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`(19) [Issuing Country] Japan Patent Office (JP)
`(12) [Publication Type] Gazette of Unexamined Patent Applications (A)
`(11) [Publication Number] 2001-242081 (P2001-242081A)
`(43) [Publication Date] September 7, 2001 (2001.9.7)
`
`(51) [Int.Cl.7]
`C01N 21/64
`C12M 1/00
`
`1/34
`C12N 11/14
`[FI]
`G01N 21/64 F
`
`
`Z
`C12M 1/00 A
`
`1/34 Z
`C12N 11/14
`[Theme Codes (Reference)]
`2G043
`2G045
`2G058
`2H087
`4B024
`[Examination Request] Not Yet Received
`[Number of Claims] 12
`[Application Format] Online (OL)
`
`[Total Number of Pages] 10
`
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`Continued on Last Page
`
`(21) [Application Number] 2000-52710 (P2000-52710)
`(22) [Filing Date] February 29, 2000 (2000.2.29)
`(71) [Applicant]
`[Identification Number] 000004112
`[Name] Nikon Corporation
`[Address] 3-2-3, Marunouchi, Chiyoda-ku, Tokyo
`(72) [Inventor]
`[Name] Yutaka IWASAKI
`[Address] Nikon Corporation, 3-2-3, Marunouchi, Chiyoda-ku, Tokyo
`(72) [Inventor]
`[Name] Yoshihiko SUZUKI
`[Address] Nikon Corporation, 3-2-3, Marunouchi, Chiyoda-ku, Tokyo
`Continued on Last Page
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`(54) [Title of the Invention]
`
`DNA Chip Reading Head and DNA Chip Reader
`
`(57) [Abstract]
`
`[Problem]
`
`To provide a DNA chip reading head of greatly reduced size and weight, and
`a more compact DNA chip reader incorporating this DNA chip reading head.
`
`[Solution]
`
`The DNA chip reader of the present invention comprises a semiconductor
`laser, an aspherical objective lens condensing fluorescence generated by a
`DNA chip, the DNA chip having been exposed to a laser beam from the
`semiconductor laser, an aspherical imaging lens directing the fluorescence
`passing through the aspherical objective lens to a light-receiving element, a
`dichroic mirror acting as a half mirror for the laser beam from the light
`source, directing the laser beam to the aspherical objective lens while
`directing the fluorescence passing through the lens to the aspherical imaging
`lens, and an aperture arranged between the aspherical imaging lens and the
`light-receiving element, each of these components being arranged inside a
`single case.
`
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`[Claims]
`
`[Claim 1]
`
`A DNA chip reading head comprising:
`a semiconductor laser light source;
`an objective lens for condensing fluorescence generated by a DNA chip, the
`DNA chip having been exposed to a laser beam from the semiconductor
`laser;
`an imaging lens directing the fluorescence passing through the aspherical
`objective lens to a light-receiving element;
`a dichroic mirror acting as a half mirror for the laser beam from the light
`source, directing the laser beam to the aspherical objective lens while
`directing the fluorescence passing through the lens to the aspherical imaging
`lens; and
`an aperture arranged between the aspherical imaging lens and the light-
`receiving element;
`each of these components being arranged inside a single case, and
`at least one of the objective lens and the imaging lens being an aspherical
`lens.
`
`[Claim 2]
`
`A DNA chip reading head according to claim 1 further comprising:
`a second dichroic mirror arranged between the dichroic mirror and the
`imaging lens for reflecting the laser beam and allowing fluorescence to pass;
`and
`an autofocus light-receiving element for receiving the laser beam reflected
`by the second dichroic mirror and detecting the focal point.
`
`[Claim 3]
`
`A DNA chip reading head comprising:
`a semiconductor laser light source arranged on one end of a substrate;
`a waveguide for directing the laser beam from the light source towards a
`grating coupler;
`the grating coupler exposing a DNA chip to the laser beam from the
`waveguide; and
`a light-receiving element for receiving fluorescence generated by the DNA
`chip;
`the waveguide, the grating coupler, and the light-receiving element being
`integrally mounted on the substrate.
