Tube bottom sensing for small fluid samples

A pipetting station having a bottom sensing device is provided in conjunction with one of any known liquid level sensing devices. The bottom sensing device includes a pipetting probe spring mounted to a pipetting arm of the pipetting station. The bottom sensing device also includes a sensor for determining when a pipetting tip of the pipetting probe is in contact with a bottom of a tube. The bottom sensing device permits the pipetting probe to measure an exact volume of fluid in the tube by allowing the pipetting tip to be lowered to the bottom of the tube beyond the sensed fluid level.

BACKGROUND OF THE INVENTION
 1. Field of the Invention
 The present invention generally relates to a method and apparatus for
 sensing small fluid samples in a vessel and, more particularly, to a
 method and apparatus for determining the volume of a fluid in a vessel,
 such as a test tube, using a bottom sensing device (e.g., tip jam device).
 2. Background Description
 Analyses of fluids, especially bodily fluids such as urine and blood, are
 important to the diagnoses and treatment of various illness and other
 conditions. These illnesses and conditions can range from various forms of
 cancers to blood diseases to drug use and others.
 In order to analyze a bodily fluid, a sample of fluid is first taken from a
 person and analyzed either by hand or by an automatic analyzer or other
 device of the type well known in the art. In the case of an automatic
 analyzer, for example, the bodily fluid is disposed in a tube which, in
 turn, is disposed on a carousel or other conveying mechanism. The carousel
 or other conveying mechanism conveys the tube though scanning stations,
 for example, and under a pipetting station in order for a pipetting probe
 to aspirate a sample of the fluid.
 The pipetting probe is then lowered into the tube in order to aspirate a
 sample of the fluid. Thereafter, and depending on the specific test or
 tests to be performed on the fluid, a specific reagent may be combined
 with the fluid in order for a chemical reaction to occur. This chemical
 reaction is then analyzed to determine, for example, the amount of analyte
 in a sample of fluid.
 It is not uncommon for many different tests to be performed on the sample
 fluid using different reagents. However, in order for the appropriate
 tests to be performed on the sample fluid a sufficient amount of the
 sample fluid must be present in the tube. Accordingly, when using
 automatic analyzers, the sample level in the tube is normally determined
 by the pipette probe which is connected to a sample sensing means such as
 a capacitive or conductive circuit. The sensing means is triggered upon
 contact of the pipette tip with the surface of the sample. The pipette
 probe is then further lowered a distance into the sample sufficient to
 allow withdrawal of the required volume. However, to ensure that an
 insufficient volume of sample will not be drawn, owing to the sample level
 being too close to the bottom of the tube, the pipette tip will only be
 allowed to be lowered to a certain level within the tube resulting in a
 volume of sample, called the dead volume, that is unavailable for testing.
 The maximal distance the pipette tip is allowed to be lowered, and thus
 the nominal dead volume, is set by the manufacturer of the automatic
 analyzer It is noted that the actual dead volume is variable and is
 dependent on several dimensional tolerances that exist within and between
 different instruments. A more dimensionally precise automatic analyzer
 would allow the pipette tip to aspirate fluids at a lower level than other
 less precise automatic analyzers, and thereby allow the manufacturer to
 set a smaller sample dead volume. Any amount of sample fluid below the
 preset dead volume level can not be utilized to perform a test or tests
 thereon despite the fact that the fluid in the test tube below the dead
 volume level may still be sufficient to perform a test or tests thereon.
 Thus, what is needed is a system that determines the exact volume of a
 fluid below a threshold level which may be defined as a near bottom tube
 level. It is noted that the near bottom tube level is an arbitrary level
 of fluid in the tube, and may be predefined by the manufacturer of an
 automatic analyzer. The determination of the exact volume of a fluid in
 the tube will allow the automatic analyzer or other device to determine
 whether there is a sufficient amount of fluid in the tube in order to
 perform a certain predetermined test or tests.
 SUMMARY OF THE INVENTION
 It is therefore an object of the present invention to provide a system and
 method for determining a bottom of a tube or other container.
 It is a further object of the present invention to provide a system and
 method for determining the volume of a fluid in a tube or other container.
 It is also an object of the present invention to provide a system and
 method of measuring a reagent in a reagent container.
