U.S. patent application number 11/521339 was filed with the patent office on 2007-01-11 for dispenser operation verification apparatus and verification method.
This patent application is currently assigned to Precision System Science Co., Ltd.. Invention is credited to Claus Bamberg, Volker Degenhardt, Hermann Leying, Kimimichi Obata, Hideji Tajima.
Application Number | 20070009392 11/521339 |
Document ID | / |
Family ID | 18500229 |
Filed Date | 2007-01-11 |
United States Patent
Application |
20070009392 |
Kind Code |
A1 |
Tajima; Hideji ; et
al. |
January 11, 2007 |
Dispenser operation verification apparatus and verification
method
Abstract
An object is to provide a dispenser operation verification
apparatus and verification method that enables operation with high
reliability and high accuracy. The construction is such that with a
dispenser comprising: one or a plurality of transparent or
semi-transparent liquid passages capable of liquid suction,
discharge and storage; a pressure control device for controlling
the pressure in the liquid passage; a transport device for
effecting relative movement between a container and the liquid
passage; and an operation instruction device for issuing operating
instructions to the pressure control device and the transport
device, the operation of the dispenser is verified by providing; a
detecting device for detecting an optical condition of the liquid
passage, a movable region thereof or a part of that region, and a
judgement device for judging the result of the instruction related
to the liquid passage issued by the operation instruction device,
based on the optical conditions detected by the detecting
device.
Inventors: |
Tajima; Hideji;
(Matsudo-shi, JP) ; Obata; Kimimichi;
(Matsudo-shi, JP) ; Leying; Hermann; (Matsudo-shi,
JP) ; Bamberg; Claus; (Mannheim, DE) ;
Degenhardt; Volker; (Mannheim, DE) |
Correspondence
Address: |
HAYNES AND BOONE, LLP
901 MAIN STREET, SUITE 3100
DALLAS
TX
75202
US
|
Assignee: |
Precision System Science Co.,
Ltd.
Matsudo-shi
JP
Roche Diagnostics GmbH
Mannheim
DE
|
Family ID: |
18500229 |
Appl. No.: |
11/521339 |
Filed: |
September 14, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10169474 |
Sep 17, 2002 |
|
|
|
PCT/JP00/09335 |
Dec 27, 2000 |
|
|
|
11521339 |
Sep 14, 2006 |
|
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|
Current U.S.
Class: |
422/400 ;
422/63 |
Current CPC
Class: |
G01N 2035/1018 20130101;
G01N 35/1011 20130101; G01N 2035/1013 20130101; G01N 35/1016
20130101 |
Class at
Publication: |
422/100 ;
422/063 |
International
Class: |
B01L 3/02 20060101
B01L003/02 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 28, 1999 |
JP |
11-372308 |
Claims
1. A dispenser operation verification method, wherein a dispenser
comprising: one or a plurality of transparent or semi-transparent
liquid passages capable of liquid suction, discharge and storage;
pressure control means for controlling the pressure in the liquid
passage; transport means for effecting relative movement between a
container and the liquid passage; and operation instruction means
for issuing operating instructions to said pressure control means
and said transport means, is used and verification of the operation
of the dispenser is effected by having; an operating step for
performing operations related to said liquid passage, a detection
step for detecting an optical condition of said liquid passage a
movable region thereof or a part of that region, and a judgement
step for judging the result of the instruction related to an
operation of agitation by sucking and discharging the liquid into
or from the liquid passage respectively issued by said operation
instruction means, based on the optical conditions of the contents
of the liquid passage detected by said detection step and
instructing to the operation instruction means based on the result
of the judgement.
2. A dispenser operation verification method according to claim 1,
wherein said judgement step judges the result of the instruction,
based on information besides said optical condition, selected from
amongst information containing; operation information related to
the operation instructions of said operation instruction means,
object information related to objects which said dispenser draws
in, discharges and stores, and device information related to said
dispenser including the liquid passage.
3. A dispenser operation verification method according to claim 2,
wherein said operation information contains: suction amount or
discharge amount; presence of suction or discharge; speed of
suction or discharge; suction and discharge operation including
time of suction or discharge; and/or information on movement
operation including movement path, movement direction and/or
movement distance, said object information contains the kind or
nature of liquid and/or the type and/or the presence of suspensions
such as magnetic particles and the like, and said device
information contains the nature and shape of the liquid passage
and/or information showing the relationship between the distance
from a suction aperture and the capacity of said liquid
passage.
4. A dispenser operation verification method according to claim 1,
wherein said detection step has a step for receiving light at one
or a plurality of locations, from said liquid passage, said movable
region or a part of the region.
5. A dispenser operation verification method according to claim 4,
wherein in the case where said liquid passage is capable of upward
and downward movement, and in the case where said light receiving
means is fixedly provided outside of the upward and downward
movement path of said liquid passage such that an optical axis
thereof is directed toward a predetermined height location of the
upward and downward movement path, said detecting step detects the
lower edge of the liquid passage and up to the upper level to where
the liquid can be stored while performing the upward and downward
movement by said transport means.
6. A dispenser operation verification method according to claim 1,
wherein said detection step is performed by receiving light emitted
toward said liquid passage, the movable region or a part of the
regions.
7. A dispenser operation verification method according to claim 1,
wherein said detecting step is performed by picking up an image of
said liquid passage, a movable region thereof or a part of the
region.
8. A dispenser operation verification method according to claim 1,
wherein said detecting step receives light spanning the maximum
width of the upward and downward movement path so that the light
from the maximum width of one or a plurality of the upward and
downward movement paths of said liquid passage can be received or
picked up.
9. A dispenser operation verification method according to claim 1,
wherein said detecting step shines light on the maximum width of
one or a plurality of the upward and downward movement paths of
said liquid passage.
10. A dispenser operation verification method according to claim 1,
wherein said judgement step judges whether or not conditions
related to the liquid passage corresponds to the instruction
result, by analyzing the optical pattern composed of: the light
amount, the light intensity or the image; temporal fluctuations of
the light amount, the light intensity or the image; or the spatial
distribution of the light amount, the light intensity or the image,
detected by said detecting step.
11. A dispenser operation verification method according to claim
10, wherein conditions related to the condition of the liquid
passage includes, the concentration of air bubbles or a suspension
such as a magnetic particles in the liquid passage, the degree of
suspension or mixing of the liquid in the liquid passage, or a
reaction condition such as light emission.
12. A dispenser operation verification method according to claim 6,
wherein said judgment step judges, in the case of a light emitting
level where the amount or intensity of the light received in said
detecting step is almost the same as the amount or intensity of the
light from light emission, that there is no liquid passage present,
and in the case of a predetermined shielding level where the amount
or intensity of the light received in said detecting step is
smaller than the amount or intensity of the light from said light
emission, that a liquid passage is present.
13. A dispenser operation verification method according to claim 1,
wherein said judgment step judges, based on a time difference
between a time that said pressure control means is instructed to
draw in a suction amount of liquid up to a predetermined height of
said liquid passage and a time that the amount or intensity of the
light detected in said detecting step actually changes, a condition
of liquid flow resistance or a condition of blockage by foreign
matter in said liquid passage.
14. A dispenser operation verification method according to claim
10, wherein said judgement step, after detecting the liquid surface
by said detection step, judges the condition of the liquid during
the operation of suction into or discharge from the liquid passage,
by analyzing a suction and discharge operation by pressure control
means, as well as an optical pattern composed of the light amount,
the light intensity or the image; temporal fluctuations of the
light amount, the light intensity or the image; or spatial
distribution of the light amount, the light intensity, or the
image, detected in said detecting step.
15. A dispenser operation verification method according to claim 1,
wherein said judgement step, in the condition where the liquid is
drawn up to lower than a predetermined height in said liquid
passage, by raising said liquid passage or lowering said detecting
means, judges the size of the volume drawn into said liquid
passage, based on the distance moved to where the liquid surface in
said liquid passage crosses the detecting location of said
detecting means, and information showing the relationship between a
predetermined optional distance from said suction aperture and the
capacity of said liquid passage.
