Photometric dispensing nozzle unit, photometric dispensing apparatus, and photometric dispensing method

Abstract

A photometric dispensing nozzle unit, a photometric dispensing apparatus, and a photometric dispensing method are for preventing an increase in apparatus scale and have a simple structure to be easily handled. A nozzle performs suction/discharge of gas through a distal end opening and can have a dispensing tip attached thereto. A light guide end portion is provided in the nozzle and can receive or irradiate light at a distal end of the nozzle. A dispensing cylinder has a cylinder having a cavity therein, a plunger that is slidable in the cavity, and a suction/discharge port that performs suction/discharge of gas. A suction/discharge flow path passes through the nozzle and communicates with the suction/discharge port and the distal end opening of the nozzle. A light guide path is optically connected to the light guide end portion through the nozzle but not through the dispensing cylinder.

Claims

1. A photometric dispensing nozzle unit comprising: a nozzle having a distal end opening through which suction/discharge of gas is performed and to which a dispensing tip is attached; a light guide end portion which is provided in the nozzle and in which light is received or irradiated at a distal end of the nozzle; a dispensing cylinder including a cylinder having a cavity therein, a plunger that is slidable in the cavity, and a suction/discharge port through which suction/discharge of gas is performed; a suction/discharge flow path that passes through the nozzle and allows the suction/discharge port to communicate with the distal end opening of the nozzle; and a light guide path optically connected to the light guide end portion through the nozzle without through the dispensing cylinder.

2. The photometric dispensing nozzle unit according to claim 1, further comprising a flow path built-in support member in which the nozzle and the dispensing cylinder are independently and detachably attached and supported in parallel a partial region of the suction/discharge flow path is formed therein.

3. The photometric dispensing nozzle unit according to claim 2, wherein the nozzle has a nozzle lateral hole formed through a side wall thereof, the suction/discharge port is a cylinder lateral hole formed through a side wall of the cylinder, and the partial region of the suction/discharge flow path has a connecting flow path formed so as to allow the nozzle lateral hole of the nozzle attached to the flow path built-in support member to communicate with the cylinder lateral hole of the dispensing cylinder attached to the flow path built-in support member.

4. The photometric dispensing nozzle unit according to claim 3, wherein the flow path built-in support member includes: a flow path built-in support block; a nozzle attachment longitudinal hole and a cylinder attachment longitudinal hole bored in the flow path built-in support block; and the connecting flow path formed in the flow path built-in support block and allowing the nozzle attachment longitudinal hole to communicate with the cylinder attachment longitudinal hole, the nozzle is closely attached to the nozzle attachment longitudinal hole, the dispensing cylinder is closely attached to the cylinder attachment longitudinal hole, and the connecting flow path allows the nozzle lateral hole of the attached nozzle to communicate with the cylinder lateral hole of the attached dispensing cylinder.

5. The photometric dispensing nozzle unit according to claim 4, wherein any one of close contact surfaces between the nozzles and the nozzle attachment longitudinal holes and any one of close contact surfaces between the dispensing cylinders and the cylinder attachment longitudinal holes each have a seal member vertically partitioning each of the close contact surfaces so as to sandwich the cylinder lateral holes and the nozzle lateral holes at upper and lower positions.

6. The photometric dispensing nozzle unit according to claim 3, further comprising a pressure sensor communicating with the distal end opening of the nozzle, wherein the side wall of the nozzle has a second nozzle lateral hole passing through the side wall, the pressure sensor communicates with the distal end opening through the second nozzle lateral hole, the flow path built-in support block of the flow path built-in support member further has a pressure sensor attachment hole with which the pressure sensor is independently and detachably attached, and a pressure sensor flow path allowing the attached pressure sensor to communicate with the second nozzle lateral hole is formed.

7. The photometric dispensing nozzle unit according to claim 1, wherein the cavity of the dispensing cylinder has a large diameter region having a large diameter inner peripheral surface, and a small diameter region formed on the suction/discharge port side of the large diameter region and having a small diameter inner peripheral surface, the plunger has a thick shaft portion that is slidable in the large diameter region, and a thin shaft portion that protrudes from a distal end surface of the thick shaft portion in the axial direction and is slidable in the small diameter region, a play region in which the thick shaft portion is configured to move with a play in the axial direction is formed between the large diameter region and the small diameter region, and the suction/discharge port is formed so as to be located in a cavity ahead of the small diameter region.

8. A photometric dispensing apparatus comprising: one or more container groups each including a reaction container, and a liquid storing unit or a dispensing tip storing unit; one or more photometric dispensing nozzle units each including: a nozzle which performs suction/discharge of gas through a distal end opening and to which a dispensing tip is attached, a dispensing cylinder including a cylinder having a cavity therein and a plunger that slides in the cavity and having a gas suction/discharge port, and a suction/discharge flow path allowing the suction/discharge port to communicate with the distal end opening through the nozzle; a nozzle moving mechanism that is configured to move the nozzle relatively to the container groups; a suction/discharge driving unit that moves the plunger of the dispensing cylinder in a vertical direction and makes it possible for the dispensing tip attached to the nozzle to simultaneously suction liquid from the container groups and to simultaneously discharge liquid to the container groups; a light measuring device that converts at least received light into digital data; and a photometric dispensing control unit that controls a dispensing treatment or a photometric treatment for the nozzle moving mechanism, the suction/discharge driving unit, and the light measuring device, wherein the nozzle has a light guide end portion capable of receiving or irradiating light at a distal end of the nozzle, and a light guide path optically connected to the light guide end portion through the nozzle without through the dispensing cylinder, and the light measuring device is optically connected to the light guide path.

9. The photometric dispensing apparatus according to claim 8, wherein each of the one or more sets of photometric dispensing nozzle units further includes a flow path built-in support body in which the nozzle and the dispensing cylinder are independently and detachably attached and supported in parallel, and a partial region of the suction/discharge flow path is formed therein.

10. The photometric dispensing apparatus according to claim 9, wherein the nozzle has a nozzle lateral hole formed through a side wall thereof, the suction/discharge port is a cylinder lateral hole formed through a side wall of the cylinder, and the partial region of the suction/discharge flow path is a connecting flow path allowing the nozzle lateral hole of the nozzle attached to and supported by the flow path built-in support body to communicate with the cylinder lateral hole of the dispensing cylinder attached to the flow path built-in support body and supported thereby so as to face the nozzle lateral hole.

11. The photometric dispensing apparatus according to claim 8, wherein the flow path built-in support body includes: a flow path built-in support block; one or more sets of a nozzle attachment longitudinal hole and a cylinder attachment longitudinal hole bored in the flow path built-in support block; and the connecting flow path formed in the flow path built-in support block and allowing the nozzle attachment longitudinal hole to communicate with the cylinder attachment longitudinal hole in each of the sets, the nozzle is closely attached to the nozzle attachment longitudinal hole, the dispensing cylinder is closely attached to the cylinder attachment longitudinal hole, and the connecting flow path allows the nozzle lateral hole of the attached nozzle to communicate with the cylinder lateral hole of the attached dispensing cylinder.

12. The photometric dispensing apparatus according to claim 8, wherein the flow path built-in support block of the flow path built-in support body further includes a pressure sensor communicating with the distal end opening of each of the nozzles, the side wall of the nozzle has a second nozzle lateral hole passing through the side wall, the pressure sensor communicates with the distal end opening through the second nozzle lateral hole, the flow path built-in support block further has a pressure sensor attachment hole with which the pressure sensor is independently and detachably attached, and a pressure sensor flow path allowing the attached pressure sensor to communicate with the second nozzle lateral hole is formed.

13. The photometric dispensing apparatus according to claim 8, wherein the cavity of the dispensing cylinder has a large diameter region having a large diameter inner peripheral surface and a small diameter region provided on the suction/discharge port side of the large diameter region and having a small diameter inner peripheral surface, the plunger has a thick shaft portion provided so as to be slidable in the large diameter region and a thin shaft portion protruding from a distal end surface of the thick shaft portion in the axial direction and provided so as to be slidable in the small diameter region, a play region in which the thick shaft portion is configured to move with a play in the axial direction is formed between the large diameter region and the small diameter region, the suction/discharge port is located in a cavity ahead of the small diameter region, the photometric dispensing control unit includes a minute amount/large amount judgement and instruction means that determines, in a case where there is an instruction for suction/discharge of a predetermined amount of liquid to the dispensing tip, whether the predetermined amount is a minute amount or a large amount, and instructs the suction/discharge driving unit to locate the thin shaft portion of the plunger of the dispensing cylinder in a minute amount suction/discharge section in which the thin shaft portion is slidable in the small diameter region and to move the thin shaft portion by a moving distance according to the predetermined amount in a case where the judgement result is a minute amount, and instructs the suction/discharge driving unit to locate the thick shaft portion of the plunger in a large amount suction/discharge section in which the thick shaft portion is slidable in the large diameter region and to move the thick shaft portion by a moving distance according to the predetermined amount in a case where the judgement result is a large amount.

