U.S. patent number 3,645,142 [Application Number 05/085,056] was granted by the patent office on 1972-02-29 for pipette system.
This patent grant is currently assigned to Hoffmann-La Roche, Inc.. Invention is credited to Pierre Turpin.
United States Patent |
3,645,142 |
Turpin |
February 29, 1972 |
PIPETTE SYSTEM
Abstract
An apparatus for transferring a specific quantity of a liquid
medium from one receptacle to another with precision. The apparatus
comprises a series of movable canals operatively disposed between
the same container and the receptacle to which the same is to be
transferred. In a preferred aspect, the device is designed to
transfer samples taken from human subjects, which samples are to be
tested for diagnostically significant features.
Inventors: |
Turpin; Pierre (Burs S/Yvette,
FR) |
Assignee: |
Hoffmann-La Roche, Inc.
(Nutley, NJ)
|
Family
ID: |
9042507 |
Appl.
No.: |
05/085,056 |
Filed: |
October 29, 1970 |
Foreign Application Priority Data
Current U.S.
Class: |
73/864.12;
422/561 |
Current CPC
Class: |
G01N
1/38 (20130101) |
Current International
Class: |
G01N
1/38 (20060101); G01n 001/14 () |
Field of
Search: |
;73/425,4P,426
;23/259,292 ;141/18,25,26,27,28 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Swisher; S. Clement
Claims
I claim:
1. A pipette system for transferring a desired volume of a liquid
sample from a sample container in which it is stored into a
receiving receptacle which comprises a distribution means including
a first member having formed therein at least two independent,
noncommunicating canals, the ends of which open at the periphery of
the first member and a second member movable with respect to the
first member, said second member being traversed by at least four
noncommunicating openings, each canal when in operative condition
being in communication with two of said openings, a sampling means
adapted to be immersed into the container and joined to said
distribution means, said sampling means having an opening therein
in communication with a first of said openings, a depressurized
evacuating container connected to a second of said openings, a
reservoir connected to a third of said openings, a source of
compressed gaseous material connected to a fourth of said openings,
one of the canals in the first member in a first operative position
being in communication with a first and a second of said openings
thereby forming a passageway leading to the evacuating container,
into which passageway the sample is withdrawn from the sample
container, another of said canals being in communication with a
third and fourth of said openings, thereby forming a passageway
therewith, means for moving said first member relative to said
second member from said first operative position to another
operative position, said one of said canals in said another
operative position being in communication with said first and third
openings thereby forming a passageway therewith whereby gaseous
material contained in the reservoir causes sample liquid contained
in the sampling means to be decanted into the receiving
receptacle.
2. A pipette system in accordance with claim 1 characterized by the
fact that the said means for moving the first member of the
distribution system relative to the second member includes a motor
means of the step-by-step type thereby permitting incremental
movements, said motor means being energized in response to commands
given by a liquid detector, said liquid detector being positioned
in the system between the depressurized container and the said
second of the openings and being responsive to passage of the
liquid sample through the said passageway into which it is
withdrawn.
3. A pipette system in accordance with claim 2, characterized by
the fact that it includes a valve placed between the depressurized
container and the liquid detector, the opening and the closing of
said valve being controlled by the detector.
4. A pipette system in accordance with claim 1 characterized by the
fact that the two members of the distribution means are movable
rotatively relative to each other, and the said at least four
openings are spaced equidistant one from another.
5. A pipette system in accordance with claim 1 characterized by the
fact that it comprises a cleaning liquid conduit for entry of a
cleaning liquid operatively connected to the said fourth of said
openings between the latter and said source of gaseous material,
said cleaning liquid conduit having a valve disposed in the path of
the passageway provided by the interior of the cleaning liquid
conduit, and an inlet conduit and outlet conduit operatively
connected to the said second of said openings between the said
second opening and the depressurized evacuating container, a source
of drying gas connected to the inlet conduit, said outlet conduit
being adapted to permit the escape of the drying gas and first and
second valve means on said inlet and outlet conduits and disposed
in the entering and escape path, respectively, of the drying gas
and adapted to control the entry and escape of the drying gas.