16. A dispenser operation verification method according to claim 1,
wherein said judgement step, in the condition where the liquid is
drawn into said liquid passage, by raising said liquid passage or
lowering said detecting means, detects the liquid surface twice
before it reaches the tip of the liquid passage, and also in the
condition where the liquid is drawn up to a higher level than said
predetermined height, by raising said liquid passage or lowering
said detecting means, judges a liquid shortage in the case where a
change is detected from a condition with liquid present to a
condition with liquid again absent.
17. A dispenser operation verification method according to claim 1,
wherein said dispenser also has magnetic means outside of said
liquid passage capable of applying and removing a magnetic field to
and from each liquid passage, and said operation instruction means
also instructs said magnetic means to apply and remove a magnetic
field, and said judgement step also judges the instruction result
made by said magnetic field in relation to the liquid passage.
18. A dispenser operation verification method according to claim 1,
wherein said liquid passage is a pipette tip detachably mounted on
a nozzle provided on the dispenser, and said dispenser has a
detaching device for the pipette tip, and said operation
instruction means also gives said transport means and said
detaching device an instruction to attach and detach the pipette
tip, and said judgement step judges the result of the instruction
of attaching and the pipette tip.
19. A dispenser operation verification method according to claim 1,
further comprises a step of adding a coloring matter having the
absorption maximum nearby the wave length of the light from an
emission means or an optical source or a suspension agent capable
of dispersing insoluble solid substance with the liquid for aiding
in or capable of detection, to the liquid being sucked, discharged
or stored in the liquid passage before the detection step.
Description
CROSS REFERENCE
[0001] This application is a divisional of copending application
Ser. No. 10/169,474, filed Jun. 28, 2002 (35 U.S.C 371 Filing Date
Sep. 17, 2002), which is a national phase filing of international
application No. PCT/JP00/09335, filed Dec. 27, 2000, which claims
priority to Japanese patent application No. 11-372308, filed Dec.
28, 1999.
TECHNICAL FIELD
[0002] The present invention relates to a dispenser operation
verification apparatus and verification method, and more
specifically relates to an operation verification apparatus and
operation verification method for a dispenser provided with one or
a plurality of transparent or semi-transparent liquid passages
capable of the suction, discharge and storage of liquid
[0003] The present invention is for performing high accuracy
operations or processes with high quantification using a dispenser
in various fields such as those fields which require the treatment
of minuscule amounts of liquid, for example, the engineering field;
the medical fields of hygiene, health, immunity, disease, genetics
and the like; the agricultural science fields of food, agricultural
products, marine products processing and the like; the science
fields of biology, chemistry and the like; the pharmaceutical field
and the like. The dispenser is for performing various operations
and processes regarding liquids such as reagents or the like using
a pipette tip or a nozzle. The working or operation of the
dispenser include not only the suction and discharge of liquid, but
also storage, agitation, transfer, separation, suspension, mixing
and purification.
BACKGROUND ART
[0004] Heretofore, verifying whether the operation result or
working result of a dispenser corresponds to the instruction of the
user or not is performed by eye, using graduations or the like
attached to a pipette tip or the like, or at most only by
measurement of the air pressure in a pipette tip by a pressure
sensor installed in the dispenser to detect lack of suction, liquid
level and tip blockage.
[0005] Furthermore, in the case where a process is carried out by
automated equipment that performs a series of operations
sequentially and automatically, after the series of operations
finishes, the verification has been done by no more than measuring
the final liquid amount or the like obtained, and the operation has
not been verified at each step during the process nor
automatically.
PROBLEMS TO BE SOLVED BY THE INVENTION
[0006] Accordingly, there are problems that examination by eye is a
big burden on the user, and also verifying whether the amount of
suction, the amount of discharge or the like is correct or not
cannot be performed accurately by eye.
[0007] Furthermore, there is another problem in that since
measurement by a pressure sensor requires an air gap in the pipette
tip, even if trying to perform a minuscule, quantified amount of
dispensing (1-5 .mu.liter), high accuracy quantification cannot be
ensured. Moreover, there is another problem in that the condition
of the pipette tip cannot be determined adequately or accurately by
measuring only the air pressure in the pipette tip.
[0008] Furthermore, there is another problem in that the structure
of the nozzle becomes complicated because the pressure sensor is
installed so as to contactingly communicate with the pipette
tip.
[0009] Moreover, since it is not easy to verify which malfunction
has occurred, and in which operation, by only measuring the final
liquid amount after a series of operations is finished, especially
in a process that requires the accurate treatment of a minuscule
amount; even a small difference in the liquid amount or the like by
a small malfunction becomes compounded by further operations, and
there is a possibility of obtaining, in the end, an extreme
variance in the amount of liquid or the like from that initially
planned, so that there is a problem in that verifying the operation
needs to be performed automatically at each step.
[0010] Therefore, the present invention is aimed at solving the
above mentioned problems, and a first object is to provide a
dispenser operation verification apparatus and a verification
method that improves the reliability and accuracy of the dispenser
by verifying whether the dispenser is operating as instructed or
not.
[0011] A second object is to provide a dispenser operation
verification apparatus and verification method that can verify the
operation of the dispenser automatically, promptly, efficiently and
accurately, without any human intervention.
[0012] A third object is to provide a dispenser operation
verification apparatus and a verification method which enables the
dispenser to perform high accuracy processes quantitatively, and
accordingly qualitatively, by verifying the operation of the
dispenser, especially when treating genetic materials such as DNA
or the like, bio-polymers of immune substances or the like and
minuscule amounts of bio-compound liquid or the like.
[0013] A fourth object is to provide a dispenser operation
verification apparatus and a verification method that performs
verification of the dispenser operation with high reliability
regarding whole processes consisting of a series of operations, by
performing the operations while verifying the operation of the
dispenser.
[0014] A fifth object is to provide a low-cost dispenser operation
verification apparatus and verification method, which has a simple
construction and can perform easy and reliable verification by
detecting the operation of the dispenser remotely, without needing
to interact directly with the inside of the liquid passage in the
way that a pressure sensor does
DISCLOSURE OF THE INVENTION
[0015] To solve the above problems, a first aspect of the invention
is that, with a dispenser comprising; one or a plurality of
transparent or semi-transparent liquid passages capable of liquid
suction, discharge and storage, a pressure control device for
controlling the pressure in the liquid passage, a transport device
for effecting relative movement between a container and the liquid
passage, and an operation instruction device for issuing operating
instructions to the pressure control device and the transport
device, the operation of the dispenser is verified by providing; a
detecting device for detecting an optical condition of the liquid
passage, a movable region thereof or a part of that region, and a
judgement device for judging the result of the instruction related
to the liquid passage issued by the operation instruction device,
based on the optical conditions detected by the detecting
device.
[0016] Here, the liquid passage corresponds to a nozzle provided on
the dispenser, a tip detachably mounted on the nozzle or both the
nozzle and the tip detachably mounted on the nozzle.
[0017] In the case of "relative movement between a container and
the liquid passage", there are cases where the container moves with
the liquid passage fixed, where the liquid passage moves with the
container fixed, and where both move. To be specific, "the
judgement device" is comprised of a CPU, a memory device, a data
display, a data output device for outputting a signal to another
device, and the like.
[0018] According to the first aspect of the invention, the
dispenser is provided with a detecting device for detecting the
optical condition of the liquid passage, a movable region thereof
or a part of that region, and a judgement device for judging the
result of the instruction related to the liquid passage issued by
the operation instruction device, based on the optical conditions
detected by the detecting device.