14. A photometric dispensing method comprising: a moving step of relatively moving nozzles of one or more photometric dispensing nozzle units including the nozzles which perform suction/discharge of gas to one or more container groups each including a reaction container and a liquid storing unit or a dispensing tip storing unit through a distal end opening, and to which dispensing tips are attached, a dispensing cylinder including a cylinder having a cavity therein and a plunger that slides in the cavity and having a gas suction/discharge port, and a suction/discharge flow path allowing the suction/discharge port to communicate with the distal end opening through the nozzles by the nozzle moving mechanism; an attachment step of attaching the dispensing tips to the nozzles by the nozzle moving mechanism; a suction/discharge step of simultaneously performing suction/discharge of liquid stored in the container groups to the dispensing tips by the suction/discharge driving unit; a removal step of removing the dispensing tips from the nozzles; and a light measuring step of performing measurement by connecting distal end portions of the nozzles to an opening of the reaction container directly or indirectly by the nozzle moving mechanism, and optically connecting a light measuring device with the reaction container through a light guide path optically connected to a light guide end portion formed in the nozzles through the nozzles without through the light guide end portion or the dispensing cylinder.

15. The photometric dispensing method according to claim 14, wherein each of the one or more sets of photometric dispensing nozzle units includes a flow path built-in support body in which the nozzle and the dispensing cylinder are independently and detachably attached and supported in parallel, and a partial region of the suction/discharge flow path is formed therein, and the method further comprises a nozzle unit attachment step of attaching the nozzles and the dispensing cylinders to the flow path built-in support body.

16. The photometric dispensing method according to claim 14, wherein the cavity of the dispensing cylinder has a large diameter region having a large diameter inner peripheral surface and a small diameter region provided on the suction/discharge port side of the large diameter region and having a small diameter inner peripheral surface, the plunger has a thick shaft portion provided so as to be slidable in the large diameter region and a thin shaft portion protruding from a distal end surface of the thick shaft portion in the axial direction and provided so as to be slidable in the small diameter region, a play region in which the thick shaft portion is configured to move with a play in the axial direction is formed between the large diameter region and the small diameter region, and the suction/discharge port is located in a cavity ahead of the small diameter region, the photometric dispensing method further comprises a judgement step of judging whether a predetermined amount is a minute amount or a large amount when suction/discharge of the predetermined amount of liquid is instructed to the dispensing tip, in the attachment step, a minute amount dispensing tip is attached in a case where the predetermined amount is judged to be a minute amount, and a large amount dispensing tip is attached to the nozzle in a case where the predetermined amount is judged to be a large amount, and the suction/discharge step includes: a minute amount suction/discharge step of causing the dispensing tips to perform suction/discharge of the minute amount of liquid by locating the thin shaft portion of the plunger of the dispensing cylinder in a minute amount suction/discharge section in which the thin shaft portion is slidable in the small diameter region and sliding the thin shaft portion by a distance according to the predetermined amount in a case where the predetermined amount is judged to be a minute amount; and a large amount suction/discharge step of causing the dispensing tips to perform suction/discharge of the large amount of liquid by locating the thick shaft portion of the plunger in a large amount suction/discharge section in which the thick shaft portion is slidable in the large diameter region and sliding the thick shaft portion by a distance according to the predetermined amount in a case where the predetermined amount is judged to be a large amount.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a block diagram of a photometric dispensing apparatus according to a first embodiment of the present invention.

(2) FIG. 2 is a perspective view of the photometric dispensing apparatus according to the first embodiment of the present invention.

(3) FIG. 3 is a partially transparent side view of the apparatus illustrated in FIG. 2.

(4) FIG. 4 is a plan view of the apparatus illustrated in FIG. 2.

(5) FIG. 5 is a partially enlarged perspective view illustrating a main part of a nozzle head in FIGS. 2 and 3.

(6) FIG. 6 is a perspective view excluding some components in FIG. 5.

(7) FIG. 7 is a view illustrating tip removing operation based on the partially enlarged side view of FIG. 3.

(8) FIG. 8 is an exploded perspective view of a nozzle of a photometric dispensing nozzle unit according to the first embodiment of the present invention.

(9) FIG. 9 is a cross-sectional view of a dispensing cylinder of the photometric dispensing nozzle unit according to the first embodiment of the present invention.

(10) FIG. 10 illustrates a partial cross-sectional perspective view of FIG. 5 and an enlarged cross-sectional side view thereof.

(11) FIG. 11 is a cross-sectional perspective view illustrating operation of the dispensing cylinder according to the first embodiment of the present invention.

(12) FIG. 12 is an operation explanatory view of the photometric dispensing nozzle unit according to the first embodiment of the present invention.

(13) FIG. 13 illustrates a perspective view of a dispensing cylinder of a photometric dispensing nozzle unit according to a second embodiment of the present invention and a cross-sectional perspective view thereof.

(14) FIG. 14 is a table illustrating examples of results of a distilled water dispensing experiment of the photometric dispensing apparatus according to the first embodiment of the present invention.

(15) FIG. 15 is a table illustrating examples of results of an experiment of the photometric dispensing apparatus according to the first embodiment of the present invention for a predetermined fluorescent solution.

(16) FIG. 16 illustrates a table and a graph illustrating examples of results of an experiment of the photometric dispensing apparatus according to the first embodiment of the present invention for a fluorescent solution having a predetermined concentration.

DESCRIPTION OF EMBODIMENTS

(17) Subsequently, embodiments of the present invention will be described with reference to the drawings. Note that the embodiments should not be construed as limiting the present invention unless otherwise specified. In the embodiments or embodiment examples, the same reference numeral is used to denote the same part, and description thereof is omitted.

(18) FIG. 1 illustrates a block diagram of a photometric dispensing apparatus 100 according to a first embodiment of the present invention using a photometric dispensing nozzle unit according to the first embodiment.

(19) The photometric dispensing apparatus 100 roughly includes: a stage 20 in which a plurality of (n in this example, n≥1, corresponding to lanes in FIGS. 15 and 16) container groups 20.sub.i (i=1, . . . n) is arranged; a nozzle head 50 including n sets of photometric dispensing nozzle units 10.sub.1 to 10.sub.n each at least including nozzles 11.sub.1 to 11.sub.n to which large amount dispensing tips 211.sub.1 to 211.sub.n or minute amount dispensing tips 212.sub.1 to 212.sub.n can be attached and which can receive or irradiate light at distal ends thereof and dispensing cylinders 12.sub.1 to 12.sub.n which communicate with the nozzles 11.sub.1 to 11.sub.n and perform suction/discharge of gas to the dispensing tips; a nozzle head moving mechanism 51 that can move the nozzle head 50 relatively to the container groups 20, for example, in an X-axis direction; a CPU+program+memory 60 including, for example, a CPU that performs various controls, a ROM, a RAM, various external memories, a communication function such as LAN, and a program stored in the ROM or the like as the photometric dispensing control unit; and an operation panel 65 including a display unit such as a liquid crystal display and an operation unit such as operation keys or a touch panel.

(20) The nozzles 11.sub.1 to 11.sub.n provided in the respective sets of photometric dispensing nozzle units 10.sub.1 to 10.sub.n include light guide end portions 32.sub.1 to 32.sub.n capable of receiving or irradiating light at distal ends of the nozzles 11.sub.1 to 11.sub.n, and light guide paths 31.sub.1 to 31.sub.n passing through the nozzles 11.sub.1 to 11.sub.n and optically connected to the light guide end portions 32.sub.1 to 32.sub.n, and the dispensing cylinder 12.sub.1 to 12.sub.n include cylinders each having a cavity therein, plungers provided so as to be slidable in the cavity, and a suction/discharge port bored in each of the cylinders, and further include a suction/discharge flow path passing through the nozzles 11.sub.1 to 11.sub.n and allowing the suction/discharge port to communicate with distal end openings of the nozzles 11.sub.1 to 11.sub.n.

(21) The nozzle head 50 further includes: a flow path built-in support body 70 in which the one or more sets of nozzles 11.sub.1 to 11.sub.n and the dispensing cylinders 12.sub.1 to 12.sub.n are independently and detachably attached and supported in parallel, and connecting flow paths 71.sub.1 to 71.sub.n are formed therein as a partial region of the suction/discharge flow path; a suction/discharge driving unit 53 that moves the plunger of the dispensing cylinders 12.sub.1 to 12.sub.n in the vertical direction and makes simultaneous suction/discharge of liquid by the dispensing tips 211.sub.1 to 211.sub.n and 212.sub.1 to 212.sub.n attached to the nozzles 11.sub.1 to 11.sub.n to the container groups 20.sub.1 to 20.sub.n possible; a tip removing mechanism 59 that can remove the dispensing tips 211.sub.1 to 211.sub.n and 212.sub.1 to 212.sub.n attached to the nozzles 11.sub.1 to 11.sub.n using the suction/discharge driving unit 53; a nozzle Z-axis moving mechanism 58 that can move the nozzles 11.sub.1 to 11.sub.n in the Z-axis direction; and a magnetic force unit 57 that can apply a magnetic field to the inside of the dispensing tips 211.sub.1 to 211.sub.n and 212.sub.1 to 212.sub.n in which magnets are attached to the nozzles by providing the magnets so as to be movable forward and backward with respect to the dispensing tips 211.sub.1 to 211.sub.n and 212.sub.1 to 212.sub.n.

