Abstract:
Provided are an optical detection apparatus which can measure multi-channel samples at high speed and various wavelengths using an optical detector and a multi-channel sample analyzer employing the same. The optical detection apparatus includes an optical detector; a filter wheel having at least two color filters connected to each other in the shape of a disk; a plurality of optical channels through which a plurality of beams of light enter the filter wheel; and a mirror unit including a plurality of mirrors for sequentially reflecting the plurality of beams of light transmitted through the filter wheel to the optical detector, wherein the mirror unit rotates together with the filter wheel.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     This application claims the benefit of Korean Patent Application No. 10-2004-0071224, filed on Sep. 7, 2004, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference.  
         [0002]     1. Field of the Invention  
         [0003]     The present invention relates to an optical detection apparatus for multi-channel multi-color measurement and a multi-channel sample analyzer employing the same, and more particularly, to an optical detection apparatus which can measure multi-channel samples at high speed and various wavelengths using an optical detector and a multi-channel sample analyzer employing the same.  
         [0004]     2. Description of the Related Art  
         [0005]     A method of analyzing components of a sample which includes irradiating a specific wavelength of light onto the sample and then detecting a spectrum of light which is emitted from the sample is well known. For example, the respective bases of DNA can be labeled with fluorescent dyes having different emission wavelengths, and then the intensity light emitted from the fluorescent dyes is analyzed, thereby identifying the base sequence of the DNA.  
         [0006]      FIG. 1  is a schematic diagram of a conventional fluorescent analyzer  100 . Referring to  FIG. 1 , the conventional fluorescent analyzer  100  includes an optical unit  110  for irradiating light onto a sample  130  and a detection unit  120  for detecting light emitted from the sample  130 . The optical unit  110  generally includes a light source  112 , a dichroic mirror  114 , an objective lens  115 , and a sample holder  117 . The detection unit  120  includes an optical detector  125 , for example, a photo mutiplier tube (PMT), and a filter  121  which transmits a specific wavelength of light, etc. The light source  112  may include various sources, such as a halogen lamp, a light-emitting diode (LED), a laser, etc. Light emitted from the light source  112  is reflected by the dichroic mirror  114  and is partially absorbed by the sample  130  on the sample holder  117 . The light emitted from the sample  130  is transmitted through the dichroic mirror  114  and enters the detection unit  120 . The light which enters the detection unit  120  is transmitted through the filter  121 , thus having a specific wavelength and the optical detector  125  detects the intensity of light having the specific wavelength. By analyzing the intensity of the fluorescence light emitted from the sample by varying the wavelength property of the filter  121  or the light source  110 , the analyte of the sample can be identified.  
         [0007]     Recently, to increase the efficiency of analyzing a sample and determine the identity of the sample at high speed, a multi-channel sample analyzer, which can analyze a plurality of samples at once, has been developed. Multi-channel sample analysers can be roughly classified into apparatuses which determine a plurality of samples simultaneously using a plurality of optical detectors and apparatuses which determine a plurality of samples sequentially using an optical detector.  
         [0008]     Examples of the apparatuses which determine a plurality of samples simultaneously using a plurality of optical detectors include one which uses a number of separate optical detectors equal to the number of the samples, and the optical detectors detect the light emitted from the respective samples (for example, Cepheid Smart Cycler R ) and one in which a large area of light is irradiated to a plurality of samples at a time and a CCD having a large area detects the lights emitted from the samples (for example, ABI Prism 7000 R  and BioRad iCycler R ). However, when the number of separate optical detectors is equal to the number of the samples, filters which can cover a band of wavelength to be examined are disposed in front of the respective optical detectors. Thus, too many optical detectors and filters are used relative to the number of samples. On the other hand, when the CCD is used, only one filter wheel may be used. However, a CCD having a large area and a high accuracy required for fluorescent analysis is very expensive, thus increasing the production costs of the multi-channel sample analyzer and being unsuitable for small analyzers. Referring to  FIG. 2 , a rotating filter wheel is generally disposed in front of the CCD to perform multi-channel analysis using a variety of wavelengths. However, since a frame rate (the number of images which a CCD reads per second), which is related to a resolution of the CCD measurement, is limited, an increase in speed of the filter wheel is limited. Thus, there is still a limit when measuring many wavelengths at high speed.  