[0019] Accordingly, regarding the operation of the dispenser,
highly reliable and accurate verification can be performed at each
operation. Furthermore, the operation of the dispenser can be
verified automatically, promptly and efficiently, without any human
intervention. By verifying the operation of the dispenser according
to the present invention, especially when treating genetic
materials such as DNA or the like, bio-polymers of immunity
substances or the like and minuscule amounts of bio-compound liquid
or the like, high accuracy processes can be performed
quantitatively and, accordingly, qualitatively. Moreover, by
performing the operations while verifying the operation of the
dispenser, verification of the dispenser operation regarding the
overall processing consisting of a series of operations can be
performed with high reliability. Furthermore, the operation of the
dispenser can be easily verified because of its simple structure,
which provides a low cost dispenser operation verification
apparatus and verification method.
[0020] Especially, according to the present invention, since the
condition of the liquid passage is detected and judged optically,
and not judged by the measurement of the pressure in the liquid
passage, it is not necessary to draw air into the liquid passage,
and hence, if the liquid is drawn up to the full capacity of the
liquid passage, extremely high quantification can be obtained.
Furthermore, since the condition is judged optically, various kinds
of operation can be verified.
[0021] A second aspect of the invention is that with the first
aspect of the invention, the judgement device judges the result of
the instruction, based on information besides the optical
condition, selected from amongst information containing; operation
information related to the operation instructions of the operation
instruction device, object information related to objects which the
dispenser draws in, discharges and stores, and device information
related to the dispenser including the liquid passage.
[0022] According to the second aspect of the invention, accurate
and highly reliable verification of various aspects of operation
can be performed, since the judgement device judges the result of
the instruction, based on information besides the optical
condition, selected from amongst information containing, the
operation information, the object information and the device
information.
[0023] A third aspect of the invention is that with the second
aspect of the invention, the operation information contains:
suction amount or discharge amount; presence of suction or
discharge; speed of suction or discharge; suction and discharge
operation including time of suction or discharge; and/or
information on movement operation including movement path, movement
direction and/or movement distance, the object information contains
the kind or nature of liquid and/or the type and/or the presence of
suspensions such as magnetic particles and the like, and the device
information contains the nature and shape of the liquid passage
and/or information showing the relationship between the distance
from a suction aperture and the capacity of the liquid passage.
[0024] According to the third aspect of the invention, for the
contents of various operations, verification of fine operations is
enabled.
[0025] A fourth aspect of the invention is that with the first
aspect of the invention, the detecting device has one or a
plurality of light receiving devices, fixed or movably provided
outside of the liquid passage, a movable region thereof or a part
of the region, so as to have an optical axis directed
theretowards.
[0026] Here, "light receiving device" is a photodiode,
phototransistor, CdS or the like Furthermore, in the case where the
liquid passage is movable, the light receiving device may be fixed.
Moreover, in the case where the liquid passage is fixed and the
container moves, the light receiving device should be movable with
respect to the liquid passage.
[0027] According to the fourth aspect of the invention, by
receiving light at one or a plurality of locations outside of the
liquid passage, from the liquid passage, the movable region and the
like, the optical condition of the liquid passage can be obtained
from various directions, accurately and without contacting the
liquid passage.
[0028] A fifth aspect of the invention is that with the fourth
aspect of the invention, in the case where the liquid passage is
capable of upward and downward movement, the light receiving
devices are fixedly provided outside of the upward and downward
movement path of the liquid passage such that the optical axis
thereof is directed toward a predetermined height location of the
upward and downward movement path.
[0029] Here, "predetermined height location" is for example, a
location through which the lower end of the liquid passage and an
upper level to which liquid can be stored, can be passed through by
the transport device.
[0030] According to the fifth aspect of the invention, since the
light receiving device can be fixed at a predetermined height
location by utilizing the transport device of the liquid passage,
it can be produced with a low cost, and simple construction.
[0031] A sixth aspect of the invention is that with either one of
the fourth aspect of the invention and the fifth aspect of the
invention, the detecting device has one or a plurality of light
emitting devices which are fixed at or can move to a location for
emitting light toward the liquid passage, a movable region thereof,
or part of the region.
[0032] Here, the "light emitting device" is for example, an LED
(light emitting diode), or a neon or tungsten lamp. Furthermore,
the wavelength that the light emitting device emits may be near
infrared light, and in the case of visible light of 600 nm or more,
even with a low concentration of suspension, the light is
transmitted with little attenuation.
[0033] Furthermore, the light emitting devices are provided at the
location where the light receiving devices can detect light. For
example, the location where the light emitting devices opposes the
light receiving devices with the movement path or a part of the
region therebetween, or a location where the light from the light
emitting devices is reflected by the liquid passage and can be
received by the light receiving devices.
[0034] According to the sixth aspect of the invention, by providing
the light emitting device and emitting light therefrom, detection
can be performed reliably and accurately and also, verification of
various fine operations can be conducted depending on the liquid
object.
[0035] A seventh aspect of the invention is that with the first
aspect of the invention, the detecting device has an image pick up
device for picking up images of the liquid passage, the movable
region thereof or a part of the region, which is fixed or movably
provided at a location capable of image pick up outside of the
liquid passage or the movable region thereof. Here, the "image pick
up device" has a one-dimensional or two-dimensional CCD type or MOS
type image sensor.
[0036] According to the seventh aspect of the invention, since by
providing the image pickup device and the linear form light
receiving device, the optical condition of a wide range of the
region can be determined wholly and at once and detected promptly,
detection and judgement can be done efficiently, promptly, and
simply.
[0037] An eighth aspect of the invention is that with either one of
the fourth aspect of the invention and the seventh aspect of the
invention, the light receiving device or the image pick up device
is provided in a line form spanning the maximum width of the
transport path so as to be able to receive or to image pick up
light from the maximum width of two or more of the liquid passages
or the transport path of two or more of the liquid passages.
[0038] In the eighth aspect of the invention, an effect as already
explained for the seventh aspect of the invention is
demonstrated.
[0039] A ninth aspect of the invention is that with the eighth
aspect of the invention, with the detecting device, the light
emitting device spanning the maximum width is provided in linear
form at an opposing location to the light receiving device with the
liquid passage, the movable region thereof or a part of the region
therebetween, such that light can be directed to the maximum width
of two or more of the liquid passages or the transport path of two
or more of the liquid passages.
[0040] In the ninth aspect of the invention, an effect as already
explained for the seventh aspect of the invention is
demonstrated.
[0041] A tenth aspect of the invention is that with the first
aspect of the invention, the judgement device judges whether or not
conditions related to the liquid passage corresponds to the
instruction result, by analyzing the optical pattern composed of:
the light amount, the light intensity or the image; the temporal
fluctuations of the light amount, the light intensity or the image;
or the spatial distribution of the light amount, the light
intensity or the image. Here, "intensity" includes for example,
illumination and brightness, detected by the detecting device
[0042] According to the tenth aspect of the invention, the
judgement device, by analyzing the optical pattern composed of: the
light amount, the light intensity or image; temporal fluctuations
of the light amount, light intensity or image; spatial distribution
of the light amount, the light intensity or image; and the like
detected by the detecting device, the condition related to the
liquid passage can be judged precisely and finely.
[0043] An eleventh aspect of the invention is that with the tenth
aspect of the invention, conditions related to the liquid passage
include, the inaction or action status of the liquid passage, and
physical or chemical inaction or fluctuation conditions of the
contents of the liquid passage; the condition of the liquid passage
includes, the presence of a liquid passage, the location of the
liquid passage, the shape of the liquid passage, and the nature
such as transparency; the physical condition of the contents of the
liquid passage includes, the presence of liquid in the liquid
passage, the presence of the surface or interface of the liquid in
the liquid passage or the location thereof, the amount of the
liquid in the liquid passage; the chemical condition of the
contents in the liquid passage includes, the kind or nature such as
viscosity of the liquid in the liquid passage, air bubbles in the
liquid in the liquid passage or the presence of a suspension such
as magnetic particles or the concentration thereof, the degree of
suspension or mixing of the liquid in the liquid passage, or a
reaction condition such as light emission.
