Abstract:
Automated laboratory apparatus for determining the volume of liquid samples contained in the cavities of laboratory sample collectors, such as well trays or tube racks, the apparatus having an ultrasonic height measuring instrument and a processor for calculating the volume of liquid in a particular sample container from the measured height, the apparatus also having a robotic displacement mechanism that selectively positions an ultrasonic height measuring sensor above a select sample container in the well tray or tube rack for measuring the height of liquid in the container, comparing the measured height to the height of the bottom of an empty container and calculating the volume of liquid in that container.

Description:
RELATED APPLICATION 
   This application claims the benefit of U.S. Provisional Application Ser. No. 60/762,928, of the same title, filed Jan. 27, 2006. 

   BACKGROUND OF THE INVENTION 
   This invention relates to laboratory apparatus for the automated measuring of the volume of liquid in sample containers arranged in sets, such as sample tubes in tube racks and sample wells in well trays. In particular, the apparatus utilizes an ultrasonic sensor to detect the height of liquid in a tube cavity or well cavity and determine the volume from an algorithm that calculates the volume from the shape of the cavity and the height of the liquid surface from the bottom of the cavity. The automated measuring apparatus includes optional auxiliary sensors, such as a camera, to visually inspect and record the status of a cavity or the identity of a sample or samples from a marking adjacent the cavity or on a surface covering the cavity. 
   A primary object of this invention is to create an automated measuring device for a variety of laboratory containers for the purpose of quality assurance, sample management and other purposes. 
   The method of this invention is to take the automated measurement of the volume of various laboratory racks and plates or other grouped containers by use of an ultrasonic transducer being passed over the associated cavity position to measure the height of matter in the cavity which would then be interpolated to indicate the volume of the material in the particular cavity. 
   While typical laboratory racks and plates or other sets of grouped containers are frequently positioned based on standard spacing, there is no requirement that they be so spaced for the automated measuring system of this invention. Many standard plates and racks are based on a matrix of 98 or 384 wells or tubes. Non standard or random spacing could be addressed by the invented device as well by appropriate programming. 
   This device would provide an accurate method of collecting interpolated volume data in a rapid fashion. 
   Other methods currently in use to establish volumes and or weights of tubes or racks containing tubes or containers are to weigh each associated tube or container. Assuming that the tube had been previously tare weighted, the weight of the contents could be determined. However, with laboratory well plates or trays there is no easy solution. The wells are customarily formed as part of the plate and do not have removable containers. As such, individual cavities cannot be removed to be measured for volume or weight. The automated measuring device of this invention solves this problem by measuring the liquid level in the cavity. 
   SUMMARY OF THE INVENTION 
   The ultrasonic height and volume measuring instrument of this invention is an automated laboratory apparatus for determining the volume of liquid samples contained in the cavities of laboratory sample collectors, such as well trays or tube racks. In addition, the automated laboratory apparatus optionally includes an imaging device, such as a digital camera, to capture an image of the contents of a cavity or a marking on or adjacent to a cavity. The imaging device can also capture a marking, such as a bar code, on the sample container to identify the rack or tray or determine the orientation of the rack or tray. 
   There are two typical operations required to accurately determine the volume of material in a particular well cavity. First, is to establish the height measurement of each empty well cavity. Then, measure the same well cavity after the material is placed into the well cavity. This will establish the physical vertical dimension of the liquid. For volume, it would be necessary to use a calculation factor established for each type of cavity to be measured since the cavities are usually not constructed of parallel sides and flat bottoms, but rather of some variation of a conical shape. The same procedure can be applied to test tubes in a rack. 
   Mechanically, to measure the individual containers in a rack or tray, the rack or tray would be placed in a fixture on a support carrier. Upon electronic signal, the carrier would retract into the machine to align a sensor over the first row. The sensor would travel transversely over the row, taking height measurements over each of the cavities. Once the row is complete, the support carrier would further retract into the machine and the sensor would again travel over the next row, taking the next set of measurements and so on until all rows would have been measured. Once all measurements have been completed, the support carrier will fully extend for removal of the rack or tray. The measurements could be taken in the retraction motion, extension motion, or a combination of both. 
   The particular methodology described is only one example as the sequence of measurement can be programmed for any specified pattern. For instance, instead of addressing rows, the device could be configured to address the columns at right angle to the rows or any other regular or random sequence that the user required. 
   Multiple passes for confirming minimum heights may be desirably to avoid a false reading which could, for example, be caused by a drop on the side of a container and not the actual bottom of the cavity. These passes might be in a predetermined pattern or could be deliberately set to be random for quality assurance purposes. 
   Possible modes:
         X direction of or Y direction only;   XYZ combination;   Bi-directional; and,   Multiple sensors for increased speed or other uses.       