         [0009]     In an apparatus for determining a plurality of samples sequentially using an optical detector, generally, a plurality of samples are placed on a sample holder and the samples are measured by scanning. As described above, to perform the spectroscopic analysis of a sample at many wavelengths, the filter wheel should be rotated. Thus, a total measuring time calculated by multiplying a scanning time of the sample by a rotation time of the filter wheel can be increased.  
         [0010]     Thus, there is a need for a detection unit which can detect a plurality of samples at high speed and various wavelengths using an optical detector and a filter wheel.  
       SUMMARY OF THE INVENTION  
       [0011]     The present invention provides an optical detection apparatus which can measure multi-channel samples at high speed and various wavelengths using an optical detector and a multi-channel sample analyzer employing the same.  
         [0012]     The present invention also provides an optical detection apparatus for multi-channel multi-color measurement, which can have a small size and low production costs, and a multi-channel sample analyzer employing the same.  
         [0013]     According to an aspect of the present invention, there is provided an optical detection apparatus for multi-channel multi-color measurement comprising: an optical detector; a filter wheel having at least two color filters connected to each other in the shape of a disk; a plurality of optical channels through which a plurality of beams of light enter the filter wheel; and a mirror unit including a plurality of mirrors for sequentially reflecting the plurality of beams of light transmitted through the filter wheel to the optical detector, wherein the mirror unit rotates together with the filter wheel.  
         [0014]     The optical channels may be arranged in a row above the filter wheel along the radius direction of the filter wheel on a line connecting the center of the filter wheel to the optical detector. The optical channels farther from the optical detector may be shorter than the optical channels closer to the optical detector.  
         [0015]     Each of the mirrors of the mirror unit may correspond to one of the optical channels such that the beams of light exiting the optical channels are reflected to the optical detector and the mirrors may be disposed at the same radial positions as the corresponding optical channels. The mirrors in the mirror unit may be disposed at different azimuthal angles from one another on the mirror unit such that the beams of light exiting the optical channels are sequentially reflected to the optical detector during the rotation of the mirror unit.  
         [0016]     According to another aspect of the present invention, there is provided a multi-channel sample analyzer comprising: a light source unit for irradiating light onto each of a plurality of samples; an optical detection unit for detecting light beams emitted from the plurality of samples; and an optical transport unit for receiving the light beams emitted from the plurality of samples and transporting them to the optical detection unit, wherein the optical detection unit comprises an optical detector; a filter wheel having at least two color filters connected to each other in the shape of a disk; a plurality of optical channels through which a plurality of beams of light transported from the optical transport unit enter the filter wheel; and a mirror unit including a plurality of mirrors for sequentially reflecting each of the plurality of beams of light transmitted through the filter wheel to the optical detector, wherein the mirror unit rotates together with the filter wheel.  
         [0017]     The optical transport unit may comprise a light receiver for receiving the beams of light emitted from the samples and an optical fiber for transporting the beams of light from the light receiver to the optical detection unit.  
         [0018]     The multi-channel sample analyzer may further comprise a dichroic mirror for letting the light emitted from the light source unit proceed to the samples and letting the beams of light emitted from the samples proceed to the optical transport unit; a sample holder for holding the samples; and a driving unit for rotating the filter wheel and the mirror unit. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0019]     The above and other features and advantages of the present invention will become more apparent by describing in detail exemplary embodiments thereof with reference to the attached drawings in which:  
         [0020]      FIG. 1  is a schematic diagram of a conventional apparatus for fluorescence analysis;  
         [0021]      FIG. 2  is a schematic diagram of a conventional optical detection apparatus for multi-color measurement using a filter wheel;  
         [0022]      FIG. 3  is a schematic perspective view of an optical detection apparatus according to an embodiment of the present invention;  
         [0023]      FIG. 4  is a schematic cross-sectional view of the optical detection apparatus illustrated in  FIG. 3 ;  
         [0024]      FIG. 5  is a schematic diagram illustrating a principle of the optical detection apparatus according to an embodiment of the present invention;  
         [0025]      FIG. 6  is a schematic top plan view of the optical detection apparatus illustrated in  FIG. 3 ; and  
         [0026]      FIG. 7  is a schematic diagram of a multi-channel sample analyzer employing the optical detection apparatus illustrated in  FIG. 3  according to an embodiment of the present invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0027]     Hereinafter, the constitution and operation of an optical detection apparatus for multi-channel multi-color measurement according to an embodiment of the present invention and a multi-channel sample analyzer employing the same will be described in more detail with reference to the attached drawings.  