[0044] The present invention also enables the verification of
liquid suction and discharge, the presence of storage and/or
agitation, the presence of separation by a magnetic device or the
like, suction amount, discharge amount, storage amount, liquid
condition (presence of suspension, mixing, reaction, flocculent, or
precipitation, clarity, translucence, density, concentration,
dilution, color and the like), and the like.
[0045] According to the eleventh aspect of the invention, since
various kinds of condition related to the liquid passage can be
judged, precise and detailed information can be obtained with a
simple construction.
[0046] A twelfth aspect of the invention is that with either one of
the sixth aspect of the invention and the ninth aspect of the
invention, the judgment device judges, in the case of a light
emitting level where the amount or intensity of the light received
by the light receiving device is almost the same as the amount or
intensity of the light from the light emitting device, that there
is no liquid passage present, and in the case of a predetermined
shielding level where the amount or intensity of the light received
by the light receiving device is smaller than the amount or
intensity of the light from the light emitting device, that a
liquid passage is present.
[0047] According to the twelfth aspect of the invention, by simple
analysis, the presence of the liquid passage can be judged with
accuracy and high reliability.
[0048] A thirteenth aspect of the invention is that with the tenth
aspect of the invention, the judgement device judges, based on a
time difference between a time that the pressure control device is
instructed to draw in a suction amount of liquid up to the height
of the liquid passage and a time that the amount or intensity of
the light detected by the detecting device actually changes, a
condition of liquid flow resistance or a condition of blockage by
foreign matter in the liquid passage.
[0049] According to the thirteenth aspect of the invention, because
of the simple construction and analysis, various kinds of
conditions can be judged.
[0050] A fourteenth aspect of the invention is that with the tenth
aspect of the invention, the judgement device, after detecting the
liquid surface, judges the condition of the liquid during the
operation of suction into or discharge from the liquid passage, by
analyzing the suction and discharge operation by a pressure control
device, as well as the optical pattern composed of: the light
amount, the light intensity or the image; temporal fluctuations of
the light amount, the light intensity or the image; or spatial
distribution of the light amount, the light intensity, or the
image, detected by the detecting device.
[0051] Here, to detect the presence of liquid in the liquid
passage, with the fourteenth aspect of the invention, the judgement
device, in the case where the amount or intensity of the light
received by the light receiving device is greater than the
predetermined shielding level, but less than the light emitting
level, and the transmissivity of the liquid to be drawn up is
higher than in the liquid passage, judges that the liquid exists in
the liquid passage. Moreover, the judgement device, in the case
where the amount or intensity of the light received by the light
receiving device is less than the predetermined shielding level,
and the transmissivity of the liquid to be drawn up is lower than
in the liquid passage, judges that liquid exists in the liquid
passage.
[0052] According to the fourteenth aspect of the invention, the
judgement device, after detecting the liquid surface, can judge the
condition of the liquid during the operation of suction into or
discharge from the liquid passage, by analyzing the suction and
discharge operation by the pressure control device, as well as the
pattern composed of the light amount, the light intensity or the
image; temporal fluctuations of the light amount, the light
intensity or the image; or spatial distribution of the light
amount, the light intensity or the image, detected by the detecting
device.
[0053] A fifteenth aspect of the invention is that with any one of
the first aspect of the invention through the eleventh aspect of
the invention, the judgement device, in the condition where the
liquid is drawn up to lower than a predetermined height in the
liquid passage, by raising the liquid passage or lowering the
detecting device, judges the size of the volume drawn into the
liquid passage, based on the distance moved to where the liquid
surface in the liquid passage crosses the detecting location of the
detecting device, and information showing the relationship between
a predetermined optional distance from the suction aperture and the
capacity of the liquid passage.
[0054] According to the fifteenth aspect of the invention, the
judgement device, in the condition where the liquid is drawn up to
lower than the predetermined height in the liquid passage, by
raising the liquid passage, can judge the size of the volume drawn
into the liquid passage, based on the distance raised to when the
liquid surface in the liquid passage crosses the predetermined
height, and information showing the relationship between a
predetermined optional distance from the suction aperture and the
capacity of the liquid passage.
[0055] A sixteenth aspect of the invention is that with any one of
the first aspect of the invention through to the eleventh aspect of
the invention, the judgement device, in the condition where the
liquid is drawn into the liquid passage, by raising the liquid
passage or lowering the detecting device, detects the liquid
surface twice before it reaches the tip of the liquid passage, and
also in the condition where the liquid is drawn up to a higher
level than the predetermined height, by raising the liquid passage
or lowering the detecting device, judges a liquid shortage in the
case where a change is detected from the condition with liquid
present to the condition with liquid again absent.
[0056] According to the sixteenth aspect of the invention, the
judgement device, in the condition where the liquid is drawn into
the liquid passage, by raising the liquid passage, detects the
liquid surface twice before it reaches the tip of the liquid
passage, and also in the condition where the liquid is drawn up to
a higher level than the predetermined height, by raising the liquid
passage, can judge a liquid shortage in the case where a change is
detected from the condition with liquid present to the condition
with liquid again absent.
[0057] A seventeenth aspect of the invention is that with any one
of the first aspect of the invention through to the sixteenth
aspect of the invention, the dispenser also has a magnetic device
outside of the liquid passage capable of applying and removing a
magnetic field to and from each liquid passage, and the operation
instruction device also instructs the magnetic device to apply and
remove a magnetic field, and the judgement device also judges the
instruction result made by the magnetic field in relation to the
liquid passage.
[0058] According to the seventeenth or thirty-fifth aspect of the
invention, outside of the liquid passage, judgment can be made of
the operation of the magnetic device capable of applying and
removing a magnetic field to and from each liquid passage.
[0059] An eighteenth aspect of the invention is that with any one
of the first aspect of the invention through to the seventeenth
aspect of the invention, the liquid passage is a pipette tip
detachably mounted on a nozzle provided on the dispenser, and the
dispenser has a detaching device for the pipette tip, and the
operation instruction device also gives the transport device and
the detaching device an instruction to attach and detach the
pipette tip, and the judgement device judges the result of the
instruction of attaching and detaching the pipette tip.
[0060] According to the eighteenth aspect of the invention, the
liquid passage is a pipette tip detachably mounted on a nozzle
provided on the dispenser, and the detaching and attaching can also
be verified.
[0061] A nineteenth aspect of the invention is that a dispenser
operation verification apparatus according to any one of the first
aspect of the invention through the eighteenth aspect of the
invention, wherein a detection substance for aiding in or capable
of detection by the detecting means, is contained in the liquid
being sucked, discharged or stored in the liquid passages.
[0062] According to the nineteenth aspect of the invention, by
adding a detection substance to a liquid, detection can be surely
and accurately performed, and reliable verification of operations
is enabled.
[0063] A twentieth aspect of the invention is that a dispenser
comprising: one or a plurality of transparent or semi-transparent
liquid passages capable of liquid suction, discharge and storage; a
pressure control device for controlling the pressure in the liquid
passage; a transport device for effecting relative movement between
a container and the liquid passage; and an operation instruction
device for issuing operating instructions to the pressure control
device and the transport device, is used and verification of the
operation of the dispenser is effected by having; an operating step
for performing operations related to the liquid passage, a
detection step for detecting an optical condition of the liquid
passage, a movable region thereof or a part of that region, and a
judgement step for judging the result of the instruction related to
the liquid passage issued by the operation instruction device,
based on the optical conditions detected by the detection step.
[0064] In the twentieth aspect of the invention, an effect as
already explained for the first aspect of the invention is
demonstrated.
[0065] A twenty-first aspect of the invention is that with the
twentieth aspect of the invention, the judgement step judges the
result of the instruction, based on information besides the optical
condition, selected from amongst information containing; operation
information related to the operation instructions of the operation
instruction device, object information related to objects which the
dispenser draws in, discharges and stores, and device information
related to the dispenser including the liquid passage.