(22) The nozzle head 50 further includes a light measuring device 40.

(23) The light measuring device 40 includes: a connection end array 30 that arranges and supports a plurality of (n in this example) connection ends 34.sub.1 to 34.sub.n provided so as to correspond to the light guide end portions 32.sub.1 to 32.sub.n, having distal ends thereof at the light guide end portions 32.sub.1 to 32.sub.n, and having rear ends of optical fibers (bundles) as light guide portions 31.sub.1 to 31.sub.n along a predetermined path (a linear path in the Y-axis direction in this example) formed on a horizontal surface as an array surface so as to be integrated at an interval narrower than an interval between the light guide end portions 32.sub.1 to 32.sub.n; and for example, m types (six types in this example) of specific wavelength measuring devices 40.sub.j (j=1, . . . m, omitted below) that can receive fluorescence having m specific wavelengths or light within m specific wavelength bands, and can irradiate excitation light having m specific wavelengths or excitation light within m specific wavelength bands, irradiated for emission of the light. Note that in a case where the optical fibers (31.sub.1 to 31.sub.n) include an irradiation optical fiber (bundle) 35 and a light receiving optical fiber (bundle) 36, the connection ends 34.sub.1 to 34.sub.n as rear ends of the optical fibers (31.sub.1 to 31.sub.n) include first connection ends (for irradiation) and second connection end (for light reception), and arranged and supported along a linear path in the Y-axis direction. In this case, each of the light guide end portions 32.sub.1 to 32.sub.n corresponds to a pair of the light irradiating end and the light receiving end.

(24) Each specific wavelength measuring device 40.sub.j has a measurement end 44.sub.j provided in proximity (non-contact) or in contact with the array surface, and sequentially connectable to the connection end 34.sub.1 along the predetermined path (linear path along the Y-axis direction). Each measurement end 44.sub.j has two measurement ends of a first measurement end 42.sub.j and a second measurement end 43.sub.j arranged in the Y-axis direction in a case where light emission is fluorescence. These measurement ends are arranged, for example, on a measurement end array surface. The first measurement end 42.sub.j is optically connected to an irradiation source provided in each specific wavelength measuring device 40.sub.j. The second measurement end 43.sub.j is optically connected to a photoelectric conversion unit such as a photomultiplier provided in the specific wavelength measuring device 40.sub.j. In a case where light emission is chemiluminescence or the like, it is only required to provide at least the second measurement end 43.sub.j. In this case, the first connection ends of the rear ends of the irradiation optical fibers (bundle) 35 are arranged on the connection end array surface of the connection end array 30 so as to be connectable to the first measurement end 42.sub.j. The second connection ends of the rear ends of the light receiving optical fibers (bundle) 36 are arranged on the connection end array surface of the connection end array 30 so as to be connectable to the second measurement end 43.sub.j.

(25) Furthermore, the nozzle head 50 includes an array Y-axis moving mechanism 41 as an array moving mechanism that moves the connection end array 30 on the nozzle head 50 in the Y-axis direction by bringing the connection end array surface and the measurement end array surface in proximity (non-contact) or sliding the connection end array surface and the measurement end array surface so as to sequentially connect the connection ends 34.sub.1 arranged on the connection end array surface of the connection end array 30 to the measurement ends 44.sub.j arranged on the measurement end array surface.

(26) The stage 20 include a plurality of (eight in this example) container groups 20.sub.1 corresponding to the respective nozzles that one nozzle enters and the other nozzles do not enter. Each of the container groups 20.sub.1 includes: a liquid storing unit group 27.sub.1 including a plurality of storing units storing or capable of storing a reagent solution or the like; a tip or the like storing unit group 21.sub.1 including a sealing lid storing unit that stores the one or more light transmitting sealing lids 25.sub.1 detachably attached to the nozzles, and storing a plurality of large amount dispensing tips 211.sub.1, and minute amount dispensing tips 212.sub.1 detachably attached to the nozzles, and a piercing tip; and reaction containers 23.sub.1 to 23.sub.n capable of controlling temperature of a PCR tube or the like. The liquid storing unit group 27.sub.1 includes one or more liquid storing units that store at least a magnetic particle suspension, and two or more liquid storing units that store a separation/extraction solution used for separation and extraction of a nucleic acid or fragments thereof. Furthermore, the liquid storing unit group 27.sub.1 stores an amplification solution used for amplification of a nucleic acid and a sealing solution for sealing the amplification solution stored in the PCR tube 231.sub.1 as the reaction container in the PCR tube 231.sub.1.

(27) FIGS. 2 to 4 illustrate a perspective view, a side view, and a plan view in which the photometric dispensing apparatus 100 illustrated in FIG. 1 is further embodied (in a case of n=8 and m=6), respectively

(28) On the stage 20, four cartridge containers 201.sub.1 to 204.sub.1 are loaded in a vertical row for each of the container groups 20.sub.1 to 20.sub.n arranged in n rows (eight rows in this example), and cartridge containers 205 to 207 that store three samples are loaded in parallel in a lateral direction.

(29) As illustrated in FIG. 2, the nozzle head moving mechanism 51 includes: a drive motor 51a attached to a pedestal on which the stage 20 is placed; a pulley 51b rotationally driven by the drive motor and a pulley 51c to make a pair with the pulley 51b; a timing belt 51d that is stretched by the two pulleys 51b and 51c and can travel in the X-axis direction; and a leg 51e attached to the timing belt 51d and supporting a frame 50a of the nozzle head 50. The leg 51e is movably supported in the X-axis direction, for example, by a linear motion guiding device 51f, and a lower side of the leg 51e is connected to the timing belt 51d.

(30) The nozzle head 50 includes the photometric dispensing nozzle units 10.sub.1 to 10.sub.n including the nozzles 11.sub.1 to 11.sub.n (n=8 in this example) and dispensing cylinders 12.sub.1 to 12.sub.n (n=8 in this example) independently and detachably attached to the flow path built-in support block 76 of the flow path built-in support body 70 and supported thereby in parallel, respectively, and upper sides of the dispensing cylinders 12.sub.1 to 12.sub.n are attached to a cylinder attachment body 73 of the flow path built-in support body 70. Pressure sensors 13.sub.1 to 13.sub.n (n=8 in this example) are provided in the photometric dispensing nozzle units 10.sub.1 to 10.sub.n (n=8 in this example), respectively. The pressure sensors 13.sub.1 to 13.sub.n are connected to a pressure sensor substrate 13a.

(31) In the nozzle head 50, the suction/discharge driving unit 53 includes: a suction motor 53a attached to a mount 53e; a ball screw 53b rotationally driven by the motor 53a; a nut portion 53c screwed with the ball screw 53b and movable in the vertical direction; and a suction/discharge driving member 53d that is connected to the nut portion 53c and can raise the plunger 12a of the dispensing cylinders 12.sub.1 to 12.sub.n. The suction/discharge driving member 53d has a hole or a gap having a size that is engageable with a flange 12t but does not come in contact with the plunger 12a. In the nozzle head 50, n (eight in this example) magnetic poles of permanent magnets are arranged as the magnetic force unit 57 in a row in the Y-axis direction.

(32) As illustrated in FIG. 3, in the nozzle head 50, the nozzle Z-axis moving mechanism 58 includes a Z-axis drive motor 58a placed on the frame 50a, a ball screw 58b rotationally driven by the Z-axis drive motor 58a, a nut portion 58c screwed with the ball screw 58b, and a wall-shaped Z-axis moving body 58d connected to the nut portion 58c.

(33) To the Z-axis moving body 58d, the suction motor 53a, the motor mount 53e, the cylinder attachment body 73 that attaches the dispensing cylinders 12.sub.1 to 12.sub.8 on upper sides thereof, and the n sets (eight sets in this example) of the nozzles 11.sub.1 to 11.sub.n (n=8 in this example) and the dispensing cylinders 12.sub.1 to 12.sub.n are independently and detachably attached and supported in parallel, and the flow path built-in support block 76 of the flow path built-in support body 70 having the connecting flow paths 71.sub.1 to 71.sub.n (n=8 in this example) as a partial region of the suction/discharge flow path therein is attached.