         [0028]      FIG. 3  is a schematic perspective view of an optical detection apparatus  10  according to an embodiment of the present invention. Referring to  FIG. 3 , the optical detection apparatus  10  comprises an optical detector  18 , for example, a photo multiplier tube (PMT), a filter wheel  12  having first through fourth color filters  12   a  through  12   d  connected to each other to form a disk form, a plurality of optical channels  17  and  19  through which a plurality of wavelengths of light enter the filter wheel  12 , and a mirror unit  20  having a plurality of mirrors  21  through  25  that sequentially reflect the wavelengths of light transmitted through the filter wheel  12  to the optical detector  18 . The optical detection apparatus  10  may further comprise, for example, a spindle motor  15  for rotating the filter wheel  12  and the mirror unit  20  at the same speed. The optical channels  17   a  through  17   d  let the light emitted from samples enter the filter wheel  12  and the optical channel  19  lets mark light for indicating one cycle of rotation of the filter wheel  12  enter the filter wheel  12 . Thus, the optical channel  19  may be a laser diode, for example. As illustrated in  FIG. 3 , the optical channels  17  and  19  are arranged in a row above the filter wheel  12  along a radial direction of the filter wheel  12  on a line connecting a rotational center of the filter wheel  12  to the optical detector  18 . Although  FIG. 3  illustrates the filter wheel  12  composed of the first through fourth color filters  12   a  through  12   d , this is shown for the purpose of illustration and the number of the color filters is not limited to four.  
         [0029]      FIG. 4  is a schematic cross-sectional view of the optical detection apparatus  10  illustrated in  FIG. 3 . Referring to  FIG. 4 , the optical detector  18  is near the circumference of the filter wheel  12  and the mirror unit  20 . The optical detector  18  detects the light reflected by the mirror unit  20 . In the mirror unit  20 , the plurality of mirrors  21  through  25  face the plurality of optical channels  17   a ,  17   b ,  17   c ,  17   d  and  19 , respectively, and reflect the light to the optical detector  18 .  
         [0030]     To ensure that the optical paths of the light exiting the plurality of optical channels  17  and  19  all have the same length, the lengths of the optical channels  17  and  19  become shorter for the optical channels  17  and  19  closer to the center of the filter wheel  12 . This is illustrated in  FIG. 5 . Referring to  FIG. 5 , to ensure that the optical detector  18  may accurately measure the strength of incident light, it is advantageous that the light enters uniformly through the detection surface of the optical detector  18 . To this end, the beams of light which enter the optical channels  17  and  19  must all be focused. In addition, to ensure that the beams of light which exit the optical channels  17  and  19  are all focused onto the detection surface of the optical detector  18  in the same manner, the lengths of the respective optical paths between the optical detector  18  and the optical channels  17  and  19  must be equal. Thus, the optical channel  17   a  facing the mirror  21  which is closest to the optical detector  18  is longest among the optical channels  17  and  19 . That is, the optical path between the optical channel  17   a  and the mirror  21  is longest. In this way, as illustrated in  FIG. 5 , the further the mirror is away from the optical detector  18 , the shorter the length of the corresponding optical channel. Lenses for focusing the light may be installed in respective incident portions of the optical channels  17 .  
         [0031]     If the plurality of mirrors  21  through  25  in the mirror unit  20  are arranged in a row along a radial direction of the filter wheel  12  like the optical channels  17  and  19 , the light reflected by a mirror disposed close to the center of the mirror unit  20  may be blocked by a mirror near the circumference of the mirror unit  20 . Also, if the mirrors  21  through  25  are formed of a semitransparent material, the beams of light exiting the plurality of optical channels  17  and  19  simultaneously enter the optical detector  18 , and thus, the optical detector  18  cannot accurately measure the beams of light.  FIG. 6  is a schematic top plan view illustrating the arrangement of the plurality of mirrors  21  through  25  in the optical detection apparatus  10  illustrated in  FIG. 3 . Such arrangement can overcome the above problems. Referring to  FIG. 6 , “X” designates the positions of the plurality of mirrors  21  through  25  in the mirror unit  20  and “O” designates the positions of the optical channels  17  and  19 .  