 It is still another object of the present invention to provide a system and
 method for determining whether a sufficient amount of fluid is present in
 a tube for a specific test or tests.
 In order to accomplish the objects of the present invention, a pipetting
 station having a bottom sensing device is provided in conjunction with one
 of any known liquid level sensing devices. The bottom sensing device
 includes a pipetting probe spring mounted to a pipetting arm of the
 pipetting station. The bottom sensing device also includes a sensor for
 determining when a pipetting tip of the pipetting probe is in contact with
 a bottom of a tube.
 The bottom sensing device of the present invention permits the pipetting
 probe to measure the volume of fluid in the tube by allowing the pipetting
 tip to be lowered to the bottom of the tube beyond the sensed fluid level
 (and the near bottom tube level). In the embodiments of the present
 invention, the pipetting arm is further lowered until the pipetting probe
 triggers a sensor which stops the downward movement of the pipetting arm.
 The exact distance between actual tip jam and triggering of the tip jam
 sensor, and therefore the actual bottom of the tube, is known and
 configured for each instrument.
 A determination is then made as to (i) an exact volume of fluid and (ii)
 whether there is sufficient sample fluid in the tube to perform a test or
 tests thereon. The determination of the volume of fluid in the tube is
 based on (i) the sensed level of the fluid as determined by the level
 sensor (in relation to a "home" position of the pipetting arm), (ii) the
 distance the pipetting arm traveled from the level of the sample fluid to
 the time when the pipette tip contacts the bottom of the tube and (iii)
 the type of tube used for holding the fluid. If sufficient fluid is
 present, then the pipetting tip is raised slightly above the known tube
 bottom level in order to aspirate sample fluid or reagent therefrom.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION
 The present invention is directed to a method and apparatus for sensing
 fluids of small samples in a tube and, more specifically, to a method and
 apparatus for determining the volume of a fluid in a tube that is below a
 near bottom tube level using a bottom sensing device. The bottom sensing
 device is used to determine the volume of a fluid in a tube, as described
 in detail below. By using the apparatus and method of the present
 invention, a pipetting station of an automatic analyzer or other device
 may aspirate fluids of small samples for testing thereon.
 In order to accomplish the objectives of the present invention, a bottom
 sensing device is implemented in conjunction with a pipetting tip having a
 capacitive level sensor or other means of sensing fluid levels. A
 pipetting capacitive level sensor contemplated for use with the present
 invention is disclosed in U.S. Pat. No. 5,648,727 and is incorporated
 herein by reference in its entirety. In general, the capacitive level
 sensor disclosed in U.S. Pat. No. 5,648,727 includes a pipetting probe
 having an elongated shaft having a conductive tip, and an integrated
 circuit chip containing a capacitive sensing circuitry. When the
 conductive tip is lowered and contacts a sample fluid, an increase in
 capacitance is sensed. This sensed increase in capacitance is used to
 determine the level of the sample fluid in relation to a "home" position
 of the pipetting arm. It is well understood that other level sensors may
 also be used with the present invention, such as, for example,
 electrically conductive sensors or air pressure sensors.
 The bottom sensing device includes a spring loaded pipetting arm having a
 sensor which senses when the pipetting tip is in contact with the bottom
 of the tube. It is noted that the automatic analyzer or other device does
 not identify that the pipetting tip is in contact with the bottom of the
 tube until after the sensor is triggered. Accordingly, the automatic
 analyzer or other device identifies the bottom of the tube when the spring
 loaded pipetting arm travels until the sensor is "flagged" (e.g.,
 triggered). The distance between the actual tube bottom and the triggering
 of the sensor is a known configured number of steps on a stepper motor. In
 a preferred embodiment, the triggering of the sensor will stop the
 downward movement of the pipetting arm.
 In the preferred embodiments, once the pipetting arm is raised or during
 raising thereof, a determination may be made as to (i) the volume of fluid
 and (ii) whether there is sufficient sample fluid in the tube to perform a
 test or tests thereon. The determination of the volume of fluid in the
 tube is based on, in part, (i) the distance the pipetting arm traveled
 from the level of the sample fluid to the time when the sensor was
 triggered minus the certain distance traveled after the pipetting tip is
 in contact with the bottom of the tube and (ii) the known shape of the
 type of tube used to hold a sample fluid. FIGS. 3a-3c show a detailed view
 of the pipetting station using the bottom sensing device of the present
 invention, and FIGS. 5 and 6 show a detailed flow diagram explaining a
 process used with the bottom sensing device of the present invention.