   Sensors may detect:
         The presence of a rack or tray;   Proper insertion of the rack or tray; and,   Bar code and/or RFID reader for the rack or tray.       

   Applications:
         Automated measuring of heights and volumes in cavities;   Automated checking for caps and cap insertion; and,   Other detection operations such as the absence of a tube in a tube rack.       

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
       FIG. 1  is a perspective view of the ultrasonic test instrument. 
       FIG. 2  is a perspective view of the ultrasonic test instrument of  FIG. 1  with the housing removed. 
       FIG. 3  is a partial side view of the ultrasonic test instrument of  FIG. 2  with an added digital camera. 
   

   DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
   Referring to  FIG. 1 , the ultrasonic test instrument is designated by reference numeral  10  and is shown as a compact desktop device with a standard tube rack  12  holding a plurality of test tubes  14  some of which have tube caps  16 . The test instrument  10  is preferably designed to operate with a conventional personal computer  18  that functions as a convenient input and output device. When programmed with an application program, the computer carries out the desired operations and records the necessary data for use. It is to be understood that with the addition of an appropriate conventional display control panel and internal processor, the test instrument can be a stand-alone device. 
   The test instrument  10  has a housing  20  providing a protective enclosure with a front  22  having an opening  24  with an extendable and retractable platform carrier  26  adapted to seat a tube rack  12 , as shown, or a typical well tray (not shown). The rack  12  is positioned on the platform carrier  26  by retainer pegs  28  which are located in selected positioning holes  30  for the particular multi-cavity sample collector, such as a tube rack or well tray. 
   On the front  22  of the housing  20  are basic control switches  32  and indicator lamps  34  for “on” and “operating.” The housing front  22  has a sloped portion  36  that provides a convenient mounting surface for other operating controls and displays for a stand-alone device as noted. 
   Referring to  FIG. 2 , the test instrument  10  is shown with the housing  20  removed. The test instrument is constructed with a frame  36  having a back wall  38 , a support bed or deck  40  and a front bridge structure  42 . On the back wall  38  is a controller  44  that manages the operation of the instrument  10  and controls the data collection from an ultrasonic sensor  46  through an electronic connecting cable  50 . The ultrasonic sensor  46  is seated in a holder  48  displaceably supported on a track  52  mounted to a cross member  54  of the bridge structure  42 . The holder  48  has a bracket  56  with a slide  58  that engages the track  52  and an arm  60  that is connected to a belt  62  of a belt drive  64 . The belt drive  64  has a drive motor  66  and guide spools  68  mounted to the vertical members  70  of the bridge structure  42  for transporting the ultrasonic sensor  46  back and forth across the cross member  54  under command of the controller  44 . 
   The deck  40  is supported at one end by the back wall  38  and at the other end by the bridge structure  42 . The deck  40  projects through an opening  72  in the bridge structure  42  and supports a carriage rail  74  on which the platform carrier  26  is slidably supported. 
   The platform carrier  26  has a bracket  76  fastened to the carrier  26  with an arm  78  connected to a belt  80  of a belt drive  82 . The belt drive  82  has a drive motor  84  and guide spools  86  mounted to the deck  40  for transporting the platform carrier  26  forward and aft over the deck  40  and allowing the carrier  36  to be extended outside of the housing  20  as shown in  FIG. 1 . Appropriate sensors  87  (one shown) limit displacement and provide a reference point for calculating the position of the ultrasonic sensor  46  during operation. Typically, before operation all tube caps  16  are removed and a sequence of measurement is selected. 
   During operation, the power supply  88  is activated and the controller  44 , under command of the associated computer  18 , displaces the support carrier  26  fore and aft over the deck  40  and displaces the ultrasonic sensor  46  back and forth across the track  52  on the cross member  54  of the bridge structure. In this manner, the sensor can be selectively positioned over any and all tubes in a tube rack or wells in a well tray mounted on the support carrier  26 . When appropriately positioned, the controller activates the sensor and retrieves a reading that is processed to provide a calculated volume of liquid in the measured container. This information is further processed and/or recorded as required by the user. 