`
`[Claim 4]
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`
`A DNA chip reading head according to claim 3 further comprising:
`a deflection condensing grating for defecting and condensing the laser beam
`reflected by the DNA chip; and
`an autofocus light-receiving element arranged facing the deflection
`condensing grating for receiving the reflected laser beam deflected and
`condensed by the deflection condensing grating;
`the deflection condensing grating and the autofocus light-receiving element
`being mounted on the substrate.
`
`[Claim 5]
`
`A DNA chip reading device comprising:
`a stage for fixing the DNA chip;
`a reading head for measuring the intensity of the fluorescence generated by
`the DNA chip exposed to a laser beam;
`a scanning device including the reading head for scanning the DNA chip; and
`a control device for outputting scanning signals to the scanning device,
`receiving signals corresponding to the intensity of the fluorescence from the
`head, and storing signals on the intensity of the fluorescence corresponding
`to the coordinates of the fluorescence.
`
`[Claim 6]
`
`A DNA chip reading device according to claim 5, wherein the reading head
`has an autofocusing mechanism.
`
`[Claim 7]
`
`A DNA chip reading device according to claim 5, wherein the reading head is
`a laser pickup head.
`
`[Claim 8]
`
`A DNA chip reading device according to claim 5, wherein the reading head
`has an optical waveguide device comprising a condensing element and a
`light-receiving element arranged on a substrate.
`
`[Claim 9]
`
`A DNA chip reading device according to claim 8, wherein the condensing
`element is a grating coupler, and a wavelength filter is arranged on the
`light-receiving element.
`
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`[Claim 10]
`
`A DNA chip reading device according to claim 8, wherein the optical
`waveguide device is an interdigital electrode for generating surface acoustic
`waves at a position perpendicular to the optical waveguide.
`
`[Claim 11]
`
`A DNA chip reading device according to claim 8, wherein the optical
`waveguide has a periodically poled structure.
`
`[Claim 12]
`
`A DNA chip reading device according to any of claims 8 through 11, wherein
`the reading head comprises a plurality of optical waveguide devices arranged
`on a single substrate.
`
`[Detailed Description of the Invention]
`
`[0001]
`
`[Technical Field of the Invention]
`
`The present invention relates to a DNA chip reading device for identifying
`the structure of genetic components using the complementary interaction
`between genetic components.
`
`[0002]
`
`[Prior Art]
`
`In recent years, the use of genomes has been extended to a wide variety of
`fields ranging from the identification of pathogens and the treatment of
`diseases in the medical field to the improvement of seeds by genetic
`recombination in the agricultural field. When genomes are used, the
`structure of the target organism has to be clarified on the genetic level.
`
`[0003]
`
`In order to identify the structure of the human on the genetic level, that is,
`the nucleotide sequence of a gene in the region of interest, DNA chips and
`chip reading devices have been developed and put to practical use. The
`nucleotide sequence of the human body is identified using these devices in
`the following manner.
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`
`[0004]
`
`First, a DNA chip is prepared with different types of DNA probes arranged at
`predetermined positions. These DNA probes are structures with the desired
`nucleotide or oligonucleotide sequence.
`
`[0005]
`
`A specimen is also prepared. In other words, DNA and RNA are extracted
`from the test object, and marked by binding a fluorescent substance.
`
`[0006]
`
`Next, a specimen is added to the DNA chip. The nucleotide sequence of each
`DNA probe is a sequence of four different bases (adenine: A, guanine: G,
`cytosine: C, thymine: T) in the desired order. These bases have
`complementary relationships, and adenine and thymine as well as cytosine
`and guanine are each bonded complementarily in a nucleotide. When a
`specimen is added to a DNA chip, partial double strands are created by
`hydrogen bonding of the bases in the specimen with the bases on the chip.