 In order to practice the present invention, an automatic analyzer or other
 known device is needed to perform the specific tests on the fluid samples.
 In general, FIG. 1 shows a block diagram of an automatic analyzer which
 may be used with the present invention. The automatic analyzer 10 is
 connected to a computer 12 via data communication lines 14 which are used
 to supply information from the automatic analyzer 10 to the computer 12.
 This information may be, for example, bar coded information placed on the
 sample fluid tubes. The automatic analyzer 10 is preferably operated under
 the direction of onboard microprocessors (not shown). It is well
 understood that the block diagram of FIG. 1 is not critical to the
 understanding of the present invention and that other devices depicted in
 other block diagrams may equally be used with the present invention,
 including non-medical devices.
 FIG. 2 shows a partial view of the automatic analyzer 10 in greater detail.
 It is noted that the automatic analyzer 10 of FIG. 2 is an IMMULITE
 2000.TM. manufactured by DPC.RTM. Cirrus (a subsidiary of Diagnostic
 Products Corporation) of Randolph, New Jersey; however, it is noted that
 the automatic analyzer of FIG. 2 is merely representative of one automatic
 analyzer used with the present invention and it is well understood that
 the present invention may easily be implemented with other automatic
 analyzers or other fluid sample devices known to one of ordinary skill in
 the art. It is further important to note that the automatic analyzer of
 FIG. 2 is merely described herein for illustrative purposes and to better
 understand the present invention, and that only the bottom sensing device
 of the pipetting station and the method of use discussed herein (with
 reference to FIGS. 3a-6) are part of the present invention.
 Referring more specifically now to FIG. 2, a sample carrier tube 20 is
 transported by a carousel 22 towards a reagent pipetting station 24 and
 sample pipetting station 24A. Prior to being transported to the pipetting
 stations 24 or 24A, the sample carrier tube 20 may be transported through
 a bar code reader 26. In the embodiments of the present invention, the bar
 code reader 26 may identify the person (of which the sample fluid belongs
 to) or type of tube being used such as, for example, a pediatrics or micro
 sample tube. In the case of a pediatrics or micro sample tube, the
 computer of FIG. 1 will include an alternative look-up table in order to
 calculate the volume of the fluid in the sample, as discussed below.
 It is noted that the information from the bar code reader 26 is sent to the
 memory of the computer 12, which may also track the position of the sample
 carrier tube 20 on the carousel 22. It is further noted that the computer
 may be preprogrammed to include the volume table of known volumes of tubes
 (such as conical bottom tubes and micro sample tubes) as well as the
 volume of fluid needed to perform a certain test or tests on the fluid.
 The computer may also be programmed to prioritize which tests may be
 performed with the amount of fluid present in the tube. For example, if
 three tests must be performed on the fluid, the system and method of the
 present invention may prioritize that the first and third test be
 performed to the exclusion of the second test since only enough sample
 fluid is present in the tube to perform the first and third test. Of
 course other variations may also be provided for by the present invention.
 As seen further in FIG. 2, the reagent pipetting station 24 and sample
 pipetting station 24A include a reagent pipetting arm 32 and a sample
 pipetting arm 32A, respectively, which both may travel a circular path.
 (Hereinafter, the reagent pipetting station 24 and sample pipetting
 station 24A are referred to as the pipetting station 24 and the reagent
 pipetting arm 32 and sample pipetting arm 32A are referred to as the
 pipetting arm 32.) In this path, the pipetting arm 32 may extend to the
 sample carrier tube 20 in the carousel 22, a reagent 28 in the reagent
 carousel 40, and a probe wash station 30. The pipetting arm 32 may also
 travel in other paths, and may equally extend to other carriers or
 stations, such as for example, a sample dilution well 31. A downward
 projecting pipetting tip (shown in FIGS. 3a-3c) is positioned at the free
 end of the pipetting arm 32. To perform pipetting operations, the
 pipetting tip is inserted into and out of the sample carrier tubes 20 and
 other stations along its Z-axis (perpendicular to the plane of the paper).
