Abstract:
The invention is directed to a sieving apparatus for a bio-chip, which has a light source, a HOE unit, a splitter, an objective lens, a filter, and an optical signal sensor. The HOE unit is coupled with a light source, so as to diffract the light into a zeroth order beam and a first order beam. The zeroth order beam has no deflection but the first order beam has a deflection from the zeroth order beam. The splitter is coupled to the HOE unit, so as to lead the two beams to the objective lens, which further leads the two beams to the bio-chip, in which the first order beam is incident onto the bio-chip from an incident angle, causing a florescent light from the sample. The bio-chip also reflects the zeroth order beam. Both the reflected zeroth order beam and the fluorescent light travel through the objective lens and the splitter. The filter is coupled to the splitter, so that an undesired portion of the light beams incident on the splitter is filtered. The optical sensor receives the light beams after the filter. The zeroth order beam is used to generate a focusing signal and a tracking signal. The focussing signal and the tracking signal are used to control the servo, so as to align the optical sensor to the samples for detecting the florescent light. Alternatively, the sensor can be fixed but the bio-chip is shifted by the servo system.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application claims the priority benefit of Taiwan application Ser. No. 89105441, filed Mar. 24, 2000. 
     BACKGROUND OF THE INVENTION 
     1. Field of Invention 
     The present invention relates to an optical inspection system. More particularly, the present invention relates to a sieving apparatus for sample on a bio-chip. 
     2. Description of Related Art 
     A bio-chip is widely used in a biologic inspection system to sieve out the interesting samples. Usually, one sample or various samples arc put on a bio-chip at the detection units, respectively. The detection units on the bio-chip are sieved one by one. The bio-chip is implemented into a detection system for sieving each sample. The detection system is an optical detection system. The sample is illuminated by a light beam generated from a light source. The optical detection system then detects a fluorescent light from the sample on the bio-chip, whereby a particular component content in the sample is detected. As a result, the samples having the particular component are sieved out from the samples pool. 
     The bio-chip typically includes a specified material at the detection units. Once the samples are put onto the bio-chip, the material reacts with the particular component contained if the detected sample contain the particular component. After reaction, the component becomes fluorescent if the reacted component is illuminated by a light with a specific wavelength. Currently, the bio-chip detection apparatus needs an external light source. The external light source emits a light beam that is incident onto the detection unit of the bio-chip from side. If the fluorescent signal is successfully detected out, the sample is indicated as the sample containing the particular component. 
     FIG. 1 is a drawing, schematically illustrating a conventional optical detection system for a bio-chip. In FIG. 1, the conventional optical detection system includes an objective lens  100 , a slit  102 , a filter  104 , a photomultiplier tube  106 , an electronic filter  108 , and a computer  110 . 
     A bio-chip  130  with the sample is illuminated by an argon ion laser beam  150  from side with an incident angle of 45 degrees through a lens  140 . The laser beam illuminated the specified sample of the bio-chip  130 , then the sample containing the component produces a fluorescent light  120 . The fluorescent light  120  goes through the objective lens  100 , the slit  102 , the filter  104 , and then reach the photomultiplier tube  106 . The photomultiplier tube  106  amplifies the fluorescent light  120  and convert it into an electronic signal. The electronic signal is exported to the electronic filter  108 , and then to the computer  110  for processing. 
     In the foregoing conventional optical detection system for the bio-chip have to associate with an external light source. The whole system is complex and has a large volume. It is difficult to align and adjust. In this manner, the detection system for bio-chip is installed on a fixed frame only at a medical center or the similar centers. The sample sieving process is always performed at the centers. This causes very inconvenient and inefficient particularly when a large amount of samples need to be sieved. 
     SUMMARY OF THE INVENTION 
     The invention provides a sieving apparatus for a bio-chip. The sieving apparatus integrates the light source and the detecting part in a single apparatus. Since the sieving apparatus is well compacted, the sieving apparatus is portable and can efficiently process sieve for a large amount of samples. The sieving apparatus of the invention includes a holographic optical element (HOE), which allows a light beam to illuminate the sample of the bio-chip from side with a specific incident angle. The bio-chip can efficiently absorb the illuminating light and generate more fluorescent effect. The sieving efficiency is effectively improved. This is particularly helpful for processing a large amount of samples. Furthermore, the sieving apparatus can be easily aligned and adjusted for detecting the fluorescent signals. Further still, the reflection light from the bio-chip is used to automatically locate the detection point at the samples through a servo system. The sieving efficiency is further greatly improved. As a result, a large amount of samples can be efficiently sieved. 