(34) As illustrated in FIG. 4, the cartridge container 201.sub.i (i=1, . . . 8) includes the tip or the like storing unit 21.sub.i that stores four tips, for example, a piercing tip, one large amount dispensing tip 211.sub.i, and two minute amount dispensing tips. The cartridge container 202.sub.i includes eight liquid storing units 27.sub.i that store an extraction reagent or the like, a reaction container 23.sub.i that can be set to a constant temperature condition, and a liquid storing unit that can be set to a constant temperature condition and stores a product. The cartridge container 203.sub.i includes three liquid storing units 27.sub.i storing an amplification reagent. The cartridge container 204.sub.i includes a sealing lid storing unit as the tip or the like storing unit 21.sub.i that stores the PCR tube (23.sub.i) and the sealing lid 25. Each of the cartridge containers 205 and 206 includes a sample tube 26.sub.i that stores a sample, and the cartridge container 207 stores residual liquid.

(35) In the nozzle head 50, the measuring device 40 is attached to the nozzle head frame 50a such that the m types (six types in this example) of specific wavelength measuring devices 40.sub.1 to 40.sub.m (m=8 in this example) are arranged in the Y-axis direction with the measurement ends 44.sub.1 to 44.sub.m (m=6 in this example, and one is hidden in the connection end array 30) on an upper side. The connection end array 30 in which the connection ends 34.sub.1 to 34.sub.n (n=8 in this example) are arranged in the Y-axis direction is provided so as to be movable in the Y-axis direction on an upper side of the specific wavelength measuring devices 40.sub.1 to 40.sub.m. As described above, each of the connection ends 34.sub.1 to 34.sub.n includes a first connection end as a rear end of the irradiation optical fiber 35 and a second connection end as a rear end of the light receiving optical fiber 36. Each of the measurement ends 44.sub.1 to 44.sub.m includes a first measurement end 42.sub.i and a second measurement end 43.sub.i. The first measurement ends 42.sub.i are optically connected to an irradiation source of the excitation light, and can be sequentially connected to the first connection ends. The second measurement ends 43.sub.i are optically connected to the photoelectric conversion unit and arranged in a row in the Y-axis direction so as to be sequentially connectable to the second connection ends.

(36) FIG. 5 is a main part of the nozzle head 50 of the photometric dispensing apparatus 100 illustrated in FIGS. 2 and 3, and illustrates the cylinder attachment body 73 and the flow path built-in support block 76 of the flow path built-in support body 70 attached to the Z-axis moving body 58d, n sets (n=8) of the nozzles 11.sub.1 to 11.sub.n attached thereto, the dispensing cylinders 12.sub.1 to 12.sub.n, the pressure sensors 13.sub.1 to 13.sub.n, and the tip removing mechanism 59.

(37) Eight dispensing cylinders 12.sub.1 to 12.sub.n (n=8) are attached to the cylinder attachment body 73 with the plunger 12a on an upper side, and are supported such that lower end portions thereof are in close contact with cylinder attachment longitudinal holes 75.sub.1 to 75.sub.n (n=8) of the flow path built-in support body 70. These dispensing cylinders 12.sub.1 to 12.sub.n are screwed with the cylinder attachment body 73 by a ring-shaped screw 12v.

(38) The flow path built-in support body 70 communicates with the nozzles 11.sub.1 to 11.sub.n through a conduit 72a communicating with a flow path having the n pressure sensors 13.sub.1 to 13.sub.n therein. The pressure sensors 13.sub.1 to 13.sub.n are connected to the pressure sensor substrate 13a attached to the cylinder attachment body 73.

(39) As illustrated in FIG. 5, the tip removing mechanism 59 includes: two injection pins 59b and 59b that can move downward by being pressed due to further lowering of the suction/discharge driving member 53d of the suction/discharge driving unit 53 beyond the suction/discharge section; and a tip removing member 59a connected to lower ends of the injection pins 59b, provided below the flow path built-in support block 76, and having holes formed so as to surround the nozzles 11.sub.1 to 11.sub.n and to be movable in the axial direction, and having inner diameters larger than the nozzles 11.sub.1 to 11.sub.n but smaller than the largest outer diameter of the dispensing tips 211.sub.1 to 211.sub.n and 212.sub.1 to 212.sub.n.

(40) Furthermore, the tip removing mechanism 59 includes: a head 59d provided at an upper end of the inject pin 59b and pressed by the suction/discharge driving member 53d; and a spring 59c formed so as to surround the inject pin 59b and biasing the head 59d upward such that one end thereof is attached to the cylinder attachment body 73, and the other end thereof reaches the head 59d.

(41) FIG. 6 clearly illustrates the flow path built-in support body 70 including the cylinder attachment body 73 illustrated in FIG. 5. In the cylinder attachment body 73, n (n=8 in this example) longitudinal holes are arranged in a row in a longitudinal direction, the eight dispensing cylinders 12.sub.1 to 12.sub.n (n=8) are inserted from upper sides thereof into the longitudinal holes with the plunger 12a facing upward, and a lower end portion is supported so as to be closely fitted to the cylinder attachment longitudinal holes 75.sub.1 to 75.sub.n (n=8) of the flow path built-in support body 70. These dispensing cylinders 12.sub.1 to 12.sub.n are attached to the cylinder attachment body 73 by the ring-shaped screw 12v. The cylinder attachment body 73 has, in addition to n (n=8) longitudinal holes arranged in a row and attaching the dispensing cylinders 12.sub.1 to 12.sub.n, two longitudinal holes 59e at both ends located outside the row and protruding in the X-axis direction by a predetermined distance. The inject pin 59b passes through the longitudinal hole 59e.

(42) As illustrated in FIG. 6, in the flow path built-in support body 70, n (n=8 in this example) nozzle attachment longitudinal holes 74.sub.1 to 74.sub.n (n=8) are arranged in a row such that the nozzles 11.sub.1 to 11.sub.n can be inserted from lower sides thereof and can be screwed with a ring-shaped screw 11g to be attached, and pressure sensor flow paths 72.sub.1 to 72.sub.n are further formed.

(43) FIG. 7 illustrates the structure of each of the nozzles 11.sub.1 to 11.sub.8 included in the photometric dispensing nozzle units 10.sub.1 to 10.sub.n.

(44) The nozzle 11.sub.i (i=1 in this example) includes: a substantially tubular nozzle main body 11b having a distal end opening 11a at a distal end thereof; the optical system unit 11p inserted into the nozzle main body 11b; and a ring screw 11r used for attaching the nozzle 11 to the flow path built-in support body 70 by screwing.

(45) A distal end portion 11q of the nozzle 11 can be attached to the attachment openings of the dispensing tips 211 and 212 by fitting, has a nozzle lateral hole 11c passing through a side wall with a close contact surface, and has O-rings 11k and 111 provided so as to sandwich the nozzle lateral hole 11c in the vertical direction and so as to surround the axis along an outer periphery thereof.

(46) The optical system unit 11p includes: a rod lens as the light guide end portion 32.sub.i provided at a distal end thereof; the light guide path 31 including the irradiation optical fiber 35 and the light receiving optical fiber 36 optically connected to the rod lens (32.sub.i) at an end surface thereof; a ferrule unit 11u as the light guide path end solid member through which the light guide path 31 passes and which is inserted and fitted into the nozzle main body 11b; a lens holding tube 11g fitted and attached to a holding tube fitting portion 11f of the ferrule unit 11u and holding the lens (32.sub.i) therein; and a cut-out surface 11e formed so as to cut out an outer peripheral surface of the cylindrical ferrule unit 11u in the axial direction. Note that one end of the irradiation optical fiber 35 and one end of the light receiving optical fiber 36 are optically connected to the rod lens (32.sub.i). The other end of the irradiation optical fiber 35 and the other end of the light receiving optical fiber 36 are arranged in a row in the Y-axis direction in the connection end array 30 as a first connection end and a second connection end so as to be optically connectable to the second measurement end 43.sub.j and the first measurement end 42.sub.j, respectively (see FIGS. 4 and 10).

(47) A flange 11v is provided on an outer peripheral surface of the ferrule unit 11u. The ferrule unit 11u is fixed to the nozzle main body 11b such that the ferrule unit 11u does not move in the nozzle 11.sub.i by a screw 11w screwed with a screw hole 11s bored in the nozzle main body 11b.

(48) FIG. 8 illustrates a cross section of the dispensing cylinder 12 in a case where a lower end portion 12d described later is removed.

(49) The dispensing cylinder 12 includes: a cylinder 12b having a cavity (12c, 12r, 12q, 12p) therein; a lower end portion 12d (see FIG. 10) located at a lower end of the cylinder 12b, having a cylinder lateral hole 12e as a gas suction/discharge port, and attaching the dispensing cylinder 12.sub.8 to the flow path built-in support block 76 by being inserted into the cylinder attachment longitudinal hole 75.sub.8 from a lower side of the flow path built-in support block 76 and screwing with the cylinder 12b inserted from an upper side of the cylinder attachment longitudinal hole 75.sub.8; and a plunger 12a provided so as to be slidable in the cavity (12c, 12r, 12q, and 12p) in the axial direction, located outside the cylinder 12b, and having a flange 12t engaged with the suction/discharge driving member 53d (see FIG. 9) driven by a stepping motor or the like.