 Referring now to FIG. 3a, a detailed view of the pipetting station in a
 "home" position is shown. The pipetting station 24 includes the pipetting
 arm 32 that moves in the direction of arrow 42, and a pipetting probe 34
 spring mounted to the pipetting arm 32 of the pipetting station 24. The
 pipetting probe 34 includes a pipetting tip 36 having a capacitive level
 sensor as described with reference to U.S. Pat. No. 5,648,727. The
 capacitive sensor senses a level of the fluid and determines that level in
 relation to a known "home" position. The tube 20 is placed in a holding
 device (see FIG. 4) so that a bottom of the tube 20 is at the reference
 line "X" which is used as a reference point for discussion purposes only.
 The bottom sensing device of the present invention includes a spring
 mechanism 38 and a sensor 40 mounted between the pipetting probe 34 and
 the pipetting arm 32. Specifically, the spring mechanism 38 is mounted to
 the pipetting probe 34 in the pipetting arm 32 and permits the pipetting
 arm 32 to work independently of the pipetting probe 34 as seen more
 clearly with reference to FIG. 3b and FIG. 3c. In general, the pipetting
 arm 32 lowers the pipetting probe 34 until the pipetting tip 36 is in
 contact with the bottom of the tube 20 (past a near bottom tube level)
 (FIG. 3b). The pipetting arm 32 is then further capable of being lowered
 an incremental distance while the pipetting probe 34 remains stationary
 and the pipetting tip 36 is in contact with the bottom of the tube 20
 (FIG. 3c).
 The sensor 40, preferably positioned proximate the pipetting arm 32,
 determines when the pipetting arm 32 has traveled the incremental
 distance, such as, for example, approximately in the range of 1 mm to 4 mm
 or more, while the pipetting probe 34 remains stationary (represented as
 "Z" distance in FIGS. 3b and 3c). It is noted that the bottom sensing
 device of the present invention determines that the pipetting tip 36 is in
 contact with the bottom of the tube 20 when the sensor 40 is triggered, at
 which time the downward movement of the pipetting arm 32 is stopped, and
 in embodiments the pipetting tip 36 may be raised an incremental amount
 within the fluid so that pipetting tip 36 will not become occluded when
 aspiration of the fluid begins.
 FIG. 3b shows the pipetting probe 34 in a lowered position and the
 pipetting tip 36 in contact with the bottom of the tube 20. As seen with
 reference to the line "X", the tube 20 remains stationary throughout the
 process while the pipetting arm 32 and pipetting probe 34 are lowered. It
 is readily apparent that the pipetting arm 32 and the pipetting probe 34
 are synchronously lowered until the pipetting tip 36 is in contact with
 the bottom of the tube 20.
 FIG. 3c shows the pipetting arm 32 being lowered an incremental distance
 "Z" while the pipetting probe 34 is stationary and the pipetting tip 36 is
 in contact with the bottom of the tube. At this stage the sensor 40 is
 activated after the pipetting arm has been lowered the incremental
 distance "Z". The independent movement of the pipetting arm 32 with
 relation to the pipetting probe 34 is due to the spring loaded mechanism
 38 described with reference to FIG. 3a. It is noted that the incremental
 distance between the actual bottom of the tube and the triggering of the
 sensor of the pipetting arm 32 is configured for each individual pipetting
 station 24 such that the traveled distance may vary between different
 pipetting stations.
 Thus, by using the bottom sensing device of the present invention, the
 pipetting tip 36 can be lowered past the level of the fluid and the volume
 measurement of the fluid in the tube 20 can be determined. This is
 provided by the use of the spring loaded mechanism 38 in conjunction with
 the independent movement of the pipetting arm 32 and the activation of the
 sensor 40 as discussed with reference to FIGS. 3a-3c. Once the volume of
 fluid is known, the system of the present invention can determine whether
 a sufficient amount of fluid remains in the tube 20 in order to perform a
 certain predefined test. The volume of the sample fluid in the tube 20 is
 calculated by (i) a known volume based on a type of tube used to hold a
 sample fluid, (ii) a top level of the sample fluid in the tube as sensed
 by the level sensor, and (iii) a distance of movement of the pipetting arm
 minus the certain distance the pipetting arm traveled after the pipetting
 tip is in contact with the bottom of the tube. Alternatively, the present
 invention can prioritize between which tests are to be performed on the
 fluid, as discussed above.