`The formation of double strands by hydrogen bonding is known as
`hybridization.
`
`[0007]
`
`For example, a DNA probe having an AGCTT nucleotide sequence selectively
`captures a specimen having a TCGAA nucleotide sequence. The specimen is
`marked in this way. As a result, the DNA probe that has captured the
`specimen generates fluorescence. This process generally occurs in liquid
`phase.
`
`[0008]
`
`After this process has occurred, the DNA chip is analyzed by a DNA reading
`device which measures the intensity and locations of fluorescence. In this
`way, the nucleotide sequences included in the specimen are identified.
`
`[0009]
`
`In a DNA chip, DNA problems having predetermined base sequences are
`immobilized at the appropriate intervals in spot-like fashion on a plate-like
`substrate. The diameter of each spot is from 20 to 200 μm, and several
`million DNA probes of the same type are immobilized in a single spot. The
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`length of the bases in an immobilized DNA probe is about twenty. These
`spots are formed in matrix-like fashion at intervals from 50 μm to 500 μm
`on a single DNA chip. The DNA probes immobilized at each spot have
`nucleotide sequences that are different from each other.
`
`[0010]
`
`The substrate of a DNA chip can be a glass substrate, Si substrate, or plastic
`substrate. The most commonly used substrate is slide glass for microscopes.
`Usually, the size is 75 mm x 25 mm and the thickness is 1 mm.
`
`[0011]
`
`Methods used to immobilize DNA probes on substrates include simultaneous
`synthesis and immobilization of the DNA probes in each layer of the
`substrate using photolithography, and synthesis of DNA probes separately
`using mechanical microspotting followed by immobilization on the substrate.
`Inkjet technology can be employed in both of these methods.
`
`[0012]
`
`The photolithographic technique uses photoreactive protective groups. These
`protective groups are used to protect the bonding of same or different base
`monomers. A novel base bonding reaction does not occur at the ends of the
`bases bonded by the protective group. These protective groups can be easily
`removed by exposure to light. A DNA chip is manufactured using the
`photolithographic technique in the following way.
`
`[0013]
`
`First, amino groups having a protective group are immobilized on the entire
`surface of the substrate. Next, spots for bonding specific bases are exposed
`to light using a method similar to the photolithographic technique commonly
`used in the semiconductor process. This affects only some bases exposed to
`light, and more bases can be introduced in subsequent bonding. Here, the
`desired bases having the same protective group on the end are bonded.
`
`[0014]
`
`Next, the shape of the photomask is changed and different spots are
`selectively exposed to light. Bases having protective groups are then bonded
`in the same manner. By repeating this process, the desired base sequences
`are obtained at each spot and the desired DNA chip is completed. For more
`details, see Science, no. 251, p. 767 (1991).
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`
`[0015]
`
`The inkjet technique used in DNA chip manufacturing jets tiny liquid droplets
`at particular spots on a two-dimensional plane using heat or the piezoelectric
`effect. The piezoelectric elements used here are combined with glass
`capillaries. By applying voltage to piezoelectric elements connected to liquid
`chambers, the change in the volume of the piezoelectric elements jets the
`liquid inside the chambers as liquid droplets from the capillaries connected to
`the chamber. The size of the jetted liquid droplets depends on the change in
`the volume of the piezoelectric elements and the physical properties of the
`liquid, but usually has an approximate diameter of 30 μm. This type of inkjet
`device can jet liquid droplets on a 10 KHz cycle.
`
`[0016]
`
`In the mechanical microspotting technique, a specimen containing DNA
`probes on the tip of a stainless steel pin is mechanically pressed against the
`substrate and immobilized. The spots obtained using this method range in
`size from 50 to 300 μm. After microspotting, post-treatments such as UV
`immobilization are performed.