6. A pipette system in accordance with claim 1, characterized by
the fact that the reservoir comprises at least two reservoir
chambers connected in series via a valve means adapted to control
delivery to the reservoir chambers.
7. A pipette system in accordance with claim 1 in which the first
member is a rotor and the second member is a stator which rotatably
receives the rotor.
8. A pipette system in accordance with claim 1 characterized by the
fact that the second member of the distribution means includes a
fifth and sixth opening, said fifth and sixth openings adapted to
communicate with a third canal in the first member in the said
first operative positions, one of said last-mentioned fifth and
sixth openings being connected to a source of cleaning liquid and
the other being connected to an evacuating depressurized
vessel.
9. A pipette system as in claim 8 wherein the distribution means
additionally includes an additional pair of openings in the second
member, which pair of openings communicate with a fourth canal in
said first member in the first operative position, one of said
last-mentioned pair of openings being connected to a source of
drying air and the other being connected to an exhaust.
10. A pipette in accordance with claim 1 wherein the sampling means
includes a hollow needle coated all along its internal surface and
at least partially along its external surface with a
water-repellent coating.
11. A pipette system as in claim 1 wherein the water-repellent
coating is silicon based.
12. A pipette system in accordance with claim 1 wherein the said
openings and said canals can be moved to a position between the
first operative position and the second operative position wherein
the open ends of the canals do not communicate with the said
openings in the second member.
13. A pipette system for the sampling of a calibrated volume of a
liquid substance contained in a first container and for the
transfer of this volume and an additional calibrated volume of a
dilution liquid into a receiving receptacle, characterized by the
fact that it comprises a first and a second distribution means,
each including a first member and a second member, each of said
first members having formed therein at least two independent
noncommunicating channels, the ends of which open at the periphery
of the first member, said second members being movable with respect
to the first members, each of said second members being provided
with at least four transverse openings extending through the second
member, each channel being adapted to be placed in communication
with two of said openings, a sampling means integral with the first
distribution means and connected to a first of said openings in the
second member of the first distribution means, a first
depressurized container connected to a second opening in the second
member of the first distribution means adjacent to the said first
opening, a second depressurized container connected to a third
opening in the second member of the first distribution means
adjacent to the last-mentioned second opening, a fourth opening in
the second member of the first distribution means, and being
connected via a conduit having a calibrated internal volume to a
first opening in the second member of the second distribution
means, a second opening in the said second member of the said
second distribution means adjacent to the first opening, said
last-mentioned second opening being connected to a reservoir, a
third opening in the second member of the said second distribution
means adjacent to the last-mentioned second opening and being
connected to a source of compressed gas and a fourth opening in the
second member of the second distribution means connected to a
source of a dilution liquid.
Description
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an apparatus for transferring a
predetermined amount of a liquid sample from a sample container
into a receiving receptacle. The liquid transferred to the
last-mentioned receptacle is destined to be fed into a machine
which analyses such liquids for significant features.
Most preferably, the sample fluids which are to be analyzed are of
human origin such as blood, urine and the like. Thus, such samples
are to be analyzed for diagnostically significant features.
Since the advent of automated analysis techniques and the
widespread practice of screening in order to determine at an early
stage, the presence of physiological abnormalities, the need to
provide an apparatus which can rapidly and efficiently feed
predetermined amounts of a sample into a machine adapted to
automatically analyze the sample for a desired characteristic,
should be readily apparent. It is the object of this invention to
provide a means whereby this end can be effected.
More precisely, the present invention concerns an automated
precision pipette system so constructed and arranged as to effect
the transfer of a calibrated volume of a liquid from a first
receptacle to a second.
Particularly in the field of chemical analysis, industrial chemical
analysis, biochemical analysis and the like, the need often exists
for transferring a carefully measured volume of a liquid from a
first receptacle in which it is stored into a second receptacle
containing, for example, a reagent. The present invention has for
its object the provision of a pipette system, which permits the
transfer of predetermined small quantities of liquids, for example,
a few microliters, from one receptacle or container to another.