[0066] In the twenty-first aspect of the invention, an effect as
already explained for the second aspect of the invention is
demonstrated.
[0067] A twenty-second aspect of the invention is that with the
twenty-first aspect of the invention, the operation information
contains: suction amount or discharge amount; presence of suction
or discharge; speed of suction or discharge; suction and discharge
operation including time of suction or discharge; and/or
information on movement operation including movement path, movement
direction and/or movement distance, the object information contains
the kind or nature of liquid and/or the type and/or the presence of
suspensions such as magnetic particles and the like, and the device
information contains the nature and shape of the liquid passage
and/or information showing the relationship between the distance
from a suction aperture and the capacity of the liquid passage.
[0068] In the twenty-second aspect of the invention, an effect as
already explained for the third aspect of the invention is
demonstrated.
[0069] A twenty-third aspect of the invention is that with the
twentieth aspect of the invention, the detection step has a step
for receiving light at one or a plurality of locations, from the
liquid passage, the movable region or a part of the region.
[0070] In the twenty-third aspect of the invention, an effect as
already explained for the fourth aspect of the invention is
demonstrated.
[0071] A twenty-fourth aspect of the invention is that with the
twenty-third aspect of the invention, in the case where the liquid
passage is capable of upward and downward movement, and in the case
where the light receiving device is fixedly provided outside of the
upward and downward movement path of the liquid passage such that
an optical axis thereof is directed toward a predetermined height
location of the upward and downward movement path, the detecting
step detects the lower edge of the liquid passage and up to the
upper level to where the liquid can be stored while performing the
upward and downward movement by the transport device.
[0072] In the twenty-fourth aspect of the invention, an effect as
already explained for the fifth aspect of the invention is
demonstrated.
[0073] A twenty-fifth aspect of the invention is that in either one
of the twentieth aspect of the invention and the twenty-fourth
aspect of the invention, the detection step is performed by
receiving light emitted toward the liquid passage, the movable
region or a part of the regions
[0074] In the twenty-fifth aspect of the invention, an effect as
already explained for the sixth aspect of the invention is
demonstrated.
[0075] A twenty-sixth aspect of the invention is that with the
twentieth aspect of the invention, the detecting step is performed
by picking up an image of the liquid passage, a movable region
thereof or a part of the region.
[0076] In the twenty-sixth aspect of the invention, an effect as
already explained for the seventh aspect of the invention is
demonstrated.
[0077] A twenty-seventh aspect of the invention is that with the
twentieth aspect of the invention, the detecting step receives
light spanning the maximum width of the upward and downward
movement path so that the light from the maximum width of one or a
plurality of the upward and downward movement paths of the liquid
passage can be received or picked up.
[0078] In the twenty-seventh aspect of the invention, an effect as
already explained for the seventh aspect of the invention is
demonstrated.
[0079] A twenty-eighth aspect of the invention is that with the
twentieth aspect of the invention, the detecting step shines light
on the maximum width of one or a plurality of the upward and
downward movement paths of the liquid passage.
[0080] In the twenty-eighth aspect of the invention, an effect as
already explained for the seventh aspect of the invention is
demonstrated.
[0081] A twenty-ninth aspect of the invention is that with the
twentieth aspect of the invention, the judgement step judges
whether or not conditions related to the liquid passage corresponds
to the instruction result, by analyzing the optical pattern
composed of: the light amount, the light intensity or the image;
temporal fluctuations of the light amount, the light intensity or
the image; or the spatial distribution of the light amount, the
light intensity or the image, detected by the detecting step.
[0082] In the twenty-ninth aspect of the invention, an effect as
already explained for the tenth aspect of the invention is
demonstrated.
[0083] A thirtieth aspect of the invention is that with the
twenty-ninth aspect of the invention, conditions related to the
liquid passage in the judgment step include, the inaction or action
status of the liquid passage, and physical or chemical inaction or
fluctuation conditions of the contents of the liquid passage; the
condition of the liquid passage includes, the presence of a liquid
passage, the location of the liquid passage, the shape of the
liquid passage, and the nature such as transparency; the physical
condition of the contents of the liquid passage includes, the
presence of liquid in the liquid passage. the presence of the
surface or interface of the liquid in the liquid passage or the
location thereof, the amount of the liquid in the liquid passage;
the chemical condition in the liquid passage includes, the kind or
nature such as viscosity of the liquid in the liquid passage, air
bubbles in the liquid in the liquid passage or the presence of a
suspension such as magnetic particles or the concentration thereof,
the degree of suspension or mixing of the liquid in the liquid
passage, or a reaction condition such as light emission.
[0084] In the thirtieth aspect of the invention, an effect as
already explained for the eleventh aspect of the invention is
demonstrated.
[0085] A thirty-first aspect of the invention is that with the
twenty-fifth aspect of the invention, the judgment step judges, in
the case of a light emitting level where the amount or intensity of
the light received in the detecting step is almost the same as the
amount or intensity of the light from light emission, that there is
no liquid passage present, and in the case of a predetermined
shielding level where the amount or intensity of the light received
in the detecting step is smaller than the amount or intensity of
the light from the light emission, that a liquid passage is
present.
[0086] In the thirty-first aspect of the invention, an effect as
already explained for the twelfth aspect of the invention is
demonstrated.
[0087] A thirty-second aspect of the invention is that with the
twentieth aspect of the invention, the judgment step judges, based
on a time difference between a time that the pressure control
device is instructed to draw in a suction amount of liquid up to
the height of the liquid passage and a time that the amount or
intensity of the light detected in the detecting step actually
changes, a condition of liquid flow resistance or a condition of
blockage by foreign matter in the liquid passage.
[0088] In the thirty-second aspect of the invention, an effect as
already explained for the thirteenth aspect of the invention is
demonstrated.
[0089] A thirty-third aspect of the invention is that with the
twenty-ninth aspect of the invention, the judgement step, after
detecting the liquid surface by the detection step, judges the
condition of the liquid during the operation of suction into or
discharge from the liquid passage, by analyzing a suction and
discharge operation by a pressure control device, as well as an
optical pattern composed of: the light amount, the light intensity
or the image; temporal fluctuations of the light amount, the light
intensity or the image; or spatial distribution of the light
amount, the light intensity, or the image, detected in the
detecting step.
[0090] In the thirty-fourth aspect of the invention, an effect as
already explained for the fourteenth aspect of the invention is
demonstrated.
[0091] A thirty-fourth aspect of the invention is that with the
twentieth aspect of the invention, the judgement step, in the
condition where the liquid is drawn up to lower than a
predetermined height in the liquid passage, by raising the liquid
passage or lowering the detecting device, judges the size of the
volume drawn into the liquid passage, based on the distance moved
to where the liquid surface in the liquid passage crosses the
detecting location of the detecting device, and information showing
the relationship between a predetermined optional distance from the
suction aperture and the capacity of the liquid passage.
[0092] In the thirty-fourth aspect of the invention, an effect as
already explained for the fifteenth aspect of the invention is
demonstrated.
[0093] A thirty-fifth aspect of the invention is that with the
twentieth aspect of the invention, the judgement step, in the
condition where the liquid is drawn into the liquid passage, by
raising the liquid passage or lowering the detecting device,
detects the liquid surface twice before it reaches the tip of the
liquid passage, and also in the condition where the liquid is drawn
up to a higher level than the predetermined height, by raising the
liquid passage or lowering the detecting device, judges a liquid
shortage in the case where a change is detected from the condition
with liquid present to the condition with liquid again absent.
[0094] In the thirty-fifth aspect of the invention, an effect as
already explained for the sixteenth aspect of the invention is
demonstrated.
[0095] A thirty-sixth aspect of the invention is that with any one
of the twentieth aspect of the invention through to the
thirty-fifth aspect of the invention, the dispenser also has a
magnetic device outside of the liquid passage capable of applying
and removing a magnetic field to and from each liquid passage, and
the operation instruction device also instructs the magnetic device
to apply and remove a magnetic field, and the judgement step also
judges the instruction result made by the magnetic field in
relation to the liquid passage.