`
`[0017]
`
`DNA chips to which a specimen has been added are analyzed using a DNA
`reading device known as an array reader. In an array reader, the DNA chip
`is exposed to light, the intensity of the fluorescence generated by the light is
`measured, and the intensity information and corresponding coordinates of
`each spot are displayed. An array reader includes a light source, optics, a
`reading head containing an integrated fluorescence intensity measuring
`sensor, a scanner for scanning the DNA chip, and a controller for outputting
`control signals and storing fluorescence intensity data along with the
`corresponding coordinates of the DNA probe.
`
`[0018]
`
`The intensity of the fluorescence generated is several orders of magnitude
`smaller than the intensity of the exposure light. Therefore, a dichroic mirror
`separates light by wavelength, and a beam splitter spatially separates the
`excitation light and fluorescent light. Because intensity calibration is
`unnecessary, the fluorescence intensity for two or more wavelengths is
`measured. A reading head is also inserted into these configurations.
`
`[0019]
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`
`There are two types of array readers. In one type, the fluorescence intensity
`of multiple spots is measured simultaneously using a CCD camera. In the
`other type, the DNA chip is scanned two-dimensionally using a confocal laser
`microscope.
`
`[0020]
`
`In an array reader using a CCD camera, a lamp is used as the light source
`for exposing the DNA chip, and the exposure can take place over a wide
`area. As a result, fluorescence can also be generated over a wide area and a
`1 cm2 area can be measured at the same time. Thus, the throughput is
`higher than that of an array reader using a confocal laser.
`
`[0021]
`
`An array reader using a confocal laser microscope uses a laser as the light
`source, and fluorescence is generated only where the DNA chip has been
`exposed to the focused laser spot. In a method using a confocal laser
`microscope, only an area 5 to 30 μm in diameter can be measured at the
`same time. Therefore, the throughput is lower than that of an array reader
`using a CCD. The scanning time is typically from 5 to 15 minutes when a 20
`x 60 mm area is scanned using a resolution of 10 μm.
`
`[0022]
`
`However, an array reader using a confocal laser microscope can eliminate
`optical noise and flares caused by contamination of the DNA chip in the
`depth direction using so-called confocal sectioning. The result is a higher
`signal-to-noise ratio than the CCD method.
`
`[0023]
`
`In both of these methods, the fluorescence intensity distribution of the
`measured DNA chip is outputted as two-dimensional image data having a
`strength resolution of about 16 bits. In order to easily identify an image, a
`pseudo-coloring process is sometimes required. A spot with strong
`fluorescence intensity in a detected image includes a DNA probe sequence
`and complementary nucleotide sequence from the specimen in the spot. In
`this way, a nucleotide sequence of the specimen can be identified from the
`magnitude of the fluorescence intensity in the spot.
`
`[0024]
`
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`
`[Problem Solved by the Invention]
`
`The DNA reading heads of the prior art described above are large and heavy.
`Also, in a DNA reading device using one of these heads, the reading head is
`arranged above the DNA chip. Therefore, durable support columns are
`required, and both the size and the cost of manufacturing the device
`increase.
`
`[0025]
`
`It is an object of the present invention to solve this problem by providing a
`DNA chip reading head and DNA chip reading device in which the size and
`weight can be significantly reduced.
`
`[0026]
`
`[Means of Solving the Problem]
`
`After conducting extensive research, the present inventors discovered that
`they could manufacture a compact, lightweight DNA chip reading head by
`improving the basic laser pickup head already used in optical disk devices.
`
`[0027]
`
`The invention in claim 1 is a DNA chip reading head comprising: a
`semiconductor laser light source; an objective lens for condensing
`fluorescence generated by a DNA chip, the DNA chip having been exposed to
`a laser beam from the semiconductor laser; an imaging lens directing the
`fluorescence passing through the aspherical objective lens to a light-
`receiving element; a dichroic mirror acting as a half mirror for the laser
`beam from the light source, directing the laser beam to the aspherical
`objective lens while directing the fluorescence passing through the lens to
`the aspherical imaging lens; and an aperture arranged between the
`aspherical imaging lens and the light-receiving element; each of these
`components being arranged inside a single case, and at least one of the
`objective lens and the imaging lens being an aspherical lens.