Another object of the present invention is the provision of an
automatic pipette system, which permits a rapid sequence of
functions whereby the pipette system performs at a high rate of
speed in a precise consistent manner, e.g., withdraws rapidly from
a multitude of samples, a constant measured volume thereof at the
rate of one withdrawal per second.
Another aim of the invention is the provision of a pipette which
permits the transfer of a sample from one container to another
without being contaminated by residue from previously transferred
liquids. Particularly, with human samples destined for human
analysis, the necessity of avoiding cross contamination between
samples should be evident.
In order to achieve these objectives, the present invention
includes a pipette system adapted to transfer a calibrated or
measured volume of a liquid substance from a first container in
which it is stored into a second receptacle. The liquid contained
in the second receptacle is to be fed into an automatic analyzing
machine. The pipette system is characterized by the fact that it
comprises an internal distribution means comprising a first member
transversed by two separated noncommunication canals and a second
member movable with respect to the said first member, said second
member being provided with four openings traversing the second
member. Each of the two canals in the first member in operative
position is in communication with corresponding pairs of the
openings in the second member. The internal distribution means,
preferably comprises an outer hollow cylindrical stator member (the
second member) and an inner rotatable rotor core (the first
member). The outer hollow cylindrical member is provided with four
transfer openings or passages extending from its inner surface to
its outer surface. The inner rotor core is provided as is noted
above with two independent noncommunicating canals which traverse
the inner core member. The two ends of each canal are opened at the
exterior of the rotor core. The open ends of the two canals, when
in operative condition, are adapted to communicate with adjacent
openings in the outer cylindrical member, thereby permitting a flow
of liquid through the passageway, so obtained.
The invention will be better understood by the description of the
various modes of carrying out the invention set forth hereinafter.
These and other objects, features and advantages will be apparent
upon consideration of the following disclosure taken in conjunction
with the accompanying drawings in which:
FIGS. 1a and 1b represent schematically a first embodiment of the
pipette system respectively showing the positioning of the various
members of the pipette system at the start and about the finish of
the transfer operation.
FIG. 2 represents schematically a pipette system in accordance with
that in FIG. 1 and provided with a cleaning and drying means.
FIG. 3 is a schematic view illustrating another embodiment of the
present invention.
FIGS. 4a, 4b and 5 represent schematically still other embodiments
of the pipette system in accordance with the present invention.
FIGS. 1a and 1b represent schematically one preferred embodiment of
the invention. FIG. 1a illustrates the said embodiment during the
starting phase of the transfer operation. FIG. 1b shows the device
at about the completion of the transfer operation.
The pipette system is designed to extract a measured quantity of a
liquid 10 contained in a container 11 and to inject the measured
amount into a receptacle 12.
The pipette system of the present invention includes in combination
a hollow needle 1, for example, of the hypodermic type. The hollow
needle 1 is fixedly joined to a distribution means 7 (rotary valve
or sluice 7). A reservoir 3 is fixedly secured to the valve 7.
Valve 7 is also connected to an evacuating container 4; the
interior of which is under reduced pressure. That is to say, the
container is maintained below atmospheric pressure. A stop valve 5
and a liquid detector 8 are disposed between the depressurized
container 4 and valve 7. The container 4 may be replaced by any
suitable pumping mechanism.
The internal volume of the hollow needle is equal in volume to the
volume of that portion of the sample required for precision
analysis. The needle 1 is advantageously coated all along its
internal surface and at least partially along a portion of its
external surface extending from the free end thereof, with a layer
of a water-repellent material such as a silicon. By the utilization
of a hydrophobic material, it is assured that no substantial
portion of the sample liquid will adhere to the needle after the
transferring operation is completed. Valve 7 is presented in the
Figures as having a rotatable inner core. It should be evident,
however, that without departing from the scope of the invention,
there could be utilized any equivalent distribution valve of a
different type provided that it functions in the same manner as the
rotary form of valve 7 described herein.
