Abstract:
An automated weighing station is provided which is advantageous for automatically weighing samples generally disposed in containers in an array of racks. The weighing station comprises a sample handling assembly which is operably connected to a balance, allowing a moveable sample carrier to bring samples into position beneath the balance and sample handling assembly, thereby minimizing the movement of individual samples in order to accomplish weighing. A weighing system that provides flexibility and convenience in generating and transforming a variety of data sets associated with measurements accomplished using the weighing apparatus is also provided.

Description:
FIELD OF THE INVENTION 
     The present invention relates to a weighing apparatus. An embodiment of the present invention is advantageous for automatically weighing small samples generally disposed in containers in an array of racks. The invention also relates to weighing systems that provide flexibility and convenience in generating and transforming a variety of data sets associated with measurements accomplished using the weighing apparatus. 
     BACKGROUND 
     Recently, the proliferation of combinatorial libraries in high throughput synthesis and screening (HTS) programs have led to an ever increasing emphasis on automation. The ability to prepare and test a large number of compounds quickly can provide a competitive advantage. Thus, automated preparation and evaluation has become a key process in lead discovery. 
     The recent explosion in the number of compounds available for screening, and the expected increase in compounds with the development of automated chemical synthesis, has meant that a large number of pharmaceutical and other chemical companies are in need of automated weighing of such compounds. However, several difficulties have been encountered in attempts to provide a fast, efficient, and cost-effective solution to the problem of automatically weighing large numbers of small samples. 
     Proposed solutions which simply implement robotic methods to remove and replace samples from racks to facilitate weighing present significant problems. Robotic fingers have difficulty in grasping individual samples for removal from among an array of closely placed samples in a rack. Certain devices function only with flat bottom containers, which are more difficult to return to the rack after weighing. Misplacement during return may result in spilling of the sample contents, or breakage of one or more samples (possible leading to contamination of on e or more samples). 
     A major difficulty unsolved by current devices is the lack of speed when weighing a large number of samples. Current devices generally employ a robotic sample transfer assembly, which retrieves a sample from an array, transfers the sample to a separate balance, and then returns the sample container to a particular position in a holder, such as a test tube rack. Although some such systems may have the ability to identify the particular sample, and associate the sample with the measurement taken to enable later data recordation and processing, systems currently employed require a large amount of inefficient and time-consuming movement. The sample must be plucked from an array, moved to the balance, retrieved from the balance, moved back into position relative to the array, and returned to the sample&#39;s original position. Thus, having the balance a considerable distance from the actual sample position within an array leads to a great deal lost time in moving each sample to and from the balance. 
     Current devices also handle a relatively limited number of samples during each run. It would be advantageous to provide an automated system which is capable of handling a larger number of samples than those devices currently available. 
     Accordingly, it is one object of the present invention to provide an automated weighing system which handles a larger number of samples per run than currently available devices. It is also an objection of the invention to accomplish weighing of a large number of samples in less time, and with increased handling efficiency and reliability. Additionally, another object of the invention is to provide a weighing system allowing increased control of an automated weighing apparatus, and increased versatility in data collection, storage and transformation. 
     SUMMARY OF THE INVENTION 
     The present invention provides a solution to many current problems associated with automated weighing of large numbers of samples. One advantage is that the overall movement of individual samples to accomplish the weight measurement is minimized. This reduces the time required, and reduces the likelihood of malfunctions such as breakage of sample containers and/or contamination of samples. 
     Accordingly, in one aspect the invention relates to an automated weighing station comprising a support frame, a balance secured to the support frame, a sample handling assembly operably connected to the balance and secured to the balance, a moveable carrier for moving samples into position beneath the sample handling assembly, a lift assembly positioned beneath the moveable carrier and the sample handling assembly for lifting samples into position to be accessed by the sample handling assembly, and a control system for controlling the sample handling assembly, the lift assembly, and the moveable carrier in a coordinated manner, and for storing weight measurements of individual samples. The control system also provide a user interface. 
     In another aspect, the invention relates to a method of weighing multiple individual samples comprising moving an ordered array of sample containers beneath a stationary sample handling assembly, elevating at least one sample container, reversibly securing the at least one sample container to a gripper assembly of the stationary sample handling assembly, and returning the at least one sample container to the ordered array after a weight measurement is taken, wherein the gripper assembly is connected to a balance, and is disengaged from other components of the sample handling assembly while the weight measurement is taken. 