 FIG. 4 shows a comparison between a standard tube (having a rounded bottom)
 and a conical bottom tube in a tube holding device. Specifically, the
 standard tube is held in the tube holding device 42 by use of a resilient
 spring 44 biasing the standard tube against a wall 47 of an opining 45. At
 a bottom of the tube holding device 42 is an opening 46. The opening 46 is
 configured such that the bottom of the standard test tube remains at the
 reference line "X" as discussed with reference to FIGS. 3a-3c. However,
 the opening 46 allows the bottom of the conical shape tube to exceed
 beyond the reference line "X" to reference line "Y". In the preferred
 embodiment, the distance between the reference line "X" and the reference
 line "Y" is about 0.10 inches; however, it is well understood that any
 other distance may also be contemplated for use with the present
 invention. As discussed in more detail with reference to FIGS. 5 and 6,
 the pipetting tip may be lowered past the reference line "X" (step S58a)
 to reference line "Y" such that the system of the present invention will
 automatically identify that a conical shaped bottom tube is being used
 with the present invention. In this case, when the system of the present
 invention automatically identifies that such a conical shaped bottom tube
 is being used, the sample volume of the tube will be calculated by
 reference to an alterative look-up table which is different from the
 look-up table for the standard tube.
 Prior to discussing FIGS. 5 and 6, it is noted that the calculation of the
 volume of the fluid in the tube is calculated by the CPU of the computer
 or other similar device. It is also readily understood by one of ordinary
 skill in the art that all other calculations and determinations discussed
 herein are also calculated by the CPU of the computer or other similar
 device. These calculations and determinations may further include the
 prioritization of the tests being performed on the fluid as well as the
 near tube bottom position (e.g., the position of prior art systems in
 which one was assured that there was enough fluid to run a specific test
 or tests).
 More specifically, the invention can be implemented using a plurality of
 separate dedicated or programmable integrated or other electronic circuits
 or devices (e.g., hardwired electronic or logic circuits such as discrete
 element circuits, or programmable logic devices such as PLDs, PLAs, s,
 or the like). A suitably programmed general purpose computer, e.g., a
 microprocessor, microcontroller or other processor device (CPU or MPU),
 either alone or in conjunction with one or more peripheral (e.g.,
 integrated circuit) data and signal processing devices can be used to
 implement the invention. In general, any device or assembly of devices on
 which a finite state machine capable of implementing the flow charts shown
 in FIGS. 5 and 6 can be used as a controller with the invention.
 FIG. 5 is a flow diagram showing the process of using the bottom sensing
 device of the present invention. Specifically, at step S40, a "home
 position" is determined and stored in the memory of the computer. At step
 S42, the pipetting arm is lowered and, at step S44, a determination is
 made as to whether any fluid is sensed at or above a near tube bottom
 level position, typically 250 .mu.l or other determined level. If fluid is
 sensed at the near bottom tube level position, at step S46, a sample of
 the fluid is aspirated into the pipetting probe and a test is performed
 thereon. However, if no fluid is sensed at the near bottom tube level
 position, at step 48, the pipetting arm is lowered until a fluid level is
 sensed. At this step, it is preferred that the lowering of the pipetting
 arm be slower than the previous movement of the pipetting arm to ensure
 that the pipetting tip does not contact the bottom of the tube at such a
 rate of speed as to damage or destroy the tube or pipetting tip or arm.
 At step S50, a determination is made as to whether the pipetting tip is in
 contact with the bottom (discussed in detail below) of the tube fluid
 prior to sensing any fluid within the tube. If no fluid is sensed, a
 determination is made that there is no fluid in the tube and the process
 of the present invention stops, at step S52. However, if a fluid is
 sensed, at step S54, a position reading of the pipetting arm (or probe or
 tip) with relation to a "home" position is determined and stored in the
 memory of the computer. The position reading is determinative of the level
 of sensed fluid.