[0096] In the thirty-sixth aspect of the invention, an effect as
already explained for the seventeenth aspect of the invention is
demonstrated.
[0097] A thirty-seventh aspect of the invention is that with any
one of the twentieth aspect of the invention through to the
thirty-sixth aspect of the invention, the liquid passage is a
pipette tip detachably mounted on a nozzle provided on the
dispenser, and the dispenser has a detaching device for the pipette
tip, and the operation instruction device also gives the transport
device and the detaching device an instruction to attach and detach
the pipette tip, and the judgement step judges the result of the
instruction of attaching and detaching the pipette tip.
[0098] In the thirty-seventh aspect of the invention, an effect as
already explained for the eighteenth aspect of the invention is
demonstrated.
[0099] A thirty-eighth aspect of the invention is that with any one
of the twentieth aspect of the invention through the thirty-seventh
aspect of the invention, further comprises a step of adding a
detection substance for aiding in or capable of detection, to the
liquid being sucked, discharged or stored in the liquid passage
before the detection step.
[0100] In the thirty-eighth aspect of the invention, an effect as
already explained for the nineteenth aspect of the invention is
demonstrated.
BRIEF DESCRIPTION OF THE DRAWINGS
[0101] FIG. 1 is a block diagram showing the dispenser system
according to the embodiment of the present invention.
[0102] FIG. 2 is an overall structural diagram of the dispenser
according to the embodiment of the present invention.
[0103] FIG. 3 is a diagram showing a detecting device according to
the embodiment of the present invention.
[0104] FIG. 4 is a diagram showing the principal parts of the
dispenser according to the embodiment of the present invention.
[0105] FIG. 5 is diagram for explaining the detecting device
function according to the embodiment of the present invention.
[0106] FIG. 6 is diagram for explaining of a tip presence
verification operation by the detecting device according to the
embodiment of the present invention.
[0107] FIG. 7 is diagram for explaining of a liquid amount
verifying operation by the detecting device according to the
embodiment of the present invention.
[0108] FIG. 8 is diagram for explaining of a draw up verification
operation by the detecting device according to the embodiment of
the present invention.
[0109] FIG. 9 is diagram for explaining of a tip blockage
verification operation by the detecting device according to the
embodiment of the present invention.
[0110] FIG. 10 is diagram for explaining of a foam (or the like)
verification operation by the detecting device according to the
embodiment of the present invention.
[0111] FIG. 11 is diagram for explaining of a draw up verification
operation by the detecting device according to the embodiment of
the present invention.
[0112] FIG. 12 is diagram for explaining a liquid amount shortage
verification operation by the detecting device according to the
embodiment of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
[0113] Next is a description of embodiments of the present
invention based on the figures The present invention is not limited
to these embodiments unless specified.
[0114] FIG. 1 shows a dispenser system 1 according to the present
embodiments.
[0115] This dispenser system 1 comprises; a dispenser 10 which
dispenses liquid by drawing up and discharging liquid stored in a
container, an operation verification apparatus 11 for verifying the
operation of the dispenser 10, and an operation device 12 for
effecting input of various operation instructions and data with
respect to the dispenser 10 and the operation verification
apparatus 11, and also for displaying contents of operating
instructions, and the result of the operation verification and the
like for an operator.
[0116] Here, the operation device 12 comprises; a data input
section 13 including a keyboard, switches, a mouse, a touch panel,
a communication device, a CD drive, a floppy disk drive or the like
for entering the operation instructions and data, and a display
section 14 comprising a CRT, an LCD panel, a plasma display or the
like.
[0117] The dispenser 10 comprises: one or a plurality of
transparent or semi-transparent liquid passages 18 capable of
liquid suction, discharge and storage; a pressure control device 16
for controlling the pressure in the liquid passage 18; a transport
device 17 for performing upward and downward movement or horizontal
movement of the liquid passage 18 in relation to a container; a
magnetic device 23 provided outside of the liquid passage 18,
capable of applying and removing a magnetic field to and from the
liquid passage; a detaching device 24 for, in the case where the
liquid passage 18 is constituted by a pipette tip detachably
mounted on a nozzle in the dispenser 10, detaching the liquid
passage 18 from the nozzle; and an operation instruction device 15
comprising: a CPU for issuing operation instructions to the
pressure control device 16, the transport device 17, the magnetic
device 23 and the detaching device 24. The operation instruction to
be issued to the operation instruction device 15 is entered by the
operator using the operation device 12.
[0118] The operation verification apparatus 11 has: a detecting
device 20 for detecting the optical condition of the liquid passage
18, a movable region thereof or a part of the region; and a
judgement device 19, for judging, based on the optical condition
detected by the detecting device 20, the result of the instruction
related to the liquid passage 18 issued by the operation
instruction device 15, and outputting the result to the display
section 14 or other output device which is included in the
operation device 12, for example, a printing device, a
communication device, a floppy disc or the like, and optionally
executing instructions for feedback to the operation instruction
device 15 based on the result.
[0119] The judgement device 19 has a data storage section 21
comprising a memory device, a hard disc, an external memory device
or the like, and a computing section 22 comprising a CPU, a
sequencer or the like. The data storage section 21 stores, in
advance or by entry from the operation device 12, information
selected from amongst operation information related to the
operation instruction from the operation instruction device 15,
object information related to; the object that the dispenser draws
in, discharges or stores, and device information related to the
dispenser including the liquid passage. The computing section 22,
based on the optical condition detected by the detecting device 20,
the information selected from amongst the information stored in the
data storage section 21, the operation information directly
obtained from the operation instruction device 15, or the
information input from the data input section 13, by computing,
judges the condition related to the liquid passage. The computing
section 22, for example, when making judgements, judges based on
the object information or the device information stored in the data
storage section 21 and input from the data input section 13, by
comparing a standard optical condition obtained previously or by
computing with the optical condition detected by the detecting
device 20.
[0120] As follows is a more detailed description of each
constituent.
[0121] FIG. 2 is a front view showing a dispenser 10 according to
the present embodiment.
[0122] The dispenser 10 has a plurality of sets (in this example,
8) of nozzles 30.sub.1-30.sub.8, and a plurality of pipette tips
18.sub.1 (although there are 8 sets, sets 18.sub.2-18.sub.8 are
omitted from the figure for simplification) serving as transparent
or semi-transparent liquid passages 18 attached to the lower ends
of the nozzles 30.sub.1-30.sub.8.
[0123] In the figure, there is provided beneath the pipette tips
18.sub.1, a magnetic device 23 capable of applying and removing a
magnetic field to and from each of the pipette tips
18.sub.1-18.sub.8 when the pipette tips 18.sub.1 are lowered. The
magnetic device 23 has a permanent magnet 63 for applying a
magnetic field to the interior of each of the pipette tips
18.sub.1-18.sub.8 from the outside, and a slide plate 62 capable of
sliding the permanent magnet 63 backward and forward (in the
figure) to approach or recede from the pipette tips
18.sub.1-18.sub.8. Furthermore, as shown by the hatching in the
figure, a detecting device 20 of the operation verification device
11 for verify the operation of the dispenser 10, is located just
above the magnetic device 23 The pipette tips 18.sub.1-18.sub.8
comprise: a small diameter part and a large diameter part; or a
small diameter part, an intermediate diameter part and a large
diameter part, and the magnetic device 21 is for applying a
magnetic field to the small diameter part or the intermediate
diameter part.
[0124] The nozzles 30.sub.1-30.sub.8 are installed in an 8-set
nozzle unit 32 with an 8-set nozzle block base 31 supporting them.