     In yet another aspect, the invention relates to a weighing system for automated weighing of samples comprising a support frame; a balance secured to the support frame; a sample handling assembly operatively connected to the balance and secured to the balance; a moveable carrier for moving samples into position beneath the sample handling assembly; a lift assembly positioned beneath the moveable carrier and the sample handling assembly for lifting samples into position to be accessed by the sample handling assembly; and a data handling system for storing and processing of weight measurements of the samples. 
     The invention provides many of the benefits described herein by virtue of the close association of the sample handling assembly, including the gripper assembly, with the balance where the weight measurement is taken. The benefits provided by the invention are described in greater detail below. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a front perspective view of one embodiment of the apparatus of the invention. 
     FIG. 2 is a cut-away, top perspective view of the apparatus of the invention (balance and upper frame portion not shown). 
     FIG. 3 is a cut-away, top perspective view of the apparatus of the invention as in FIG. 2 (sample racks and carrier not shown). 
     FIG. 4 is a perspective view of the balance, sample handling, sample lift, and rack detection/identification components of the apparatus (viewed as from lower right to upper left of the view of FIG.  1  -sample racks, carrier, and frame not shown). 
     FIG. 5 is a top perspective view of the sample handling assembly. 
     FIG. 6 is a side elevational view of the sample handling assembly. 
     FIG. 7 is a perspective view of the sample lift assembly (viewed as from the upper right rear to the lower, left front of the view of FIG.  2 ). 
     FIG. 8 is an elevational view of the sample lift assembly (viewed as from the right of FIG.  2 ). 
     FIG. 9 is an elevational view of the sample lift assembly (viewed as from the right of FIG.  8 ). 
     FIG. 10 is a top elevational view of the sample lift assembly. 
     FIG. 11 is a top perspective view of the optional weighing isolation housing of the apparatus. 
     FIG. 12 is a side elevational view of the optional weighing isolation housing. 
     FIG. 13 is a front perspective view of one embodiment of the apparatus having the optional weighing isolation housing installed. 
     FIG. 14 is a block diagram of the control system, associated devices, and systems, according to one embodiment of the invention. 
     In the Figures, like reference characters indicate corresponding parts. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention provides solutions to many problems associated with automated weighing of multiple samples. In particular, the present invention allows large numbers of samples to be weighed rapidly. The invention also allows samples to be weighed with decreased opportunity for breakage and/or sample contamination. 
     Accordingly, in one aspect the invention relates to an automated weighing station comprising a support frame, a balance secured to the support frame, a sample handling assembly operably connected to the balance and secured to the balance, a moveable carrier for moving samples into position beneath the sample handling assembly, a lift assembly positioned beneath the moveable carrier and the sample handling assembly for lifting samples into position to be accessed by the sample handling assembly, and a control system for controlling the sample handling assembly, the lift assembly, and the moveable carrier in a coordinated manner, and for storing weight measurements of individual samples. The moveable carrier is coordinated with the operation of the lift assembly and the sample handling assembly via multiple positioning sensors which output to the control system, allowing rapid and safe handling of the samples, as well as providing data allowing each sample to be individually identified with its corresponding weight measurement when the data is stored or transferred in electronic form. 
     In a preferred embodiment, the sample handling assembly further comprises a gripper assembly comprising arms, one end of each arm being pivotably connected along a common pivot axis, and the opposite end of each arm comprising a gripper finger adapted to directly contact a sample container; a spring tensioner urging the arms toward one another; and a powered mechanical drive component in communication with the gripper assembly. More preferably, the mechanical drive component operates intermittently to spread the gripper arms against the force of the spring tensioner, thereby increasing the distance between the gripper fingers of the respective gripper arms such that a sample may be received therein, to be gripped by the fingers when the mechanical drive component releases the arms to return to a closed position as urged by the spring tensioner. The gripper assembly is designed to be small and light enough such that the net weight of individual samples is accurately weighed and recorded while the gripper assembly is operable connected to a component of the balance to actuate the weighing mechanism of the balance. When the actual weight measurement is accomplished, the mechanical drive component is dissociated from the gripper assembly, such that it does not interfere with an accurate measurement. 