     As embodied and broadly described herein, the invention provides a sieving apparatus for a bio-chip, which includes a light source, a HOE unit, a splitter, an objective lens, a filter, and an optical signal sensor. The HOE unit is coupled with a light source, so as to diffract the light into a zeroth order beam and a first order beam. The zeroth order beam has no deflection but the first order beam has a deflection from the zeroth order beam. The splitter is also coupled to the HOE unit, so as to lead the zeroth order beam and the first order beam to the objective lens. The objective lens further leads the two light beams to the bio-chip, in which the first order beam is incident onto the bio-chip from a specific incident angle, causing a florescent light from the sample. The bio-chip also reflects the zeroth order beam. Both the reflected zeroth order beam and the fluorescent light travel through the objective lens and the splitter. The filter is coupled to the splitter, so that the undesired portion of the light beams incident on the splitter is filtered by the filter. The optical sensor receives the light beams after the filter. The zeroth order beam is used to generate a focusing signal and a tracking signal. The focussing signal and the tracking signal are used to control the servo, so as to align the optical sensor to the samples for detecting the florescent light. The samples therefore are sieved to see whether the sample contains a particular component or not. 
     The invention provides another sieving apparatus for a bio-chip, which includes a light source, an HOE unit, a first splitter, a second splitter, an objective lens, a filter, a servo signal generating system, and a signal sensor. The HOE unit is coupled with a light source, so as to diffract the light source into a zeroth order beam and a first order beam. The zeroth order beam has no deflection, but the first order beam has a deflection from the zeroth order beam. The first splitter is coupled to the HOE unit, so as to lead the zeroth order beam and the first order beam to the objective lens. The two light beams then is led to the bio-chip through the objective lens. The first order beam is refracted by the objective lens, so that the first order beam is incident onto the sample of the bio-chip by a specific incident angle. If the sample contains the particular component, a fluorescent light is emitted from the sample. The bio-chip also reflects the zeroth order beam, which together with the fluorescent light travel back through the objective lens and reach the first splitter. The second splitter, which is coupled to the first splitter, then splits the two beams. A portion of the beams after the second splitter is led to the servo signal generating system, which is coupled to second splitter. The servo signal generating system accordingly generates a focusing signal and a tracking signal, which are used to control a shift of the bio-chip to a desired location. The beams passes through the second splitter is further filtered by the filter, and then is sensed by a signal sensor, so as to detecting the florescent light. The fluorescent light is generated by the sample contain the particular component. In this manner, the samples are sieved. 
     It is to be understood that both the foregoing general description and the following detailed description are exemplary, and are intended to provide further explanation of the invention as claimed. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification. The drawings illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention. In the drawings, 
     FIG. 1 is a drawing, schematically illustrating a conventional optical detection system for a bio-chip; 
     FIG. 2A is a drawing, schematically illustrating an optical detection system for bio-chip, according to the first preferred embodiment of the invention; 
     FIG. 2B is a drawing, schematically illustrating another optical detection system for bio-chip, according to the first preferred embodiment of the invention; 
     FIG. 3 is a drawing, schematically illustrating a circular HOE unit used in the optical detection system for bio-chip, according to the first preferred embodiment of the invention; and 
     FIG. 4 is a drawing, schematically illustrating an optical detection system for bio-chip, according to the second preferred embodiment of the invention. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Theory of the bio-chip for sieving samples is that the particular component of the sample has a chemical react with a material that is formed on a bio-chip at a detection unit. The detection unit can have one sample or various samples. The component after reaction absorbs light and becomes fluorescent when the component is illuminated by a light with a specific wavelength. For example, when a green light, such as a green laser light, with a wavelength of about 532 nm is incident onto the reacted component, a fluorescent light with a wavelength of about 540 nm is emitted. A sieving apparatus of bio-chip can detect the fluorescent light with the specific wavelength, so as to sieve the sample. Generally, the operation mechanism is similar to the operation mechanism used in an optical disc for accessing data. 
     First Embodiment 
     FIG. 2A is a drawing, schematically illustrating an optical detection system for bio-chip, according to the first preferred embodiment of the invention. In FIG. 2A, an optical sieving apparatus  200   a  is also an optical detection system. The optical detection system includes a light source  202   a,  an HOE unit  204   a,  a beam splitter  206   a,  an objective lens  208   a,  a filter  210   a,  and a signal sensor  212   a.  A bio-chip  230   a  is held by a holder  214   a.  Location of the holder  214   a  can be adjusted by a mechanical unit (not shown), such as a servo system. A cover glass  216   a  covers the bio-chip  230   a  for protection from contamination. The cover glass, for example, is about 0.1-1.2 mm. 