(50) The cavity (12c, 12r, 12q, 12p) formed in the cylinder 12b has a large diameter region 12p having a large diameter inner peripheral surface, and a small diameter region 12c formed on the gas suction/discharge port side of the large diameter region and having a small diameter inner peripheral surface. Between the large diameter region 12p and the small diameter region 12c, there is a play region 12q which has a maximum inner diameter larger than the large diameter and in which the thick shaft portion 12h does not slide. These regions are formed coaxially. The cavity 12r is a portion to which the lower end portion 12d is inserted and attached (see FIG. 10).

(51) The plunger 12a includes: the thick shaft portion 12h provided coaxially with the cavity (12c, 12r, 12q, 12p) of the cylinder 12b formed in the axial direction of the cavity (12c, 12r, 12q, 12p) so as to be slidable in the large diameter region 12p through an opening 12u formed at the other end of the cylinder 12b; and a thin shaft portion 12f protruding from a distal end surface of the thick shaft portion 12h in the axial direction and provided so as to be slidable in the small diameter region 12c.

(52) Furthermore, in the dispensing cylinder 12.sub.8 according to the present embodiment, a seal member 12g (packing or the like) is provided in a peripheral direction on an inner peripheral surface of an upper end portion of the small diameter region 12c, and a seal member 12k is provided in a peripheral direction on an outer peripheral surface of the thick shaft portion 12h. The dispensing cylinder 12 includes a coiled spring 12s having one end attached to an annular groove 121 bored in an upper end surface of the large diameter region 12p, and having the other end wound around the plunger 12a so as to stretch the thick shaft portion 12h. The thick shaft portion 12h is pressed against a step at a boundary between the small diameter region 12c which is a bottom dead center and the play region 12q (FIG. 8(a)). The step protrudes in an inward direction toward the lower direction. FIG. 8(b) illustrates a state in which the plunger 12a is raised, the thin shaft portion 12f is withdrawn from the small diameter region 12c, and the thick shaft portion 12h slides with the large diameter region 12p.

(53) In this case, a length (d0) of the play region 12q in the axial direction satisfies d0+d4>d1+d3 if a length from a distal end surface of the thin shaft portion 12f to a distal end surface of the thick shaft portion in the axial direction is represented by d3, a length from a distal end surface of the thick shaft portion 12h to a sealing position of the seal member 12k is represented by d1, and a distance to a sealing position of the seal member 12g in the small diameter region 12c is represented by d4.

(54) FIG. 9 illustrates in detail the suction/discharge driving unit 53 and the tip removing mechanism 59 for the dispensing cylinder 12.sub.8 of the photometric dispensing nozzle unit 10.sub.8 and illustrates operation thereof.

(55) FIG. 9(a) illustrates a state where the plunger 12a of the dispensing cylinder 12.sub.8 is at a bottom dead center of a stroke thereof. The suction/discharge driving member 53d of the suction/discharge driving unit 53 is not engaged with the flange 12t of the plunger 12a and is located below the flange 12t. The position of the suction/discharge driving member 53d is above the head 59d of the inject pin 59b of the tip removing mechanism 59 and is not in contact with the head 59d. Therefore, the tip removing member 59a is biased upward by the spring 59c, and therefore is located above the distal end portion 11q of the nozzle 11.sub.8.

(56) FIG. 9(b) illustrates a state where the plunger 12a of the dispensing cylinder 12.sub.8 is raised to suck gas from the distal end opening 11a of the nozzle 11.sub.8, and illustrates a state where the suction/discharge driving member 53d of the suction/discharge driving unit 53 is engaged with the flange 12t of the plunger 12a to raise the plunger 12a. Therefore, the suction/discharge driving member 53d is further separated upward from the head 59d of the tip removing mechanism 59. The tip removing member 59a is located above the distal end portion 11q as in the case of FIG. 9(a).

(57) FIG. 9(c) illustrates a state where the suction/discharge driving member 53d is further lowered below the position of FIG. 9(a). In this case, the plunger 12a is disengaged from the flange 12t, and the plunger 12a stays at a bottom dead center thereof. However, the suction/discharge driving member 53d pushes down the head 59d of the tip removing mechanism 59, and therefore pushes down the injection pin 59b and the tip removing member 59a at a lower end thereof to remove the dispensing tips 211.sub.8 and 212.sub.8 that should be attached to the distal end portion 11q of the nozzle 11 from the nozzle 11.

(58) FIGS. 10(a) and 10(b) illustrate the nozzle 11.sub.8, the dispensing cylinder 12, and flow paths 71.sub.8 and 72.sub.8 formed in the flow path built-in support body block 76 to which these are attached, forming the photometric dispensing nozzle unit 10.sub.8 according to the first embodiment of the present invention.

(59) The dispensing cylinder 12.sub.8 according to the present embodiment includes: a cylinder 12b having a cavity (12c, 12q, 12p) therein; a lower end portion 12d attached to a lower end of the cylinder 12b and attaching the dispensing cylinder 12.sub.8 to the flow path built-in support block 76 by being inserted into the cylinder attachment longitudinal hole 75.sub.8 from a lower side of the flow path built-in support block 76 and screwing with the cylinder 12b inserted from an upper side of the cylinder attachment longitudinal hole 75.sub.8; and a plunger 12a provided so as to be slidable in the cavity (12c, 12r, 12q, 12p) in the axial direction, located outside the cylinder 12b, and having a flange 12t engaged with the suction/discharge driving member 53d driven by a stepping motor or the like.

(60) The cavity (12c, 12q, 12p) has the large diameter region 12p having a large diameter inner peripheral surface and the small diameter region 12c formed on the cylinder lateral hole 12e side as the suction/discharge port of the large diameter region 12p and having a small diameter inner peripheral surface. Here, the small diameter region 12c is formed in the lower end portion 12d, and the cylinder lateral hole 12e as the suction/discharge port is bored below the small diameter region 12c.

(61) A seal member 12o is provided at an opening edge of each of the cylinder attachment longitudinal holes 75.sub.1 to 75.sub.8 of the flow path built-in support block 76.

(62) Meanwhile, the nozzle 11.sub.8 is inserted into the nozzle attachment longitudinal hole 74.sub.8 of the flow path built-in support body 70 from a lower side and is attached by the ring-shaped screw 11g. Therefore, the dispensing cylinder 12.sub.8 and the nozzle 11.sub.8 are detachable independently and supported in parallel.

(63) The nozzle lateral hole 11c as the vent hole formed so as to pass through a side wall on which a close-contact surface of the nozzle main body 11b of the attached nozzle 11.sub.8 is formed communicates with the cylinder lateral hole 12e as the suction/discharge port through the connecting flow path 71.sub.8 formed in the flow path built-in support block 76. In the nozzle main body 11, a second nozzle lateral hole 11d formed so as to pass through the side wall at a position facing the nozzle lateral hole 11c communicates with the pressure sensor flow path 72.sub.8 formed in the flow path built-in support block 76 and a connecting portion 72b to which the pressure sensor 13.sub.8 is attached.

(64) The cut-out surface 11e formed on an outer peripheral surface of the ferrule unit 11u so as to cut out the outer peripheral surface is formed so as to extend in the axial direction from a distal end side to a position exceeding the nozzle lateral hole 11c but not exceeding the length of the nozzle main body 11b. Also on the opposite side of the axis, a similar cut-out surface is formed so as to extend in the axial direction to a position exceeding the second nozzle lateral hole 11d corresponding to the vent hole but not exceeding the length of the nozzle main body 11b. Therefore, a gap between each of the cut-out surfaces 11e and an inner peripheral surface of the nozzle main body 11b communicate with each of the nozzle lateral holes 11c and the second nozzle lateral holes 11d. Furthermore, the gap communicates with a gap over the entire periphery surrounded by an outer peripheral surface of the lens holding tube 11g and the inner peripheral surface of the nozzle main body 11b, and therefore communicates with the distal end opening 11a. The gap corresponds to the gap portion. Therefore, a flow path communicating with a portion from the distal end opening 11a to a gap in the nozzle main body 11b, the nozzle lateral hole 11c, the connecting flow path 71.sub.8, and the cylinder lateral hole 12e as the suction/discharge port corresponds to a suction/discharge flow path. A partial region of the flow path corresponds to the connecting flow path 71.sub.8 formed inside the flow path built-in support block 76.

(65) As described above, the lateral holes 11c and 11d are vertically sandwiched by the O-rings 11k and 11.sub.1 to prevent leakage of gas passing between fitting surfaces and to improve airtightness. In addition, an O-ring 11h is provided along an inner peripheral surface of the nozzle main body 11b in order to prevent gas leakage between the fitting surfaces of the ferrule unit 11u inserted and fitted into the nozzle 11.sub.8. With the nozzle according to the present embodiment, it is possible to form and fix a flow path easily because the flow path can be formed by not processing the nozzle main body but performing processing so as to cut out an outer peripheral surface of the ferrule unit or the like as the light guide path end fixing member inserted into the inside in an axial direction or a radial direction.