Each of the pipette tips 18.sub.1-18.sub.8, attached to the lower
end of the nozzles 30.sub.1-30.sub.8 installed in the 8-row nozzle
unit 32, is moved up and down by the transport device 17, relative
to a base member 33 (column in the figure) of the dispenser 10,
which supports the container, the detecting device 20 and the
magnetic device 23 The transport device 17 comprises a pulley 34
driven by a stepper motor serving as a driving source (not shown in
the figure), a ball screw 35 driven by a rotation force from the
pulley 34, and a slide pipe 36 for guiding the upward and downward
movement in the vertical direction. The 8-set nozzle unit 32 in
which the nozzles 30.sub.1-30.sub.8 and the like are installed, is
moved up and down by the rotational drive of the ball screw 35.
[0125] Furthermore, a plunger (not shown in the figure), is
installed in the nozzles 30.sub.1-30.sub.8, so as to be slidable up
and down, for the suction and discharge operations by controlling
the pressure inside of the pipette tips 18.sub.1-18.sub.8. A
stepper motor 37, serving as a drive source for driving the plunger
is fixedly provided on the 8-set nozzle block base 31 by means of a
supporting member 38 provided upright from the 8-set nozzle block
base 31 of the 8-set nozzle unit 32. The rotating spindle of the
stepper motor 37 is connected to a ball screw 40 via a coupling 39.
A nut 41 is threaded onto the ball screw 40 so that the 8 set
plungers is supported on a nut 41. Moreover, with the nut 41 there
is provided a sliding bush 43, and the sliding bush 43, which
slidingly mates with a slide pipe 42, guides the movement of the
plunger up and down.
[0126] In the figure, numeral 44 denotes an origin sensor for
detecting the origin of the upward and downward movement of the
plunger, and numeral 45, denotes a limit sensor for the plunger
operation. Both are installed on the column 33. Here, the stepper
motor 37, the ball screw 40 and the like correspond to the pressure
control device 16.
[0127] In the figure, numeral 46 denotes a tip off plate for
detaching the pipette tips 18.sub.1-18.sub.8 from the nozzles
30.sub.1-30.sub.8, and numeral 47 denotes a tip off verification
sensor for verifying the detachment of the pipette tips
18.sub.1-18.sub.8. These constitute the detaching device 24. Here,
the whole of the dispenser 10 is stored inside of a casing provided
with an opening in a lower part of a front face so that the pipette
tips 18.sub.1-18.sub.8 can be observed from outside.
[0128] FIG. 3 shows the details of an optical sensor unit serving
as the detecting device 20 according to the present embodiment. As
shown in FIG. 3, the detecting device 20, which is an optical
sensor, comprises light emitting elements 50.sub.1-50.sub.8 using
LEDs, and light receiving elements 51.sub.1-51.sub.8 using photo
diodes. These light emitting elements 50.sub.1-50.sub.8 and light
receiving elements 51.sub.1-51.sub.8 are provided at a
predetermined height corresponding to outside of an upward and
downward movement path corresponding to a movable region of each of
the pipette tips 18.sub.1-18.sub.8, so as to form respective pairs
on either side of the path for each of the pipette tips
18.sub.1-18.sub.8. Here, "predetermined height" is a location
through which the lower end of the pipette tips 18.sub.1-18.sub.88
and up to an upper level to where the liquid can be stored, can be
passed through by the transport device 17.
[0129] The light emitting elements 50.sub.1-50.sub.8 and the light
receiving elements 51.sub.1-51.sub.8 are fixed to a supporting
member 52. Sufficient space is provided between opposite sides 52a
and 52b of the supporting member 52 for the pipette tips
18.sub.1-18.sub.8 to pass through. Pairs of holes 54 and 53 are
made, one in each side 52a and 52b along the optical axis for each
transport path of the pipette tips 18.sub.1-18.sub.8.
[0130] Furthermore on a base 60 of the detecting device 20, as
shown in FIG. 3, an amplifier 58 for amplifying the light detected
by the detecting elements 51.sub.1-51.sub.8, a control connector
55, a power connector 56, a gain adjustment trimmer 57 and an A/ID
converter 59 are respectively provided.
[0131] FIG. 4(a) is an external plan view of the detecting device
20, and FIG. 4(b) is a side view of the lower part of the dispenser
10.
[0132] The slide plate 62 of the magnetic device 23 is supported
and slides in a channel 64 provided on a side plate 61 made of
aluminum or the like. Near a front edge of the slide plate 62, a
drip receiver 65 is fitted, which is a shaped hollow or tray for
receiving drips from the ends of the pipette tips
18.sub.1-18.sub.8. A rack 66 is provided to the rear of the slide
plate 62 and meshed with a pinion 67. The pinion 67 is fixed to the
same spindle as that of a belt pulley which is connected to a
rotating spindle of a motor 69 via a belt 68, and thus rotated by
the motor 69. Here, in the figure, numeral 70 denotes a sensor
cover. In FIG. 4(a), parts covered by the sensor cover 70 are shown
by perspective. Besides, numeral 71 denotes a position sensor for
the slide plate 62. Numeral 72 denotes a member for supporting the
side plate 61 and so on.
[0133] With the above construction, the results of the various
operation instructions issued to the pressure control device 16,
the transport device 17, the magnetic device 23, and the detaching
device 24 are judged based on the optical condition detected by the
detecting device 20. The obtained result of the judgement is, for
example, displayed on the screen of the display section 14 to
inform the user.
[0134] FIG. 5(a) is a plan view showing the principle outline of
the detecting device 20 according to this embodiment, and FIG. 5(b)
is a side view. The detecting device 20 comprises light emitting
elements 50.sub.1-50.sub.8 and light receiving elements
51.sub.1-51.sub.8. The light emitting elements 50.sub.1-50.sub.8
and the light receiving elements 51.sub.1-51.sub.8 are set in
opposing locations to each other along the optical axes shown by
dotted lines in the figure for each of the pipette tips
18.sub.1-18.sub.8, outside of the upward and downward transport
path of the pipette tips 18.sub.1-18.sub.8, with the path of the
pipette tips 18.sub.1-18.sub.8 therebetween.
[0135] The pipette tips 18.sub.1-18.sub.8 (hereafter with
subscripts omitted), as shown in FIG. 5(a), move upward and
downward, and the light emitting elements 50.sub.1-50.sub.8
(hereafter with subscripts omitted) and the light receiving
elements 51.sub.1-51.sub.8 (hereafter with subscripts omitted) are
fixedly provided at a predetermined height location of the upward
and downward transport path.
[0136] FIG. 6 shows the case where the detecting device 20 judges
the presence of the pipette tip 18 to verify the operation.
[0137] FIG. 6(a) shows the case where the tip 18 is not attached.
In this case the light from the light emitting element 50 is
observed without change as light amount I.sub.0 by the light
receiving element 51 as shown in the optical pattern in FIG. 6(c).
In the case where the tip 18 is attached as in FIG. 6(b), the
result is that the light from the light emitting element 50 is
absorbed and scattered, and light amount I.sub.1 is observed by the
light receiving element 50 as shown in the optical pattern in FIG.
6(c). The judgement device 19, by comparing the operation
instruction and the detected optical pattern, instructs the display
section 14 to display affirmative or negative.
[0138] FIG. 7 shows the case where the presence of liquid in the
pipette tip 18 is judged to verify the operation.
[0139] FIG. 7(a) shows the condition when liquid is not drawn into
the pipette tip 18. In this case, because the air in the tip 18 has
a low refractive index, all of the light from the light emitting
element 50, passing through the tip cannot be collected since the
lens effect is not large, and as shown in the optical pattern in
FIG. 7(c), the light amount 11 is received.
[0140] Conversely, as shown in FIG. 7(b), in the condition when
liquid is drawn into the pipette tip 18, the light of the light
emitting element 50 converges according to the same principle as
for a cylindrical lens since there is liquid with a high refractive
index in the tip 18 As a result, as shown in the optical pattern in
FIG. 7(c), a far higher light amount 12 is received compared to the
light amount I.sub.1 for the case with no liquid inside. Here the
above description has been for the case of liquid with high light
transmissivity.