     In the sieving apparatus  200   a,  the light source  202   a,  such as a laser light source, is used to produce light to illuminate the bio-chip  230   a.  Wavelength of the light source can be about 400 nm-600 nm. The HOE unit  204   a  is coupled to the light source  202   a  for receiving the light beam  220   a  from the light source  202   a.  The HOE unit  204   a  then diffracts the light beam  220   a  to form a zeroth order beam  222   a  and a first order beam  224   a.  Due to the optical properties, the zeroth order beam has no deflection and travels on the optical path, but the first order beam has a deflection from the zeroth order beam. This phenomenon is a natural physical property for the HOE unit  204   a.    
     The beam splitter  206   a  is coupled to the HOE unit  204   a  for receiving the zeroth order beams  222   a  and the first order beam  224   a.  Generally, the HOE unit  204   a  is located between the light source  202   a  and the beam splitter  206   a.  The zeroth order beam  222   a  and the first order beam  224   a  are deflected by the beam splitter  206   a  onto the bio-chip at the detection unit that has the sample to be sieved. Between the beam splitter  206   a  and the bio-chip  230   a , the objective lens  208   a  is used to focus the zeroth order beam  222   a  and the first order beam  224   a  onto the desired sample on the bio-chip  230   a.  Due to the geometric design of the objective lens  208   a,  the first order beam is incident onto the sample by a specific incident angle  218   a  from side. The bio-chip  230   a  is properly shifted by the servo system, so as to scan all the samples for sieve. In this manner, the sample illuminated by the light from side has a better fluorescent efficiency. The incident angle  218   a  can range about 30-50 degrees. Preferably, the incident angle  218   a  is about 45 degrees. The numerical aperture (NA) of the objective lens  208   a  is about 0.4-0.6. The structure of the objective lens  208   a  can be, for example, a spherical lens, a rod lens, or similar lens, in which the rod lens can produce an elliptic light spot and has greater advantages for scanning the samples. 
     The filter  210   a  and the signal sensor  212   a  are located on the optical path at one side of the beam splitter  206   a  opposite to the side having the objective lens  208   a  and the bio-chip  230   a.  The filter  210   a  is coupled between the signal sensor  212   a  and the beam splitter  206   a.  The filter  210   a  filters undesired light in wavelength and allows the fluorescent light to pass and reach the signal sensor  212   a  to determine whether there is the desired fluorescent light. The signal sensor  212   a  includes photodetector to detect the fluorescent light. 
     Still referring to FIG. 2A, the light beam  220   a  from the light source  202   a  is diffracted by the HOE unit  204   a  into the zeroth order beam  222   a  and the first order beam  224   a.  The beam splitter  206   a  leads the beams  222   a  and  224   a  onto the objective lens  208   a,  and then onto the bio-chip  230   a.  The zeroth order beam  222   a  does not deflect from the optical axis but the first order beam deflects from the optical axis, surrounding the zeroth order beam. The first order beam  224   a  is refracted by the objective lens  208   a  and therefore is incident on the sample of the bio-chip  230   a  by the incident angle  218   a.  If the sample contains the detected component, the fluorescent light  226   a  is produced. The fluorescent light  226   a  travels back to the signal sensor  212   a  through the objective lens  208   a,  the beam splitter  206   a,  and the filter  210   a.  The zeroth order beam is reflected to an optical signal sensor for generating a tracking signal and focusing signal, used to control the servo system to move the bio-chip  230   a.    
     The HOE unit  204   a  can be a circular HOE unit. FIG. 3 is a drawing, schematically illustrating a circular HOE unit used in the optical detection system for bio-chip, according to the first preferred embodiment of the invention. In FIG. 3, the circular HOE unit  300  has several circular strips  302 , which are concentric and are gradually wider toward the circular periphery, in which the pitches between the strips are also gradually wider. The density of the strips near to the center is higher than the density near to the edge. 