(66) FIG. 11 illustrates operation of the dispensing cylinder 12.sub.8 according to the present embodiment. FIGS. 11(a) and 11(b) illustrate suction operation of a minute amount of liquid.

(67) In FIG. 11(a), a distal end surface of the thick shaft portion 12h is located at a lowermost end of the play region 12q as a bottom dead center of the thick shaft portion 12h, that is, the distal end surface of the thick shaft portion 12h is located at a boundary with the small diameter region 12c. Therefore, the thin shaft portion 12f is inserted into the small diameter region 12c. In this state, distal ends of the dispensing tips 211 and 212 attached to the nozzle 11 are inserted into a container storing liquid.

(68) If a stroke of the thick shaft portion 12h (or plunger 12a) is represented by D, a distance from a bottom dead center of a distal end surface of the thick shaft portion 12h (or plunger 12a) in the axial direction is represented by d, and the length of the seal member (member for sealing gas) of the thin shaft portion 12f in the axial direction is represented by d3, the length d0 of the play region 12q in the axial direction is equal to or larger than the sum of the length d1 from a distal end surface of the thick shaft portion 12h to a sealing position of the seal member in the axial direction and the length d3. As described above, 0≤d≤D, d3<d2, and d3<D are satisfied if the length of the small diameter region 12c including the inside of the lower end portion 12d is represented by d2. Note that the cavity 12r at a lower end of the cylinder 12b is a portion to which the lower end portion 12d is attached by screwing.

(69) In FIG. 11(b), when the plunger 12a is raised by a distance d (<d3) from the bottom dead center, the thin shaft portion 12f slides in the small diameter region 12c and rises by the distance d. The thick shaft portion 12h moves with a play in the play region 12q by the distance d. For this reason, a vacuum portion is not generated by movement of the thick shaft portion 12h. Therefore, a large load is not applied to the plunger 12a, and liquid smoothly flows into the dispensing tips 211 and 212 attached to the nozzle 11 in an amount corresponding to S2×d (S2 represents the cross-sectional area of the small diameter region).

(70) Here, d<d3 in FIGS. 11(a) and 11(b) corresponds to a minute amount suction/discharge section.

(71) In FIG. 11(c), when the plunger 12a is moved from the bottom dead center by a distance d=d3, the thin shaft portion 12f is withdrawn from the small diameter region 12c, the thick shaft portion 12h enters the large diameter region 12p, and suction of gas passing through the distal end opening 11a of the nozzle 11 into the play region 12q and the large diameter region 12p starts.

(72) In FIG. 11(d), when the plunger 12a is moved from the bottom dead center by a distance d (=D>d3), the thin shaft portion 12f moves with a play in the play region 12q, the thick shaft portion 12h slides in the large diameter region 12p, and liquid is sucked into the dispensing tip attached to the nozzle 11 in an amount of S1×(D−d0) (S1 represents the cross-sectional area of the large diameter region perpendicular to the axial direction).

(73) d>d0>d3 in FIGS. 11(c) and 11(d) corresponds to a large amount suction/discharge section.

(74) FIG. 12 is a view for explaining operation of the photometric dispensing nozzle units 10.sub.1 to 10.sub.n.

(75) FIG. 12(a) illustrates a state of the photometric dispensing nozzle unit 10.sub.8 in a case where the minute amount dispensing tip 212.sub.8 is attached to the distal end portion 11q of the nozzle 11, and suction/discharge of a minute amount of liquid such as a reagent is performed to the liquid storing unit 27.sub.8 of the container group 20.sub.8. In the dispensing cylinder 12.sub.8, the plunger 12a is located in the minute amount suction/discharge section such that the thin shaft portion 12f slides in the small diameter region 12c.

(76) FIG. 12(b) illustrates a state of the photometric dispensing nozzle unit 10.sub.8 in a case where the large amount dispensing tip 211.sub.8 is attached to the distal end portion 11q of the nozzle 11, and suction/discharge of a large amount of liquid such as a reagent is performed to the liquid storing unit 27.sub.8 of the container group 20.sub.8. In the dispensing cylinder 12.sub.8, the plunger 12a is located in the large amount suction/discharge section such that the thick shaft portion 12h slides in the large diameter region 12p.

(77) FIG. 12(c) illustrates that a dispensing tip is removed from the distal end portion 11q of the nozzle 11.sub.8 using the tip removing member 59a, then the nozzle distal end portion 11q is connected to an opening of the reaction container 238 or connected thereto through a sealing lid, and an optical state in the reaction container is detected.

(78) FIG. 13 illustrates that, in the photometric dispensing nozzle unit 10.sub.8, the dispensing cylinder 120 for large amount suction/discharge can be used instead of the dispensing cylinder 12 while the nozzle 11 is as it is with respect to the flow path built-in support block 76. That is, in accordance with a purpose of a test, it is possible to exchange only the dispensing cylinder for an optimal one while the nozzle 11 is as it is. The dispensing cylinder 120 includes: a cylinder 120b having a cavity (120r, 120p) therein; a lower end portion 12d (see FIG. 10) located at a lower end of the cylinder 120b, having a cylinder lateral hole 120e as a gas suction/discharge port, and attaching the dispensing cylinder 120.sub.8 to the flow path built-in support block 76 by being inserted into the cylinder attachment longitudinal hole 75.sub.8 from a lower side of the flow path built-in support block 76 and screwing with the cylinder 120b inserted from an upper side of the cylinder attachment longitudinal hole 75.sub.8; and a plunger 120a provided so as to be slidable in the cavity (120r, 120p) in the axial direction, located outside the cylinder 120b, and having a flange 120t engaged with the suction/discharge driving member 53d (see FIG. 9) driven by a stepping motor or the like.

(79) The cavity (120r, 120p) formed in the cylinder 120b is a large diameter region 120p having a large diameter inner peripheral surface and a cavity 120r into which the lower end portion 12d is inserted to be attached (see FIG. 10).

(80) The plunger 120a has a thick shaft portion 120h provided so as to be slidable in the large diameter region 120p of the cylinder 120b through an opening 120u provided at the other end of the cylinder 120b. Note that a reference numeral 120k represents a seal member provided in a peripheral direction on an outer peripheral surface of the thick shaft portion 120h.

(81) The dispensing cylinder 120 includes a coiled spring (not illustrated) having one end attached to an annular groove 1201 bored in an upper end surface of the large diameter region 120p, and having the other end wound around the plunger 120a so as to stretch the thick shaft portion 120h. The thick shaft portion 120h is pressed against a step at a boundary with the cavity 120r which is a bottom dead center. The step protrudes in an inward direction toward the lower direction. FIGS. 13(a) and 13(b) illustrate a state in which the plunger 120a is raised, and the thick shaft portion 120h slides with the large diameter region 120p. Note that FIG. 13(a) illustrates the outer shape of the dispensing cylinder 120, which is similar to the outer shape of the dispensing cylinder 12.

(82) Subsequently, regarding operation of the photometric dispensing apparatus 100 according to the present example, a series of treatment operations until real-time PCR of a nucleic acid of a specimen containing bacteria and light measurement thereof are performed will be described below.

(83) In step S1, on the stage 20, the cartridge containers 205 and 206 storing specimens to be tested, the cartridge container 207 capable of storing residual liquid, the cartridge container 201.sub.1 storing various tips, the cartridge container 202.sub.1 in which various cleaning liquids for extracting a nucleic acid and various reagents are prepacked, the cartridge container 203.sub.1 in which a nucleic acid amplification reagent is prepacked, and the cartridge container 204.sub.i having a PCR tube for amplifying a nucleic acid as the reaction container 23.sub.i and storing the sealing lid 25 are loaded. In addition, the eight sets of photometric dispensing nozzle units 10.sub.i are attached to the flow path built-in support block 76.

(84) In step S2, by touching a touch panel or the like as the operation panel 65, an instruction to start a separation/extraction treatment and an amplification treatment is made.

(85) In step S3, an extraction control unit 62 provided in the CPU+program+memory 60 as the photometric dispensing control unit of the photometric dispensing apparatus 100 instructs the nozzle head moving mechanism 51 to move the nozzle head 50 in the Y-axis direction to locate the nozzle head 50 in a corresponding tip or the like storing unit 21.sub.i of a cartridge container 201.sub.i of each of the container groups 20.sub.i. A piercing tip is attached to the nozzle 11 by the nozzle Z-axis moving mechanism 58. The nozzle head 50 is further moved in the Y-axis direction to locate the piercing tip above the first liquid storing unit of the liquid storing unit group 27.sub.i of the container group, and the nozzle is lowered by the nozzle Z-axis moving mechanism 58 to pierce a film covering an opening of the liquid storing unit. Similarly, the nozzle head 50 is moved in the X-axis direction to sequentially perform piercing also for the other liquid storing units of the liquid storing unit group 27.sub.i and the reaction container group 23.sub.i, and the piercing tip is detached into the tip or the like storing unit 21.sub.i by the tip removing mechanism 59.