`
`[0028]
`
`When at least one of the objective lens and the imaging lens is an aspherical
`lens, the weight of the optics can be significantly reduced. This is a
`technology used in laser pickup heads. While not used in laser pickup heads,
`an aperture can be arranged between the imaging lens and the light-
`receiving element to block optical noise and improve the signal-to-noise
`
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`ratio. The intensity of the fluorescence is lower than the irradiated light. This
`configuration not only reduces the size and weight of the device, it also
`improves the signal-to-noise ratio. Because all of these small components
`are arranged inside a single case, the device mounted on the DNA chip
`reading device is small. The head can also perform X-Y scanning. In this
`way, the scanning of the DNA chip is more compact.
`
`[0029]
`
`The invention in claim 2 is a DNA chip reading head according to claim 1
`further comprising: a second dichroic mirror arranged between the dichroic
`mirror and the imaging lens for reflecting the laser beam and allowing
`fluorescence to pass; and an autofocus light-receiving element for receiving
`the laser beam reflected by the second dichroic mirror and detecting the
`focal point.
`
`[0030]
`
`When measuring the intensity of the fluorescence from the DNA chip at high
`speed, the irradiated light is preferably focused on the DNA chip. In this
`configuration, the head is not large so this can be done.
`
`[0031]
`
`The present inventors also discovered that the size and weight of a DNA chip
`reading head could also be significantly reduced by using waveguide
`elements recently adopted in optical communication.
`
`[0032]
`
`The invention in claim 3 is a DNA chip reading head comprising:
`a semiconductor laser light source arranged on one end of a substrate;
`a waveguide for directing the laser beam from the light source towards a
`grating coupler; the grating coupler exposing a DNA chip to the laser beam
`from the waveguide; and a light-receiving element for receiving fluorescence
`generated by the DNA chip; the waveguide, the grating coupler, and the
`light-receiving element being integrally mounted on the substrate. Because a
`waveguide element is used in this configuration, the DNA chip reading head
`can be reduced in size and weight to an extent similar to the invention in
`claim 1. Because the elements are integrally mounted on a single board, the
`device mounted on the DNA chip reading device is small.
`
`[0033]
`
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`The use of optical waveguide technology in a laser pickup for an optical disk
`has been proposed by Nishihara et al. (Laser Research, vol. 19, no. 4, 1991,
`pp. 344-353). However, the use of this technology in DNA chip reading
`heads has not been proposed.
`
`[0034]
`
`The invention in claim 4 is a DNA chip reading head according to claim 3
`further comprising: a deflection condensing grating for defecting and
`condensing the laser beam reflected by the DNA chip; and an autofocus
`light-receiving element arranged facing the deflection condensing grating for
`receiving the reflected laser beam deflected and condensed by the deflection
`condensing grating; the deflection condensing grating and the autofocus
`light-receiving element being mounted on the substrate.
`
`[0035]
`
`In this way, the element used to focus the laser beam on the DNA chip is
`integrally mounted on the same substrate. This reduces the size of the DNA
`chip reading head and facilitates high speed focusing.
`
`[0036]
`
`The present inventors discovered that scanning could be performed if the
`DNA chip reading head was small. For this reason, the overall device was
`made even smaller. The invention in claim 5 is a DNA chip reading device
`comprising: a stage for fixing the DNA chip; a reading head for measuring
`the intensity of the fluorescence generated by the DNA chip exposed to a
`laser beam; a scanning device including the reading head for scanning the
`DNA chip; and a control device for outputting scanning signals to the
`scanning device, receiving signals corresponding to the intensity of the
`fluorescence from the head, and storing signals on the intensity of the
`fluorescence corresponding to the coordinates of the fluorescence.