The needle 1 is fixedly secured at its upper end to valve 7 by any
appropriate means, i.e., a force-fit or the like. The valve 7, as
is indicated above, in the preferred aspect comprises a rotatable
inner member, namely, rotor 70. Rotor 70 has formed therein two
internal noncommunication independent canals 71 and 72. Canals 71
and 72 extend through the rotor 70 to the periphery thereof. In the
embodiment illustrated in FIGS. 1a and 1b, the entrances to the
canals are spaced 90.degree., one from the other. The outer member
73 contains four openings 711, 712, 721 and 722. The four openings
are disposed about the stator 73 at an angle of 90.degree., one
from the other.
Thus, as seen in FIG. 1a, the needle 1 is disposed below the
opening 721, while the opening 722 is connected to the evacuating
means 4 by a conduit 40. Disposed in the path of the internal
passage in conduit 40 is a valve 5. Adjacent valve 5 and
operatively connected thereto is a liquid passage detector 8.
Detector 8 is positioned in the pipette system between stop valve 5
and opening 722 as shown in FIG. 1a. Detector 8 controls the
opening and closing of valve 5. The opening 711 in the outer member
73 is connected to a source of compressed gas 2 (for example,
atmospheric air under pressure or a bottle of nitrogen) by a
flexible conduit 20. Finally, the opening 712 as seen in FIG. 1 is
connected to a small expansion reservoir or tank 3 via conduit
30.
The apparatus performs its designated function in the following
manner.
At the beginning of the operation, the valve 7 occupies the
position indicated in FIG. 1a and the valve 5 is opened. The needle
1 is immersed into the liquid 10 to a predetermined, calibrated
depth. The valve 7 is in a position whereat the opening in conduit
40 communicates with canal 72 which in turn is in communication
with the opening in hollow needle 1. A passageway extending from
vessel 4 to container 11 is therefore provided. The liquid 10
passes through needle 1 under the influence of the vessel 4, and
then through canal 72 into conduit 40. When the liquid reaches the
detector 8, detector 8 gives a command directing that valve 5 be
closed. Upon closing of valve 5, the liquid 10 rests in suspension
in the needle 1, the canal 72 and the portion of the conduit 40
extending from valve 7 to stop valve 5. It should be noted that the
detector 8 need not necessarily be precisely positioned in the
system since it is only the liquid contained in the needle which is
to be transferred. Also, the valve 5 need not be of a precision
type for the same reason. The detector also commands the mechanism
which effects movement of the rotor 70 and the pipette system per
se.
When the liquid is entering the needle 1, the reservoir 3 which is
in communication with the gaseous source 2 adjusts to the pressure
of this source via the canal 71 and conduits 20 and 30.
For the needle 1 to be transferred from the position thereof shown
in FIG. 1a to the position thereof shown in FIG. 1b, the pipette
system is transported as a whole to a position whereat needle 1 is
above the receptacle 12 by any suitable means. If the receptacle 12
is closed, (e.g., if a closed pouch is used) the needle can be
conveniently adapted either by designing it to be able to partake
of a supplementary translational movement in order to pierce the
receptacle wall. The rotor 70 is then turned a quarter of a turn
clockwise, i.e., through an angle of 90.degree.. The movements of
the rotor 70 can be effected by a motor of the step-by-step type.
Alternatively, rotor 70 can move through a smaller angle, namely
one-eighth one-sixteenth or smaller increments of a complete
360.degree. turn. By having the rotor 70 move through such smaller
increments under the influence of the step-by-step type motor, the
motor 70 can have an intermediate position between that shown in
FIGS. 1a and 1b at which the canals or channels 71 and 72 are not
in communication with the openings 711, 712, 721 and 722. In this
case, the passage from the first position (FIG. 1a) into the second
position (FIG. 1b) will be accomplished by several successive
movements of the step-by-step motor.
In the position shown in FIG. 1b, the volume of the liquid
contained in the needle which is forced by the compressed air of
the reservoir 3 which expands in accordance with adiabatic law.