(86) In step S4, the nozzle head 50 is again moved in the X-axis direction and moved to a tip or the like storing unit group 21.sub.i. The nozzle 11.sub.i is lowered by the nozzle Z-axis moving mechanism 58, and the large amount dispensing tip 211.sub.1 is attached thereto. Next, the dispensing tip 211.sub.1 is raised by the nozzle Z-axis moving mechanism 58 and then moved along the X-axis by the nozzle head moving mechanism 51 to reach the eighth liquid storing unit 27.sub.i of the liquid storing unit group 27.sub.i, and a predetermined amount of isopropanol is sucked from the liquid storing unit 27.sub.i. The dispensing tip 211.sub.1 is moved again along the X-axis, and dispensing is performed into a solution component (NaCl, SDS solution) stored in each of the third and fifth liquid storing units 27.sub.i and distilled water stored in the sixth liquid storing unit 27.sub.1 in a predetermined amount. As a result, 500 μL of a binding buffer solution (NaCl, SDS, isopropanol), 700 μL of cleaning liquid 1 (NaCl, SDS, isopropanol), and 700 μL of cleaning liquid 2 (water: 50%, isopropanol: 50%) are prepared in the third, fifth, and sixth liquid storing units 27.sub.1 as separation/extraction solutions, respectively. At this time, the minute amount/large amount judgement and instruction means 64 judges that the predetermined amount is a large amount based on the instruction from the extraction control unit 62, and the thick shaft portion 12h is located in the large amount suction/discharge section to slide the large diameter region 12p by a distance D corresponding to the predetermined amount.

(87) In step S5, the dispensing tip 211.sub.1 is moved to a sample tube 261 storing a specimen. Thereafter, the small diameter portion 211.sub.ia of the dispensing tip 211.sub.1 is lowered and inserted thereinto using the nozzle Z-axis moving mechanism 58, and the suction/discharge driving member 53d of the suction/discharge driving unit 53 is raised and lowered. Suction/discharge of a suspension of the specimen stored in the sample tube 26.sub.i is thereby repeated to make the specimen suspended in the liquid. Thereafter, the specimen suspension is sucked into the dispensing tip 211.sub.1. The specimen suspension is moved to the first liquid storing unit of the liquid storing unit group 27.sub.1 storing Lysis 1 (enzyme) as a separation/extraction solution along the X-axis by the nozzle head moving mechanism 51. The small diameter portion 211.sub.ia of the dispensing tip 211.sub.i is inserted thereinto through a hole of a pierced film, and suction/discharge is repeated in order to stir the specimen suspension and the Lysis 1.

(88) In step S6, the whole amount of the stirred liquid is sucked by the dispensing tip 211.sub.1 to be stored in the reaction container 23.sub.i including a reaction tube held in the storing hole set at 12° C. by a temperature controller 29, and is incubated. As a result, a protein contained in the specimen is destroyed to reduce the molecular weight thereof. After a lapse of a predetermined time, the dispensing tip 211.sub.i is moved to the second liquid storing unit 27.sub.i of the liquid storing unit 27.sub.i by the nozzle head moving mechanism 51 while the reaction solution is left in the reaction tube. The whole amount of the liquid stored in the second liquid storing unit 27.sub.i is sucked using the nozzle Z-axis moving mechanism 58 and the suction/discharge driving unit 53, and transferred by the nozzle head moving mechanism 51 using the dispensing tip 211.sub.1. The small diameter portion is inserted into the third liquid storing unit 27.sub.i through the hole of the film to discharge the reaction solution.

(89) In step S7, a binding buffer solution as a separation/extraction solution stored in the third liquid storing unit 27.sub.i and the reaction solution are stirred to further dehydrate a solubilized protein, and a nucleic acid or a fragment thereof is dispersed in the solution.

(90) In step S8, the small diameter portion of the dispensing tip 211.sub.i is inserted into the third liquid storing unit 27.sub.i through a hole of the film using the dispensing tip 211.sub.i, and the whole amount is sucked. The dispensing tip 211.sub.i is raised by the nozzle Z-axis moving mechanism 58. The reaction solution is transferred to the fourth liquid storing unit 27.sub.i. A magnetic particle suspension stored in the fourth liquid storing unit 27.sub.i and the reaction solution are stirred. A cation structure in which a Na.sup.+ ion is bonded to a hydroxy group formed on surfaces of magnetic particles contained in the magnetic particle suspension is formed. Therefore, negatively charged DNA is captured by the magnetic particles.

(91) In step S9, by making a magnet 571 of the magnetic force unit 57 approach the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i, the magnetic particles are adsorbed by an inner wall of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i. In a state where the magnetic particles are adsorbed by the inner wall of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i, the dispensing tip 211.sub.i is raised by the nozzle Z-axis moving mechanism 58. The dispensing tip 211.sub.i is moved from the fourth liquid storing unit 27.sub.i to the fifth liquid storing unit 27.sub.i using the nozzle head moving mechanism 51, and the small diameter portion 211.sub.ia is inserted thereinto through a hole of the film.

(92) In a state where a magnetic force to an inside of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i is removed by separating the magnet 571 of the magnetic force unit 57 from the small diameter portion 211.sub.ia, a cleaning liquid 1 (NaCl, SDS, isopropanol) stored in the fifth liquid storing unit 27i is repeatedly sucked and discharged. The magnetic particles are thereby detached from the inner wall and stirred in the cleaning liquid 1, and a protein is thereby cleaned. Thereafter, in a state where the magnetic particles are adsorbed by the inner wall of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i by making the magnet 571 of the magnetic force unit 57 again approach the small diameter portion 211.sub.ia, the dispensing tip 211.sub.i is moved from the fifth liquid storing unit 27.sub.i to the sixth liquid storing unit 27.sub.i by the nozzle head moving mechanism 51.

(93) In step S10, the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i is inserted through a hole of the film using the nozzle Z-axis moving mechanism 58. In a state where a magnetic force to an inside of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i is removed by separating the magnet 571 of the magnetic force unit 57 from the small diameter portion 211.sub.ia, a cleaning liquid 2 (isopropanol) stored in the sixth liquid storing unit 27.sub.i is repeatedly sucked and discharged. The magnetic particles are thereby stirred in the liquid, NaCl and SDS are removed, and a protein is cleaned. Thereafter, in a state where the magnetic particles are adsorbed by the inner wall of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i by making the magnet 571 of the magnetic force unit 57 again approach the small diameter portion 211.sub.ia, the dispensing tip 211.sub.1 is raised by the nozzle Z-axis moving mechanism 58, and then moved from the sixth liquid storing unit 27.sub.i to the seventh liquid storing unit 27.sub.i storing distilled water by the nozzle head moving mechanism 51.

(94) In step S11, the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i is lowered by the nozzle Z-axis moving mechanism 58 through the hole. By repeating suction/discharge of the distilled water at a slow flow rate in a state where the magnetic force is applied to an inside of the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i, the cleaning liquid 2 (isopropanol) is replaced with the water and removed. Thereafter, by sucking and discharging the magnetic particles repeatedly in distilled water as the dissociated solution in a state where the magnet 571 of the magnetic force unit 57 is separated from the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i and the magnetic force is removed, stirring is performed, and a nucleic acid retained by the magnetic particles or a fragment thereof is dissociated (eluted) from the magnetic particles into the liquid. Thereafter, by making the magnet 571 approach the small diameter portion 211.sub.ia of the dispensing tip 211.sub.i, a magnetic field is applied to an inside of the small diameter portion, the magnetic particles are adsorbed by the inner wall, and the solution containing the extracted nucleic acid or the like is left in the eighth liquid storing unit. The dispensing tip 211.sub.i is moved to the storing unit in which the dispensing tip 211.sub.i of the tip or the like storing unit group 21.sub.i was stored by the nozzle head moving mechanism 51. The dispensing tip 211.sub.i which has adsorbed the magnetic particles from the nozzle 11.sub.i is detached into the storing unit together with the magnetic particles using the removing member 591 of the tip removing mechanism 59.

(95) Subsequent steps S12 to S15 correspond to a nucleic acid amplification step.

(96) In step S12, based on the instruction from the nucleic acid amplification control unit 63, according to the instruction from the minute amount/large amount judgement and instruction means 64, a new minute amount dispensing tip 212.sub.i is attached to the nozzle 11.sub.i using the nozzle head moving mechanism 51 and the nozzle Z-axis moving mechanism 58. A minute amount of the solution containing a nucleic acid or the like stored in the eighth liquid storing unit 27.sub.i is sucked, transferred to a PCR tube as the reaction container 23±storing an amplification solution in advance, discharged, and introduced into the container.