     Similarly, FIG. 2B is a drawing, schematically illustrating another optical detection system for bio-chip, according to the first preferred embodiment of the invention. In FIG. 2B, the sieving apparatus of bio-chip  200   b  is similar to the one in FIG. 2A but has a different arrangement of locations for the beam signal sensor and the light source. The bio-chip  200   b  includes a light source  202   b,  an HOE unit  204   b,  a beam splitter  206   b,  an objective lens  208   b,  a filter  210   b,  and a signal sensor  212   b.  A bio-chip  230   b  is held by a holder  214   b.  Location of the holder  214   b  can be adjusted by a mechanical unit (not shown), such as a servo system. A cover glass  216   b  covers the bio-chip  230   b  for protection from contamination. The cover glass, for example, is about 0.1-1.2 mm. 
     In the sieving apparatus  200   b,  the light source  202   b,  such as a laser light source, is used to produce light to illuminate the bio-chip  230   b.  Wavelength of the light source can be about 400 nm-600 nm. The HOE unit  204   b  is coupled to the light source  202   b  for receiving the light beam  220   b  from the light source  202   b.  The HOE unit  204   b  then diffracts the light beam  220   b  to form a zeroth order beam  222   b  and a first order beam  224   b.  Due to the optical properties, the zeroth order beam has no deflection and travels on the optical path, but the first order beam  224   b  has a deflection from the zeroth order beam  222   b.    
     The beam splitter  206   b  is coupled to the HOE unit  204   b  for receiving the zeroth order beams  222   b  and the first order beam  224   b.  The HOE unit  204   b  is located between the light source  202   b  and the beam splitter  206   b.  The zeroth order beam  222   b  and the first order beam  224   b  travel through the beam splitter  206   b,  and reach the bio-chip  230   b.  Between the beam splitter  206   b  and the bio-chip  230   b,  the objective lens  208   b  is used to focus the zeroth order beam  222   b  and the first order beam  224   b  onto the desired sample on the bio-chip  230   a.  Due to the geometric design of the objective lens  208   b,  the first order beam is incident onto the sample by a specific incident angle  218   b  from side. The bio-chip  230   b  is properly shifted by the servo system, so as to scan all the samples for sieve. In this manner, the sample illuminated by the light from side has a better fluorescent efficiency. The incident angle  218   b  can range about 30-50 degrees. Preferably, the incident angle  218   b  is about 45 degrees. The NA of the objective lens  208   b  is about 0.4-0.6. The structure of the objective lens  208   b  can be, for example, a spherical lens, a rod lens, or similar lens, in which the rod lens can produce an elliptic light spot and has greater advantages for scanning the samples. 
     Still referring to FIG. 2B, the filter  210   b  and the signal sensor  212   b  are located on an optical path vertical to the optical path between the light source  202   b  and the bio-chip  230   b.  The filter  210   b  is coupled between the signal sensor  212   b  and the beam splitter  206   b.  As the zeroth order beam  222   b  and the first order beam  224   b  travel through the beam splitter  206   b  and the objective lens  208   b,  and reach the bio-chip  230   b,  the sample is illuminated by the first order beam  224   b  from side at the incident angle  218   b.  The sample therefore produces a fluorescent light  226   b  if the sample contains the component to be detected. The fluorescent light  226   b  travels along the optical path back to the beam splitter  206   b  through the objective lens  208   b.  The beam splitter  206   b  deflects the fluorescent light  226   b  into the filter  210   b.    
     The filter  210   b  typically filters undesired light in wavelength about other than the fluorescent light. The fluorescent light  226   b  passes the filter  210   b  and reaches the signal sensor  212   b  to indicate the component contained in the sample. The signal sensor  212   a  includes photodetector to detect the fluorescent light. The zeroth order beam  222   b  may also be reflected by the bio-chip  230   b  to an optical signal sensor to generate a tracking signal and a focusing signal, used for control the servo system to move the bio-chip  230   b.    
     The HOE unit  204   b  can be a circular HOE unit as shown in FIG.  3 . The circular HOE unit  300  has several circular strips  302 , which are concentric and are gradually wider toward the circular periphery, in which the pitches between the strips are also gradually wider. The density of the strips near to the center is higher than the density near to the edge. 
     Second Embodiment 
     FIG. 4 is a drawing, schematically illustrating an optical detection system for bio-chip, according to a second preferred embodiment of the invention. In FIG. 4, a sieving apparatus for bio-chip  400  includes a light source  402 , an HOE unit  404 , a first beam splitter  406   a,  a second beam splitter  406   b,  an objective lens  408 , and filter  410 , a servo signal sensor  414 , and a signal sensor  412 . 