         [0032]     Referring to  FIG. 6 , the mirrors  21  through  25  of the mirror unit  20  are separated from each other by a predetermined azimuthal angle and disposed closer to the center of the mirror unit  20  in a predetermined azimuthal angle direction. That is, the plurality of mirrors  21  through  25  have the same radial positions as the optical channels  17   a ,  17   b ,  17   c ,  17   d  and  19 , respectively, but are arranged at different azimuthal angles from one another on the mirror unit  20 . Thus, when the mirror unit  20  rotates, the mirrors  21  through  25  may sequentially reflect the beams of light exiting the optical channels  17   a ,  17   b ,  17   c ,  17   d  and  19 , respectively, to the optical detector  18 .  
         [0033]     The mirrors  21  through  24 , which respectively correspond to the plurality of optical channels  17   a  through  17   d , through which the light exiting the samples enter the filter wheel  12 , are repeatedly installed in four regions of the mirror unit  20  which face the first through fourth color filters  12   a  through  12   d , respectively. For example, referring to  FIG. 6 , a first set of mirrors  21   a  through  24   a  which respectively correspond to the optical channels  17   a  through  17   d  are installed in the region corresponding to the first color filter  12   a , a second set of mirrors  21   b  through  24   b  which respectively correspond to the optical channels  17   a  through  17   d  are installed in the region corresponding to the second color filter  12   b , a third set of mirrors  21   c  through  24   c  which respectively correspond to the optical channels  17   a  through  17   d  are installed in the region corresponding to the third color filter  12   c , and a fourth set of mirrors  21   d  through  24   d  which respectively correspond to the optical channels  17   a  through  17   d  are installed in the region corresponding to the fourth color filter  12   d . That is, in the mirror unit  20 , the number of mirrors that correspond to each of the optical channels  17  is identical to the number of the first through fourth color filters  12   a  through  12   d  in the filter wheel  12 . Meanwhile, there is only one of the mirror  25  which corresponds to the optical channel  19  which emits the mark light for indicating one cycle of the filter wheel  12 .  
         [0034]     The operation of the optical detection apparatus  10  is as follows. First, the filter wheel  12  and the mirror unit  20  are rotated in a counter-clockwise direction by a driving unit, for example, a spindle motor  15 . The filter wheel  12  and the mirror unit  20  rotate at the same speed. Then, the light emitted from the samples enters the filter wheel  12  through the first through the fourth optical channels  17   a  through  17   d  and, simultaneously, the mark light for indicating one cycle of the filter wheel  12  enters the filter wheel  12  through the fifth optical channel  19 . When the filter wheel  12  and the mirror unit  20  rotate, the mark light from the fifth optical channel  19  is reflected by the mirror  25  and enters the optical detector  18 . The optical detector  18  receives the mark light and recognizes it as the start signal of a new channel. Then, the light from the fourth optical channel  17   d , which is transmitted through the first color filter  12   a , is reflected by the mirror  24   a  and enters the optical detector  18 . Subsequently, the light from the third optical channel  17   c , which is transmitted through the first color filter  12   a , is reflected by the mirror  23   a  and enters the optical detector  18 . Then, the beams of light from the second and the first optical channels  17   b  and  17   a , which have been transmitted through the first color filter  12   a , are sequentially reflected by the mirror  22   a  and the mirror  21   a , respectively. Although the optical channel  19 , which emits the mark light, is disposed closest to the center of the filter wheel  12  among the optical channels  17  and  19  in the present embodiment, the optical channels  17  and  19  may be disposed in different ways. Also, the filter wheel  12  and the mirror unit  20  may rotate in a clockwise direction.  
         [0035]     When the filter wheel  12  and the mirror unit  20  rotate continuously in the counter-clockwise direction, the light from the fourth optical channel  17   d , which is transmitted through the second color filter  12   b , is reflected by the mirror  24   b  and enters the optical detector  18 . Similarly, the beams of light from the third through the first optical channels  17   c  through  17   a , which are transmitted through the second color filter  12   b , are sequentially reflected by the mirrors  23   b  to  21   b , respectively, and enter the optical detector  18 . In this manner, the beams of light from the optical channels  17   d  through  17   a , which are transmitted through the third color filter  12   c , are sequentially reflected by the mirrors  24   c  through  21   c , respectively, and enter the optical detector  18 , and the beams of light from the optical channels  17   d  through  17   a , which are transmitted through the fourth color filter  12   d , are sequentially reflected by the mirrors  24   d  through  21   d , respectively, and enter the optical detector  18 .  