Simultaneously, the liquid contained in canal 72 and communicating
conduit 40 is drawn into the evacuating vessel 4 from which it is
discarded. Thus, vessel 4 serves as a draining receptacle for the
sample liquid which is not utilized in the subsequent analysis
procedure.
The volume of the liquid transferred from the container 11 into the
receptacle 12 is precisely determined by the volume of the needle
(including, of course, the amount contained in the opening 721 in
the outer cylindrical member 73). In any event, the volume
transferred from opening 721 and the needle 1 is easily calculated
and can be kept constant and ascertainable with accuracy. Taking
into account the slight volume found in opening 721, the precise
amount of liquid is obtained by the fact that canal 72 is cut off
from communication with opening 721 as the device moves from the
position shown in FIG. 1a to that shown in FIG. 1b.
The pressure in the reservoir 3 decreases exponentially. Thus, the
force exerted on the liquid is maximal at the beginning of the
decantation and weak at the end of the operation. As a consequence
of this, the needle is quickly emptied of liquid and excessive
bubble formation is avoided. The draining off and cleansing of the
canal 72 and conduit 40 are assured by the jet of air derived from
the compressed gas 2 being forced into the passageway provided when
canal 72 and conduits 20 and 40 are in communication.
Valve 5 can be regulated whereby it will close when specified
volumes of gas enter the evacuating container 4. The force which is
exerted on the liquid and the needle can be adjusted by regulating
the amount of compressed air 2 entering the system with the volume
of container 3 in view. In certain cases, it will be desirable to
utilize a pressure reducer such as a relief valve associated with
conduit 20 placed in series in the system.
In an alternate embodiment and to obtain a force of ejection of
liquid adapted specifically to a need, several reservoirs of the
type illustrated by reservoir 3 can be disposed in the system in
series separated by valves with controllable delivery provided by
diaphragms or lost-load devices. There is illustrated in FIG. 3
such an embodiment. In the embodiment shown in FIG. 3, several
reservoirs 3, 31 and 32 are disposed in series and are separated by
the valves 35 and 36 so arranged as to provide a controllable
delivery.
The number of reservoirs, the volume and the number of valves are
chosen by taking into account the volume of the sample to be
transferred, the viscosity thereof, its specific gravity, its
propensity for turbity and the like during the operation and at the
finish thereof. It should be evident that these characteristics are
well within the skill of the artisan to recognize and then to adapt
the device to compensate for the influence thereof.
FIG. 2 represents schematically a pipette system identical to that
illustrated in FIGS. 1a and 1b but which includes additionally a
supplementary means for permitting a sequential cleaning and drying
of the canals between each transferring operation.
To accomplish this end, the reservoir 3 is placed in communication
with a cleaning conduit 37 closed by a valve 38. Conduit 20 also
communicates with an additional conduit 21. A cleaning liquid is
adapted to enter the system via conduit 21. The entry of the
cleaning liquid into the system is controlled by valve 22. There is
also provided a valve 23 which permits the cutting off of the entry
of compressed gas 2 into the valve 7. Thus, the compressed gas is
prevented from entering the valve during the cleaning operation. In
the same manner, in order to permit conduit 40 to be cleaned, one
could dispose between the opening 722 and the valve 5, an inlet 25
for a cleaning liquid, which inlet is closed by a valve 26. The
drying of conduit 30 and reservoir 3 is effected by the compressed
gas 2. Conduit 40 is dried by connecting to it an inlet which
permits entry of a compressed gas 27. The last-mentioned inlet is
closed by valve 28.
When it is desired to dilute a transferred specimen by a calibrated
quantity of a dilution liquid, the device is modified as shown in
FIGS. 4a and 4b and two valves of the type represented by the
character 7 in FIGS. 1a and 1b, namely, valves 7 and 107 are used.
The valves 7 and 107 are connected thusly. Valve 7 is connected to
the needle 1. The receptacle 4 has disposed between it and valve 7,
the stop valve 5 and the detector 8. Valve 7 is connected to the
valve 107 by a conduit 200 having a calibrated internal volume.