(97) In step S13, the minute amount dispensing tip 212i attached to the nozzle 11.sub.i by the nozzle head moving mechanism 51, the nozzle Z-axis moving mechanism 58, and the tip removing mechanism 58 is detached into the tip or the like storing unit 21.sub.i. The nozzle head 50 is moved by the nozzle head moving mechanism 51, and the nozzle 11.sub.i is moved to an upper portion of the sealing lid storing unit as the tip or the like storing unit 21.sub.i storing the sealing lid 25.sub.i of the container group 20. By lowering the nozzle 11.sub.i using the nozzle Z-axis moving mechanism 58, a depression 258.sub.i on an upper side of the sealing lid 25.sub.i is fitted to the distal end portion 11q of the nozzle 11.sub.i and attached thereto. After raising the nozzle 11.sub.i by the nozzle Z-axis moving mechanism 58, the sealing lid 25.sub.i is located on the PCR tube (23.sub.i) using the nozzle head moving mechanism 51. The sealing lid 25.sub.i is lowered by the nozzle Z-axis moving mechanism 58, fitted to an opening of the PCR tube 231.sub.i, and is attached and sealed.

(98) In step S14, the photometric control unit 61 instructs the nozzle head moving mechanism 51 to move the nozzle head 50 along the X-axis, thereby locates the nozzle 11.sub.i above the PCR tube (23.sub.i) to which the sealing lid 25.sub.i is attached, and lowers the nozzle 11.sub.i by the Z-axis moving mechanism 58. As a result, the distal end portion 11q of the nozzle 11 is attached to the inside of the depression of the sealing lid 25.sub.i, and the lower end portion 11q of the nozzle 11 is brought into contact or close contact with the bottom of the depression.

(99) At this time, in step S15, the nucleic acid amplification control unit 63 instructs the temperature controller 29 to repeat a temperature control cycle by real time PCR, for example, a cycle of heating the PCR tube (23.sub.i) at 96° C. for five seconds and heating the PCR tube (23.sub.i) at 60° C. for 15 seconds, for example, 49 times.

(100) In step S16, when temperature control in each cycle is started by the nucleic acid amplification control unit 63, the photometric control unit 61 determines start of an extension reaction step in each cycle, and instructs each measurement end 44j of the measuring device 40 to move the connection end array 30 continuously or intermittently. The moving speed is calculated based on stable light receivable time, a fluorescence lifetime, the number of the container groups 20.sub.i (eight in this example), and the like. As a result, light reception from the eight PCR tubes (23.sub.i) in total within the stable light receivable time is completed. Here, the “stable light receivable time” is time during which a light receivable optical state in the reaction container is stably maintained. For example, in a case of a TaqMan probe in an intercalation method of real-time PCR, a LUX method, or a hybridization method, time during which an extension reaction of each cycle of PCR is performed corresponds thereto. Note that in a case where a FRET probe is used in the hybridization method, time during which annealing is performed corresponds thereto.

(101) In step S17, the photometric control unit 61 determines, for example, the timing of optical connection between the optical fiber (bundle) 31.sub.i of the nozzle 11.sub.i and each of a first measurement end (irradiation port of excitation light) of the measurement end 44 and a second measurement end (emission port of emitted light) thereof, and instructs the measuring device 40 to receive light.

(102) This measurement is performed on a cycle in which exponential amplification is performed, and an amplification curve is obtained based on the measurement. Various analyses are performed based on the amplification curve. Note that at the time of measurement, the photometric control unit 61 can heat a heater provided in each container group 20.sub.i to prevent dew condensation of the sealing lid 25 and can perform clear measurement.

(103) FIG. 14 illustrates an experimental example illustrating performance of the photometric dispensing apparatus according to the present embodiment. This experiment was performed at a room temperature of 20.9° C. and a humidity of 31%. Using the present photometric dispensing apparatus 100, 10 μL, 20 μL, and 25 μL of distilled water were sucked by an already weighed tube. The suction amount in a case of performing dispensing into another container of 1.5 mL volume was determined as a difference between the weight of the already weighed tube before dispensing and the weight of the already weighed tube after suction, measured using the eight photometric dispensing nozzle units for five solutions. A difference between a maximum value and a minimum value (max−min), an average, a deviation (SD), a 6-fold deviation (6SD), a coefficient of variation, and accuracy for the results were measured. As a result, it was indicated that the coefficient of variation of the present photometric dispensing apparatus was sufficiently smaller than those of other dispensing apparatuses of the present applicant (for example, 10% or less for 10 μL, 3% or less for 25 μL, 1.5% or less for 200 μL), and that reliability for dispensing was high.

(104) FIG. 15 illustrates results of measurement of an average value (AVE), a maximum value (MAX), a minimum value (MIN), a deviation (SD), and a coefficient of variation (CV) in a case where eight fluorescence solutions (each having a volume of 20 μl) of the same fluorescence (FITC yellow green) was irradiated with excitation light (Ch0) using the photometric dispensing nozzle unit 11i (i=1 to 8) of the photometric dispensing apparatus 100, and an emission amount (AD conversion value) was repeatedly measured five times, and indicates that the coefficient of variation was small and reliability was high. Moreover, a coefficient of variation or the like was simultaneously measured also for the dispensing amount for each lane.

(105) FIG. 16 illustrates results of measuring fluorescence for 20 μL of fluorescence solutions obtained by diluting fluorescence (FITC yellowish green) solutions stored in prepared two containers so as to have three concentrations (0.1, 0.05, 0.025) using six sets (lanes 1 to 6) of the photometric dispensing nozzle units of the photometric dispensing apparatus 100 (lanes 1 to 3.fwdarw.operation 1, lanes 4 to 6.fwdarw.operation 2). The measured results are illustrated as a table (a) of a peak value of fluorescence (digital value obtained by the photoelectric conversion unit), raw data (b) obtained by measurement with the measuring device 40 (obtained as a time change with movement of the connection end array 30), and a calibration curve (c) created. These measurement results indicate that a fluorescence amount according to a concentration can be obtained with high accuracy.

(106) The above-described embodiments have been described specifically for the purpose of better understanding of the present invention, and do not limit another embodiment. Therefore, the above-described embodiments can be modified within a range not changing the gist of the invention. For example, as an example of the photometric dispensing nozzle unit, only the dispensing cylinder 12 according to the first embodiment has been described for the photometric dispensing apparatus and the method thereof. However, needless to say, the dispensing cylinder 120 according to the second embodiment can be used. The numerical values, the numbers of times, the shapes, the numbers of items (for example, the number of sets of the photometric dispensing nozzle units used in the photometric dispensing apparatus is not limited to eight, and may be larger or smaller), the amounts, and the like used in the above description are not limited to these cases. As an example of the light guide end portion of the photometric dispensing nozzle unit, only the case of providing both the irradiation end and the light receiving end in the nozzle unit has been described. However, only one of the irradiation end and the light receiving end may be provided. In this case, the other of the irradiation end and the light receiving end is provided at a position which is outside the photometric dispensing nozzle unit and/or outside the dispensing tip attached to the nozzle, and to an upper portion of which a distal end opening of the nozzle or an opening of the dispensing tip can be located, for example, on a stage. Furthermore, the other is provided under a transparent bottom of the container placed on the stage. In a case where a dispensing tip is attached to the nozzle, both the irradiation end and the light receiving end are preferably provided in a positionable manner so as to be located on a vertical common axis commonly passing through the opening of the dispensing tip attached to the nozzle and the attachment opening.

INDUSTRIAL APPLICABILITY

(107) The present invention relates to a photometric dispensing nozzle unit, a photometric dispensing apparatus, and a photometric dispensing method, performs a test of a specimen collected from a patient or the like, optical measurement thereof, and recording thereof, and can be used particularly in a field requiring handling of a biopolymer and a low molecular biological substance such as a gene, an immune system, an amino acid, a protein, or a sugar, for example, in a biochemistry field, an industrial field, an agriculture field such as food, agriculture, or fishery processing, a pharmaceutical field, and a medical field such as hygiene, health, immunity, diseases, or genetics.

REFERENCE SIGNS LIST

(108) 10.sub.1 to 10.sub.n (n=1, . . . 8, . . . ) Photometric dispensing nozzle unit 11.sub.1 to 11.sub.n (n=1, . . . 8, . . . ) Nozzle 12.sub.1 to 12.sub.n (n=1, . . . 8, . . . ) Dispensing cylinder 13.sub.1 to 13.sub.n (n=1, . . . 8, . . . ) Pressure sensor 20 Stage 20.sub.1 to 20.sub.n (n=1, . . . 8, . . . ) Container group 29 Temperature controller 40 Light measuring device 50 Nozzle head 51 Nozzle head moving mechanism 53 Suction/discharge driving unit 57 Magnetic force unit 58 Nozzle Z-axis moving mechanism 59 Tip removing mechanism 60 CPU+program+memory (photometric dispensing control unit) 70 Flow path built-in support body 71.sub.1 to 71.sub.n (n=1, . . . 8, . . . ) Connecting flow path (suction/discharge flow path) 72.sub.1 to 72.sub.n (n=1, . . . 8, . . . ) Pressure sensor flow path 100 Photometric dispensing apparatus