         [0036]     After the filter wheel  12  and the mirror unit  20  rotate once, the mark light from the fifth optical channel  19  is reflected by the mirror  25  and enters the optical detector  18   a  second time. Thus, the optical detector  18  receives the mark light and recognizes it as the start signal of a new channel. At the same time, the beams of light emitted from other samples enter the optical detector  18  through the optical channels  17   a  through  17   d . Then, the above process is repeated.  
         [0037]     As explained above, the optical detection apparatus  10  may measure light from a plurality of multi-channel samples at high speed and various wavelengths using only one optical detector  18 . In addition, the optical detection apparatus  10  has a simplified structure, and thus, can have a small size. The optical detection apparatus  10  illustrated in  FIG. 3 , for example, may be constructed with a radius of about 25 mm. Although only four optical channels  17   a  through  17   d  are used in the present embodiment, this example is given for the purpose of illustration and the number of the optical channels is not limited to four. When more optical channels are used, the number of mirrors in the mirror unit  20  must be increased accordingly.  
         [0038]      FIG. 7  is a schematic diagram of a multi-channel sample analyzer employing the optical detection apparatus  10  according to an embodiment of the present invention. Referring to  FIG. 7 , the multi-channel sample analyzer  30  according to an embodiment of the present invention comprises a light source unit  41  for irradiating light onto a plurality of samples  50 , an optical detection unit  10  for detecting light emitted from the plurality of samples  50 , and an optical transport unit  60  and  61  for receiving the light emitted from the plurality of samples  50  and transporting the light to the optical detection unit  10 . The multi-channel sample analyzer  30  may further comprise a sample holder  43  for holding the plurality of samples  50 .  
         [0039]     The light source unit  41  may have various structures, as described above regarding the conventional apparatus. For example, the light source unit  41  may have a plurality of light sources that separately irradiate light onto the plurality of samples  50 . Alternatively, the light source unit  41  may irradiate a large area of light onto the plurality of samples  50  at once and the samples  50  can be scanned at a high speed while rotating the samples  50  or the light. The samples  50  are stained, for example, with various fluorescent dyes that emit light of different wavelengths. When the light is irradiated onto the samples  50 , light beams having different wavelengths and intensities are emitted from the respective fluorescent materials. The emitted light beams are reflected by, for example, a dichroic mirror  42 , and received by a light receiver  60 . The light receiver  60  may be, for example, an optical fiber adaptor. The light beams received by the light receiver  60  are transported to the optical channels  17  through an optical fiber  61 . Then, as described above, while rotating the filter wheel  12  and the mirror unit  20 , the wavelengths and the intensities of the light beams emitted from the samples  50  are measured to analyze samples  50 .  
         [0040]     Although the multi-channel sample analyzer  30  is constructed such that the light beams emitted from the samples  50  are transported to the optical detection apparatus  10  via the light receiver  60  and the optical fiber  61  in  FIG. 7 , the multi-channel sample analyzer  30  may alternatively be constructed such that the light beams emitted from the samples  50  directly enter the optical channels  17 . In this case, the optical channels  17  may be, for example, a refractive lens only for focusing the light.  
         [0041]     A multi-channel fluorescence analyzer using the optical detection apparatus according to an embodiment of the present invention has been explained. However, the optical detection apparatus according to an embodiment of the present invention can be used as an optical detection unit for various types of multi-channel analyzers, as well as for the fluorescence analyzer.  
         [0042]     As describe above, in an optical detection apparatus according to the present invention, a plurality of optical signals with various wavelengths can be sequentially detected at high speed using an optical detector and a filter wheel. Also, the optical detection apparatus has a simplified structure, and thus, can have a small size and have low production costs.  
         [0043]     In addition, according to the present invention, the number of wavelengths which can be measured can be increased depending on the number of color filters in the wheel and the number of signals which can be detected can be controlled by varying the azimuthal angle between mirrors and the number of mirror sectors.  
         [0044]     While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art that various changes in form and details may be made therein without departing from the spirit and scope of the present invention as defined by the following claims.