     Similar to the first embodiment, a bio-chip  430  is held by a holder  416 . Location of the holder  416  can be adjusted by a mechanical unit (not shown), such as a servo system. A cover glass  418  covers the bio-chip  430  for protection from contamination. The cover glass  418 , for example, is about 0.1-1.2 mm. 
     In FIG. 4, the light source  402 , such as a laser light source, is used to produce light to illuminate the bio-chip  430 . Wavelength of the light source can be about 400 nm-600 nm. The HOE unit  404  is coupled to the light source  402  for receiving the light beam  420  from the light source  402 . The HOE unit  204   a,  such as a circular HOE, then diffracts the light beam  420  to form a zeroth order beam  422  and a first order beam  424 . Due to the optical properties, the zeroth order beam  422  has no deflection and travels on the optical path, but the first order beam  424  has a deflection from the zeroth order beam  422 . 
     The first beam splitter  406   a  is coupled to the HOE unit  404  and is located on one side of the HOE unit  404  opposite to the light source  402 . The zeroth order beam  422  and the first order beam  424  are deflected by the first beam splitter  406   a.  The objective lens  408  is coupled to the first beam splitter  406   a,  so as to receive the zeroth order beam  422  and the first order beam  424  from the first beam splitter  406   a.  The objective lens  408  focuses the zeroth order and the first order beams onto the sample at the bio-chip  430 . The objective lens  408  also refracts the first order beam  424 , whereby the first order beam  424  is incident on the sample by an incident angle  428  to generate the fluorescent ling  426 . The incident angle  428  can range from about 30 degrees to about 50 degrees, in which 45 degrees is preferred. The NA of the objective lens  408  is about 04-06. The structure of the objective lens  408  can be, for example, a spherical lens, a rod lens, or similar lens, in which the rod lens can produce an elliptic light spot and has greater advantages for scanning the samples. 
     In FIG. 4, the second beam splitter  406   b  is coupled to the first beam splitter  406   a  at the side opposite to the bio-chip  430 . The fluorescent light  426  together with the zeroth order beam  422  reflected by the bio-chip  430  travel along the optical path through the objective lens  408 , the first beam splitter  406   a,  and reach the second beam splitter  406   b.  A portion of the zeroth order beam  433  and the fluorescent light  426  is deflected by second beam splitter  406   b  onto the servo signal sensor  414 . The servo signal sensor  414  can generated the tracking signal and the focusing signal to control the servo system to move the bio-chip  430 . The rest portion of the zeroth order beam  422  and the fluorescent light  426  continuously travel through the filter  410  and reaches the signal sensor  412 . Since the filter  410  can filter away the light in wavelength about other than the wavelength of the fluorescent light  426 , only the fluorescent light  426  can reach the signal sensor  412 . The photodetector of the signal sensor  412  detects the fluorescent light to indicate whether the sample contain the component or not. 
     In the foregoing, the light beam  420  emitted from the light source  402  reaches the bio-chip  430  through the HOE unit  404 , the first beam splitter  406   a,  and the objective lens  408 . The HOE unit  404  diffracts the light beam  420  to be the zeroth order beam  422  and the first order beam  424 . The first beam splitter  406   a  deflects the beams onto the bio-chip  430  through the objective lens  408 . Since the effects from the HOE unit  404  and the objective lens  408 , the first order beam can be incident on the sample by the specific incident angle  428 , so as to illuminate the sample. If the sample contains the component, the fluorescent light is generated and is detected by the signal sensor  412 . A portion of the zeroth order beam is deflected by the second beam splitter  406   b  onto the servo signal sensor  414 , whereby the tracking signal and the focusing signal are generated for use to control the servo system. All samples on the bio-chip can be automatically and efficiently scaned. 
     Like the arrangement between FIG.  2 A and FIG. 2B, the light source  402  and the signal sensor  412  in FIG. 4 can be rearranged at the different optical path. 
     In conclusion, the sieving apparatus for bio-chip of the present invention integrates the light source and the sensing part into one single body. The system is greatly simplified, and the volume is also greatly reduced. This allows the sieving apparatus to be portable. In order to integrate the light source and the sensing part, an operation mechanism associate the HOE unit like the operation mechanism for optical pickup head is employed. As a result, the detection light spot can be automatically aligned to the samples. The samples on the bio-chip can be efficiently scanned and sieved. 
     It will be apparent to those skilled in the art that various modifications and variations can be made to the structure of the present invention without departing from the scope or spirit of the invention. In view of the foregoing, it is intended that the present invention cover modifications and variations of this invention provided they fall within the scope of the following claims and their equivalents.