`
`[0037]
`
`While scanning a DNA chip, an area of the stage to be scanned and an area
`for the reading head to be fixed are required. In this configuration, the DNA
`reading device is small enough to cover nearly the same area as the stage
`on which the DNA chip has been fixed while the reading head is performing
`the scanning.
`
`[0038]
`
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`In claim 6, the reading head has an autofocusing mechanism. This facilitates
`high-speed measurement of a DNA chip.
`
`[0039]
`
`The invention in claim 7 is a DNA chip reading device according to claim 5,
`wherein the reading head is a laser pickup head. The invention in claim 8 is
`a DNA chip reading device according to claim 5, wherein the reading head
`has an optical waveguide device comprising a condensing element and a
`light-receiving element arranged on a substrate. These inventions are
`specific examples of compact, lightweight reading heads.
`
`[0040]
`
`The invention in claim 9 is a DNA chip reading device according to claim 8,
`wherein the condensing element is a grating coupler, and a wavelength filter
`is arranged on the light-receiving element.
`
`[0041]
`
`The wavelength filter only allows light of a predetermined wavelength to
`pass through. As a result, light other than the fluorescence is blocked by the
`filter and is not incident on the light-receiving element. This improves the
`signal-to-noise ratio. The grating coupler is a specific element of the
`condensing element used in an optical waveguide element.
`
`[0042]
`
`The invention in claim 10 is a DNA chip reading device according to claim 8,
`wherein the optical waveguide device is an interdigital electrode for
`generating surface acoustic waves at a position perpendicular to the optical
`waveguide.
`
`[0043]
`
`When a suitable substrate material is selected and a high frequency electric
`field is applied to the interdigital electrodes arranged on the substrate,
`surface acoustic waves are generated. The light traveling through the optical
`waveguide is then diffracted. Because of the high frequency, the diffraction
`angle is continuously changing. Therefore, in this configuration, light can be
`scanned on the X-axis or the Y-axis.
`
`[0044]
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`The invention in claim 11 is a DNA chip reading device according to claim 8,
`wherein the optical waveguide has a periodically poled structure.
`
`[0045]
`
`If a suitable substrate material is selected, a periodically poled structure
`produces quasi-phase matching with the incident light and modulates the
`wavelength. For example, when red light is incident, blue light is outputted.
`In this configuration, the light used to expose the DNA chip can be selected
`from among a wide range of wavelengths.
`
`[0046]
`
`The invention in claim 12 is a DNA chip reading device according to any of
`claims 8 through 11, wherein the reading head comprises a plurality of
`optical waveguide devices arranged on a single substrate.
`
`[0047]
`
`Because a DNA reading device with this configuration has a reading head
`with a plurality of reading units, several fluorescence intensities can be
`measured during a single scan. This improves the throughput.
`
`[0048]
`
`[Embodiment of the Invention]
`
`The following is an explanation of embodiments of the present invention with
`reference to the drawings.
`
`[1st Embodiment]
`
`FIG. 1 is a cross-sectional view of the DNA chip reading head in the first
`embodiment of the present invention.
`
`[0049]
`
`A laser beam emitted from a semiconductor light source 11 passes through a
`lens 12, is reflected by a dichroic mirror 13, and is focused by an aspherical
`objective lens 14 on a DNA chip 1. The dichroic mirror 13 acts as a half
`mirror on the wavelengths of the light source 11, allowing the wavelengths
`of the fluorescent light to pass through and be read. The dichroic mirror 13
`is a cube with 10 mm sides. The fluorescent light generated by the laser
`beam reflected by the DNA chip 1 passes through an aspherical objective
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`lens 14, passes through the dichroic mirror 13, and is incident on a second
`dichroic mirror 15.
