palin

50. . . Light source detection system

51. . . First light source

52. . . Second light source

52a. . . Semiconductor laser

52b. . . Focusing lens

53. . . First photodetector

54. . . Second photodetector

55. . . Third light detector

56. . . Objective lens

57. . . Optical filter

60. . . Controller

70. . . Positioning unit

71. . . Third light source

72. . . Positioning light detector

C. . . The center of the cassette carrying carousel

B1. . . First beam

B2. . . Second beam

1 is a schematic view of an embodiment of a multi-source biochemical detecting device according to the present invention;

2a, 2b are diagrams of the cassette carrying unit in Fig. 1;

Figure 3 is a schematic view of the cassette carrying turntable in Figure 2a;

Figure 4 is a schematic view showing an embodiment of a positioning unit in the multi-source biochemical detecting device of the present invention;

Figure 5 is a schematic diagram of an optical path of an embodiment of a light source detecting system in the multi-source biochemical detecting device of the present invention;

Figure 6 is a block diagram of a multi-source biochemical detection device of the present invention, wherein an embodiment of the circuit;

Figure 7 is a flow chart of one embodiment of the multi-source biochemical detection method of the present invention.

1. . . Multi-source biochemical detection device

10. . . Card

20. . . Ontology

twenty one. . . First base

twenty two. . . Second base

twenty three. . . Third base

30. . . Motor drive unit

31. . . Belt

32. . . Motor body

33. . . Belt wheel

40. . . Card carrier unit

51. . . First light source

52. . . Second light source

52a. . . Semiconductor laser

52b. . . Focusing lens

53. . . First photodetector

54. . . Second photodetector

55. . . Third light detector

56. . . Objective lens

57. . . Optical filter

72. . . Positioning light detector

Claims (26)

A multi-light source biochemical detecting device for analyzing a sample contained in a cassette, comprising: a motor driving unit; a cassette carrying unit carrying the cassette and having an opening and a first opening And a second opening, wherein the motor driving unit drives the card bearing unit to rotate; a light source detecting system includes a first light source, a second light source, a first light detector, and a second a light detector, wherein a light beam from the first light source penetrates the sample in a straight line and is incident on the first photodetector via the first opening, and a light beam from the second light source passes through the opening After the sample is bent at an angle, it is incident on the second photodetector via the second opening. The multi-light source biochemical detection device of claim 1, wherein the first photodetector and the second photodetector are located below the cassette carrying unit. The multi-light source biochemical detecting device according to claim 1, wherein the first opening and the second opening are formed at a bottom of the cassette carrying unit. The multi-light source biochemical detecting device according to claim 1, wherein the first light source is located above the cassette carrying unit, and the second light source is located at a side of the cassette carrying unit. The multi-light source biochemical detecting device according to claim 1, wherein the position of the first light source corresponds to the first opening. Multi-source biochemical test equipment as described in item 1 of the patent application scope The opening is formed on a side of the cassette carrying unit. The multi-light source biochemical detecting device according to the first aspect of the invention, wherein the card bearing unit further has a third opening, and the multi-light source biochemical detecting device further comprises a third photodetector, The third opening is arranged in a corresponding manner. The multi-light source biochemical detecting device according to claim 7, wherein the third photodetector is located below the cassette carrying unit. The multi-light source biochemical detecting device according to claim 7, wherein the third photodetector is a photomultiplier tube module. The multi-light source biochemical detection device of claim 7, wherein the first opening is connected to the center of the cassette carrying unit, and the connection between the second opening and the center of the cassette carrying unit is The angle between them is 90 degrees. The multi-light source biochemical detecting device according to claim 7, wherein the opening is plural, and the positions of the openings correspond to the first opening, the second opening, and the third opening, respectively. . The multi-light source biochemical detecting device of claim 1, wherein the light source detecting system further comprises an objective lens and an optical filter respectively disposed upstream of the incident light beam of the second photodetector. The multi-light source biochemical detecting device according to claim 1, wherein the angle is 90 degrees. The multi-light source biochemical detecting device according to claim 1, wherein the motor driving unit comprises: a belt coupled with the cassette carrying unit; A motor body is coupled to the belt to drive the cassette carrying unit to rotate by the belt. The multi-light source biochemical detecting device according to claim 1, wherein the motor driving unit and the cassette carrying unit are coupled in a non-coaxial manner. The multi-light source biochemical detecting device according to claim 1, wherein the second light source is a semiconductor laser. The multi-light source biochemical detecting device of claim 16, wherein the light source detecting system further comprises a focusing lens disposed before the semiconductor laser to adjust a laser beam output from the semiconductor laser. The multi-light source biochemical detecting device according to claim 1, wherein the first light source is a light emitting diode. The multi-light source biochemical detecting device according to claim 1, wherein the cassette carrying unit further has a positioning hole. The multi-light source biochemical detecting device according to claim 19, further comprising a third light source and a positioning photodetector, wherein the light beam from the third light source is incident on the positioning through the positioning hole The photodetector is rotated and positioned as the cassette carrying unit. The multi-light source biochemical detecting device according to claim 1, further comprising a controller electrically connected to the motor driving unit and the light source detecting system. A multi-source biochemical detection method for analyzing a sample contained in a cassette, comprising: placing the cassette on a cassette carrying unit, wherein the cassette carrying sheet The element has an opening, a first opening, and a second opening; rotating the cassette carrying unit; simultaneously injecting a first beam and a second beam into the sample, and passing the first beam of the sample The first photodetector disposed under the cassette carrying unit is detected, and the fluorescent light generated by the second beam passing through the sample is a second photodetector disposed under the cassette carrying unit. Detecting, wherein the first light beam penetrates the sample in a straight line and is incident on the first photodetector via the first opening, and the second light beam is bent at an angle after passing the sample through the opening And entering the second photodetector via the second opening. The multi-light source biochemical detection method according to claim 22, wherein the cassette carrying unit can rotate with different rotation numbers. The multi-source biochemical detection method according to claim 22, wherein the first beam is incident from the top of the cassette carrying unit to the sample, and the second beam is incident from a side of the cassette carrying unit. To the sample. The multi-source biochemical detection method according to claim 22, wherein the cold light of the sample is detected by a third photodetector disposed under the cassette carrying unit. The multi-source biochemical detection method as described in claim 22, wherein the angle is 90 degrees.