[0141] On the other hand, in the case of liquid with low light
transmissivity, in other words a liquid with high light absorption,
most of the light passing through the tip 18 is absorbed.
Therefore, as shown in the optical pattern in FIG. 7(d), for the
light intensity or light amount observed, a light amount 12, which
is lower than the light intensity or light amount II for the case
where there is no liquid is observed. Accordingly, in the case
where the liquid is known in advance to have low light
transmissivity, the presence of the liquid can be judged by
observing the low light amount.
[0142] Furthermore, liquid such as a suspension of small beads or
blood serum can be reliably detected using the lens effect, by
selecting visible light where the wavelength of the light of the
light emitting element is 600 nm or more to prevent absorption by
the liquid.
[0143] Moreover, in the case where whole blood or a suspension with
an extremely high concentration of beads is used, the lens effect
and light extinction by absorption counteract, which sometimes
makes it difficult to detect. In this case, by dissolving a
coloring matter in the solution that absorbs the wavelength of the
light source being used, the light amount is decreased to less than
I.sub.O, enabling accurate detection. In this way, in the case
where the nature of the liquid being drawn up is known in advance,
it is possible to detect accurately by the change in the observed
value, that the liquid is drawn up.
[0144] FIG. 8 shows the case where the detecting device 20 judges
the passing of the liquid surface in the pipette tip 18, to verify
the operation.
[0145] In the case where, in the condition where the height of the
tip is fixed and a high light transmissivity liquid such as a
reagent or the like is drawn up, then as shown in FIG. 8(a), in the
condition where the liquid surface does not go past the sensor
axis, the light intensity is low, as shown in FIG. 8(c).
Immediately after the liquid surface passes through, as shown in
FIG. 8(b), the light intensity or the light amount increases as
shown in the optical pattern in FIG. 8(c). Accordingly, if a change
in the light amount is observed during the drawing up operation, it
can be judged that the time of the change is the time when the
liquid surface passes. On the other hand, in the case where a low
light transmissivity liquid is drawn up, immediately after the
liquid surface passes, the light intensity or the light amount
decreases.
[0146] FIG. 9 shows the case where the liquid flow resistance or
viscosity is judged, to verify the operation.
[0147] In this case, if the drawn up amount when the liquid surface
in the tip 18 is on the optical axis is measured in advance, the
flow resistance of the configuration can be known from a
correlation of the passing through of the liquid surface and the
operation position of the plunger.
[0148] In the case where the liquid is drawn up using the pressure
control device 16, the timing of the passing through of the liquid
surface is delayed more when drawing up a high viscosity liquid
than a low viscosity liquid like water, as shown in the optical
pattern in FIG. 9 (c). Also in the case of drawing up water, when
the end of the tip is pressed to the bottom of the liquid container
or the end of the tip is blocked with foreign matter, the timing is
delayed. In the case where the tip is completely blocked, the
liquid surface cannot be detected however strongly the pressure
control device 16 is operated.
[0149] FIG. 10 shows the case where the detecting device 20 detects
the presence of foam or flocculent or suspension in the liquid
drawn into the pipette tip 18.
[0150] As shown in FIG. 10(a), in the case where a flocculent such
as foam, protein or the like is mixed in a liquid such as a reagent
or the like, then since as shown in the optical pattern in FIG.
10(b), the suction and discharge operation by the pressure control
device 16 as well as the measurement data fluctuate greatly, the
intermixing can be detected by the fluctuation value after
detecting the liquid surface. Moreover, after the liquid is drawn
up, by repeating the suction and discharge operation by the
pressure control device 16, the fluctuation amount of the measured
value can be obtained.
[0151] FIG. 11 shows the case where the detecting device 20
verifies the liquid amount drawn into the pipette tip 18.
[0152] In the condition with the liquid drawn up to below the
sensor optical axis as shown in FIG. 11(a), when the pipette tip 18
is moved upward, then as shown in FIG. 11(b), at a certain time the
liquid surface inside the tip 8 crosses the optical axis. As shown
in the optical pattern in FIG. 11(c), by comparing the Z-axis
coordinate when the sensor detects the liquid level, with
translation data for the Z-axis coordinate and the liquid amount
obtained in advance and stored in the data storage section 21, the
liquid amount in the tip 18 can be determined.
[0153] FIG. 12 shows the case where the detecting device 20 can
verify a shortage in the liquid amount of the liquid drawn into the
pipette tip 18.
[0154] As shown in FIG. 12(a), in the case where the liquid drawn
up is insufficient, air enters the end of the tip 18. Accordingly,
in the condition where a reagent is drawn up, then as shown in FIG.
12(b), if the pipette tip 18 is moved upward along the Z axis, the
two liquid surfaces are detected before reaching the end of the tip
18. That is to say, in the condition where the liquid is drawn up
to the sensor optical axis or higher, if the Z axis is moved
upward, then as shown in the optical pattern in FIG. 12(c), the
condition changes from the condition for the presence of a reagent
back to the condition for the absence of a reagent.
[0155] In the case where the liquid which the pipette tip 18 draws
up according to the embodiment is semi-transparent with respect to
the observing light source, this is also applicable. In the case of
a semi-transparent liquid, depending on the light transmissivity,
light convergence by the lens effect and light extinction by
absorption and scattering counteract so that there is a possibility
of difficulty in clearly distinguishing the light amount of the tip
18 itself. In this case, by mixing in advance in the liquid to be
drawn up, coloring matter that has sufficient absorption for the
wavelength to be observed, enables an accurate distinction
[0156] Each of the above-described embodiments is described
specifically for the purpose of better understanding the present
invention, and does not exclude other embodiments. Accordingly,
modification is possible within the scope in which the gist of the
invention is not changed. For example, in the above explanation,
the nozzle and pipette tip are movable up and down by the transport
device, and the detecting device is described for the case where
the light emitting element and light receiving element are fixed.
However, the nozzle and the pipette tip may be movable horizontally
as well, and it is also possible for the nozzle and the pipette tip
to be fixed and for only the container to move. In that case, the
light emitting element and the light receiving element of the
detecting device would be movable. Furthermore, the light that the
light emitting element emits is described for the case of visible
light, however, it is not restricted to the case of visible light,
and infrared light, ultraviolet light or the like can be used.
Moreover, by fitting a filter in front of the light emitting
device, it is possible to emit various wavelengths of light.
[0157] Furthermore, according to the above explanation, the light
emitting device and the light receiving device are used as the
detecting device, however, it is possible to use an image pick-up
device. Moreover, in the above explanation, the verification of the
operation by the magnetic device is not explained, however, it is
possible to verify the result of applying and removing a magnetic
field by the magnetic device. The above example is described for
the case where a pipette tip is detachably mounted on a nozzle,
however, it is possible that the nozzle itself is a transparent or
semi-transparent liquid passage without a pipette tip.
[0158] According to the above explanation, the judgement result is
described only in the case of displaying this on the display
section to inform the operator, however, it is possible to inform
by other means such as an alarm sound, voice or the like.
Furthermore, it is possible, based on the judgement result
obtained, to use feedback to control the operation, by sending a
signal to the operation instruction device 15.
[0159] Moreover, in the above explanation, the light emitting
device of the detecting device is limited to one kind, however, it
is possible to emit light by selecting from a plurality of light
emitting device depending on the object of the verification such as
the liquid type or the like, by instructions from the operation
section, or to insert and remove a plurality of filters between the
light emitting device and the liquid passage. Furthermore, in the
above explanation, as the magnetic device, a magnet provided so as
to be able to approach and recede from the pipette tip is used,
however, it is possible to use a means whereby turning an
electromagnet on or off applies and removes a magnetic field to and
from inside the liquid passage. Moreover, the invention is not
limited to the 8-set nozzles, and by providing two or more of the
light receiving device or image pick-up device, it is also
applicable to a dispenser in which the nozzles are arrayed in
matrix form.
* * * * *