Valve 7 is also connected to a depressurized draining vat 9.
Between the two is a liquid detector 90. Valve 107 is connected to
a reservoir containing a dilution liquid 110. In the path of
movement of the dilution liquid, there is disposed a valve 50
controlled by liquid detector 90. This embodiment functions as
follows:
At the start of the operation, the rotor of the valve 7 and 107
take the position represented in FIG. 4a. In this position, the
valves 5 and 50 are open. Because of the vacuum created in the
receptacle 4, the liquid to be transferred or decanted rises into
needle 1. Concurrently, the reservoir 3 fills with compressed gas.
The conduit 200 fills with the dilution liquid under the influence
of evacuating vat 9. When the liquid to be sampled reaches the
detector 8, the valve 5 closes as a result of command given by the
detector. In the same manner, when the dilution liquid reaches the
detector 90, the valve 50 is commanded to close and the aspiration
of liquid 110 ceases. Then, the rotors of valves 7 and 107 are
displaced a quarter of a turn from the position shown in FIG. 4a to
the position shown in FIG. 4b. Then, communication is established
between the needle 1 and the reservoir 3 via the conduit 200. The
pressure exerted by the gas contained in reservoir 3 causes a
predetermined measured amount of the liquid sample contained in
needle 1 and the diluting liquid contained in conduit 200 to enter
the receptacle 12. The tube 200 being calibrated and the volume of
the internal canals in valves 7 and 107 being previously measured,
one can obtain an extremely precise dilution of the sample in a
relatively rapid and feasible manner. While the aforesaid
combination of dilution and sample liquids is taking place, conduit
40 and one of the internal canals of valve 7 are in communication
with the evacuating container 9 and the residual liquids contained
therein are emptied into container 9. The apparatus is now ready to
recommence the novel sequence of operation in order to provide
another sample of the product after a rotation of a quarter of a
turn of the rotors of the valves 7 and 107 back to the position
thereof shown in FIG. 4a.
FIG. 5 represents another embodiment of the pipette system of the
present invention. It comprises a distribution valve having four
canals in the rotor and eight corresponding openings in the stator.
More generally, it should be recognized that one could utilize a
distribution sluice having n canals in the rotor and 2n openings in
the stator. The four canals are spaced equidistant from each other
about the axis of the rotor. Openings 801, 802, 803 and 804 are
respectively connected to a source of gas 2, to an expansion
reservoir 3, a hollow needle 1 and a depressurized trough 4
separated from the valve 7 by a stop valve 5 and a liquid detector
8. The four other outlets are connected in the following
manner:
Outlet 805 is connected to an inlet for a cleaning liquid, outlet
807 to an inlet for clean and dry air and outlets 806 and 808 are
for evacuation and thus are connected to an exhaust. By moving the
rotor of valve 7a through an angle of one-eighth of a complete turn
by a motor of the step-by-step type counterclockwise as shown in
FIG. 5 in the manner described above, one can perform the transfer
operation. In this new position the access of cleaning liquid and
drying air has to be prevented by respective block valves (not
shown). After the decantation of the sample liquid another
one-eighth counterclockwise turn is effected whereby canal 811 is
in a position for being cleaned, canal 813 is in a position for
being dried, canal 812 serves for pressurizing the reservoir 3, and
canal 810 connects hollow needle 1 to trough 4 for the next sample
aspiration. Thus a new operation cycle is initiated.
Although the device which has been described above in the most
preferred form for carrying out the invention, the diverse
modifications to it can be made without departing from the scope of
the present invention. Furthermore, certain elements can be
replaced by other elements capable of functioning similarly. Thus,
while there have been shown preferred embodiments of the invention,
it should be understood that the invention may be embodied
otherwise than that herein specifically illustrated and described
and that certain changes in the form and arrangement of parts and
in the specific manner of practicing the invention may be made
without departing from the underlying ideas and principles of the
invention within the scope of the appended claims.
* * * * *