 At step S56, the pipetting tip is lowered until it is in contact with the
 bottom of the tube. As discussed above, the pipetting station does not
 know that the pipetting tip is in contact with the bottom of the tube at
 this step. Thus, in order to determine that the pipetting tip is in
 contact with the tube, at step S58, the pipetting arm is lowered an
 incremental distance while the pipetting probe remains stationary until
 the sensor is triggered. Once the sensor is triggered at step S58, the
 downward movement of the pipetting arm is stopped. At step S60, the
 pipetting arm and pipetting probe may be raised an incremental amount
 within the fluid, preferably just above the known tube bottom level, so
 that the pipetting tip 36 will not become occluded when the fluid is
 aspirated by the pipetting probe. It is at this step S58, that the
 pipetting station knows that the pipetting tip is in contact with the
 bottom of the tube and may thus determine the volume of fluid present in
 the tube.
 In an alternate embodiment, the pipetting tip may be lowered past the
 reference line "X" (step S58a) by a certain distance such that the system
 of the present invention will identify that a conical shaped bottom tube
 is being used with the present invention. This is based on the fact that
 the conical shaped tube, in the embodiments of the present invention,
 preferably extend past the reference line "X" so that when the pipetting
 tip passes the reference line "X" the system of the present invention will
 automatically identify that such a conical shaped bottom tube is being
 used herein. In this case, the sample volume will be calculated by
 reference to an alterative look-up table which is different from the
 look-up table for a standard tube.
 At step S62, the volume of fluid in the tube is determined (as described
 above with reference to FIG. 3a). That is, the volume of the tube is
 calculated by using a look-up table for the tube and by(i) a known shape
 of the type of tube used to hold a sample fluid, (ii) a top level of the
 sample fluid in the tube as sensed by the liquid level sensor, and (iii) a
 distance of movement of the pipetting arm minus the certain distance the
 pipetting arm traveled after the pipetting tip is in contact with the
 bottom of the tube.
 At step S66, a determination is made as to whether there is sufficient
 amount of fluid in the tube to perform desired specific tests. If there is
 not a sufficient amount of fluid, then the process of the present ends at
 step S68. However, if there is enough fluid present in the tube, then at
 step S70, the present system may prioritize which tests may be performed
 on the fluid sample and being aspiration of the fluid for testing thereon.
 Alternatively, the operator can be alerted that insufficient sample is
 available to complete all of the required tests, and the operator can then
 select manually which test or tests may be performed on the sample fluid.
 As discussed above, a known volume table for tubes is provided to the
 system of the present invention. This allows the present invention to
 "look up" an appropriate table in order to calculate the volume of the
 tube based on the movement of the pipetting arm with relation to a sensed
 level of the fluid and a determined bottom position of the tube. It is
 also readily understood by one of ordinary skill in the art that the
 system of the present invention also stores in memory or the like the
 amount of fluid needed for the specific test or tests.
 FIG. 6 is a flow diagram showing an alternative process of using the bottom
 sensing device of the present invention. In this embodiment, the sample
 tube is a conical or a round bottom micro tube which is contained in a
 special bar coded insert or rack. In the case of the micro tube (and in
 embodiments the conical bottom tube), an identification is provided by a
 second interrogation of the sample carousel or conveyer by the bar code
 reading station. The preconfigured new tube bottom position based on the
 detected tubes would be different from each of these tubes as well as
 being different from the standard tube. It is further noted that each tube
 has its own look-up table such that the sample volume of each different
 tube may be calculated by reference to a specific look-up table.
 More specifically, after step S40, the tube is passed by a bar code scanner
 for reading of a bar code (step S41a). This step may also be performed
 prior to step S40. The bar code reader provides the bar code information
 to the computer such as, but not limited to, (i) the type of tube being
 used to hold the fluid and (iii) the identifying information of the fluid
 (e.g., person). In this embodiment of the present invention, the system of
 the present invention may also consult a look up table to determine the
 amount of fluid needed for a specific test or tests to be performed on the
 fluid. The remaining steps of FIG. 5 may then be implemented.
 It is noted that when using the conical bottom tube, the system of the
 present invention will automatically identify such a conical bottom tube
 when the pipetting tip exceeds the reference line "X" at step S56.
 While the invention has been described in terms of a single preferred
 embodiment, those skilled in the art will recognize that the invention can
 be practiced with modification within the spirit and scope of the appended
 claims.