   As noted in this specification, the cavities for the removable tubes contained in the rack or the fixed wells in the well plates or trays are not cylindrical, but usually have sloped sides and flat or rounded bottoms. However, the liquid volume can easily be calculated from an algorithm defining the cavity with surface height as the variable that is measured by the sensor. Greater accuracy is naturally provided by measuring each cavity when empty and subsequently measuring the cavities when filled. However, the cavities are typically uniform and, given the known or sensed depth of one cavity, the liquid height and, hence, volume can be determined by sensing the liquid level in the set of cavities of a given tube rack or well tray seated in the measuring device. 
   The measuring device can also be used for other operations, such as the automated check for caps, and for proper cap insertion as well as the absence of a tube or tubes in a rack. 
   In addition to the primary test for liquid volume in the tubes in a tube rack or wells in a well tray, the measuring device can be equipped with an auxiliary sensor to capture an image of each tube or well. 
   As shown in the partial side view of  FIG. 3 , the front bridge structure  42  supports the ultrasonic sensor holder  48  on a horizontal track  52  by a keyed slide  58 . The slide  58  and sensor holder  48  are transported by the bracket  56  sandwiched between the slide  58  and holder  48 . The bracket  56  has an extending arm  60  that is fastened to the belt  62  by a clamp  90 . In this manner, the sensor holder  48  can be transported back and forth along the track  52  by the drive motor  66 . 
   As shown in  FIG. 3 , by mounting a digital camera  92  in a camera bracket  94  fastened to the ultrasonic sensor holder  48 , the same transport apparatus is utilized to move the camera  92  back and forth along the same track  52 . The digital camera  92  is preferably a small CCD camera with an accompanying operating circuit board  94  that cooperates with the controller  44 , and any additional processing circuitry on a board  96  under the deck  40 . The control feedback and imaging data are transmitted through the cable  98  which electronically connects to the controller  44  and board  94 . 
   Preferably, transport control for the digital camera  92  in both the X and Y directions is independent of the ultrasonic sensor  46  and utilizes a similar search and mapping routine to establish the size, number and layout of the tubes in a tube rack or cavities in a well tray. In a dedicated system that only operates for a specific size rack with a specific number of tubes, for example, the transport protocol can be combined with a known one row off-set for the camera with relation to the ultrasonic sensor by appropriate relative positioning of the camera and ultrasonic sensor. 
   The addition of the camera expands the capability of the system which can be varied by the software application programs typically processed in the auxiliary computer  18 . For example, the camera can check any tube that the ultrasonic sensor detected having a cap or check a location the sensor detected to be empty. The camera can be used with a bar code processing program to identify tubes with bar code marked caps or identify bar code markings on racks or well trays. Additionally, the camera can be used as a visual verification of the contents of a tube or well cavity with the image stored for visual reference in association with the volumetric content of cavities. 
   The software application program is designed for user customization to tailor the automated operations with the laboratory procedures being implemented. The application program includes the customary data storage, visual display and reporting capabilities, typically required in managing multiple tube and well processing systems. 
   As previously noted, with a programmable procedure, the transport protocol can be varied by the operator with the sensors stopping at each cavity in a row before the platform is incrementally moved in or out or in a custom pattern devised by the operator. 
   While in the foregoing, embodiments of the present invention have been set forth in considerable detail for the purposes of making a complete disclosure of the invention, it may be apparent to those of skill in the art that numerous changes may be made in such detail without departing from the spirit and principles of the invention.