`
`[0050]
`
`The dichroic mirror 15 reflects a laser beam of all wavelengths of the light
`source 11 but allows fluorescent light to pass through. As in the case of the
`other dichroic mirror 13, this mirror is a cube with 10 mm sides. The light
`reflected by the dichroic mirror 15 off the DNA chip 1 is focused by a lens 16
`on a quadripartite light-receiving element 17. The quadripartite light-
`receiving element 17 uses the astigmatic method to detect a focus offset by
`the objective lens 14 on the surface of the DNA chip 1. The detection of a
`focus offset by the astigmatic method is currently used by optical disk
`devices.
`
`[0051]
`
`The fluorescent light passing through the dichroic mirror 15 is focused on a
`pinhole in an aperture 19 by an aspheric imaging lens 18. In the light
`incident on the aspheric imaging lens 18, there are some unwanted
`components such as noise. These unwanted components include light from a
`source other than the light source 11 incident on and reflected by the DNA
`chip 1 as well as other types of ambient light. The aperture 19 is used to
`block these unwanted components.
`
`[0052]
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`The light passing through the pinhole in the aperture 19 is received by a
`light-receiving element 20. The output from the light-receiving element 20 is
`amplified by an amplifier 21 and outputted from the DNA reading head.
`
`[0053]
`
`The lenses 12, 16 used here are aspherical lenses. When aspherical lenses
`are used, the optics do not require multiple lenses and are more compact.
`The diameter of the lenses 12, 14, 16, 18 used here is 6 mm.
`
`[0054]
`
`The driver circuit 23 for the light source 11 and the autofocus circuit 24 are
`arranged on a circuit board 22. The autofocus circuit 24 uses the output
`from the quadripartite light-receiving element 17 to drive a Z-axis actuator
`25 and move the objective lens 14 along the Z-axis to focus the aspherical
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`objective lens 14 on the DNA chip 1. The autofocus operation is conducted
`continuously during measurements.
`
`[0055]
`
`The optics, elements, and circuits for reading a DNA chip are integrated, and
`the DNA chip reading head is housed inside a single case 26. As a result, the
`reader is much more compact and lightweight than a conventional reader.
`The shape and size of the case 26 (that is, the DNA chip reading head) is
`rectangular with a width and depth of 30 mm and a height of 50 mm. The
`weight of the case is approximately 100 g.
`
`[0056]
`
`The DNA chip reading head in the present embodiment is based on a pickup
`head for optical disks. As a result, the device is much smaller and lighter.
`Because an aperture is used, noise is also reduced.
`
`[0057]
`
`When a DNA chip reading head of the present embodiment is mounted on a
`DNA chip reading device of the present invention described below, the
`overall size of the DNA chip reading device can be reduced.
`
`[2nd Embodiment]
`
`FIG. 2 is a perspective view of the DNA chip reading head in the second
`embodiment of the present invention. This DNA chip reading head is
`manufactured using optical waveguide technology. By using an optical
`waveguide element, a compact and lightweight DNA chip reading head can
`be realized.
`
`[0058]
`
`The substrate 27 has a glass layer on top of a Si substrate 27a. The glass
`layer is formed using sputtering, and this becomes an optical waveguide
`27b. A light source 32 with a laser diode is arranged on the end of the
`substrate 27.
`
`[0059]
`
`Photodiodes 28, 29 are arranged on the Si substrate 27a to detect focusing
`errors using the Foucault method. The glass surface of the optical waveguide
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`27b is etched to form a focusing grating coupler 30 and a deflection
`condensing grating 31.
`
`[0060]
`
`The focusing grating coupler 30 couples light of a predetermined wavelength
`incident from the optical waveguide, and this light is emitted into the space.
`The light of a predetermined wavelength incident from the space is coupled
`and guided into the optical waveguide. Light of other wavelengths passes
`through or is reflected. As a result, the grating has a function similar to a
`wavelength filter (low-pass, high-pass, etc.). Here, it couples the wavelength
`of the light from the