     In another preferred embodiment, the moveable carrier comprises a sample rack carrier and a carrier support unit. More preferably, position sensors are provided which are adapted to communicate the position of the sample rack carrier in relation to the gripper assembly to the control system such that weight measurements of individual samples are stored electronically, and are associated with an individual sample by at least one identifying characteristic. Also more preferably, the sample racks are characterized by an asymmetric shape which requires that the sample racks be placed in the sample rack carrier in only one possible orientation relative to the moveable carrier. Also more preferably, a scanner is provided for determining the identity of sample racks within an array of racks held by the sample rack carrier. Also more preferably, the sample rack carrier comprises openings such that the scanner may determine the identity of sample racks disposed within the interior of the array of racks. More preferably, the sample racks are identified by the scanner utilizing a bar coding system. The sample rack carrier may be adapted to hold at least one rack which is adapted to hold a plurality of sample containers. More preferably, the sample rack carrier is adapted to allow access by the lift assemble to at least one sample container from beneath the sample rack carrier. This feature of the present invention provides significant benefits by allowing the overall movement of individual samples to be minimized, and controlled, because samples are moved in a short, substantially vertical path from the sample rack to the gripper assembly. 
     In a preferred embodiment, the carrier support unit further comprises at least one powered mechanical drive component adapted to provide controlled forward and rearward, left and right movement of the sample rack carrier. More preferably, the at least one powered mechanical drive component comprises a first electric motor controlling forward and rearward movement, and a second electric motor controlling left and right movement of the sample rack carrier. Additionally, position sensors outputting to the control system provide data allowing the individual identity of sample to be associated with their respective weight measurements as stored data. 
     In another preferred embodiment, the lift assembly comprises a housing; a powered mechanical drive component connected to the housing; and a lift shaft operably connected to the powered mechanical drive component, wherein the powered mechanical drive component provides controlled upward and downward movement of the lift shaft. More preferably, the lift shaft further comprises a tip which is adapted to receive the bottom portion of a sample container. More preferably, the tip is adapted to receive a bottom portion of a sample container, the shape of which is selected from the group consisting of rounded, conical, flat-ended cubical, and flat-ended circular. Most preferably, the powered mechanical drive component comprises an electric motor having a pulley engaged to a belt member, the distal portion of which engages a second pulley, and wherein the belt member is attached to a lift shaft mount to provide upward and downward motion of the lift shaft which is connected to the lift shaft mount. Position sensors allow coordination of the lift shaft movement with sample position relative to the moveable carrier and the sample handling assembly. These position sensors output to the control system to facilitate rapid but safe and efficient sample handling in conjunction with the operation of the sample handing assembly. 
     In another preferred embodiment, the automated weighing station further comprises a housing adapted to isolate a gripper assembly of the sample handling assembly. More preferably, the housing comprises a first sensor associated with an aperture for receiving a sample through a bottom plate of the housing, and a second sensor positioned adjacent to the gripper assembly, the first and second sensors allowing determination of a lowered position and a lifted position, respectively, of the sample. Most preferably, the housing further comprises at least one aperture for the introduction of gases for atmospheric control within the housing. The sensors output to the control system, allowing control of other moving components of the station, in conjunction with sample movement into, and out of, the housing. 
     In another aspect, the invention relates to a method of weighing multiple individual samples comprising moving an ordered array of sample containers beneath a stationary sample handling assembly, elevating at least one sample container, reversibly securing the at least one sample container to a gripper assembly of the stationary sample handling assembly, and returning the at least one sample container to the ordered array after a weight measurement is taken, wherein the gripper assembly is connected to a balance and is disengaged from other components of the sample handling assembly while the weight measurement is taken. 
     In a preferred embodiment, the weight of a sample within the individual sample container is between about 0.01 mg and about 500 g. More preferably, the weight of a sample within the individual sample container is between about 0.1 mg and about 50 g. Most preferably, the weight of a sample within the individual sample container is between about 1 mg and about 5 g. 
     In a preferred embodiment, the weight of a sample within the individual sample container is between about 1 mg and about 100 mg. More preferably, the weight of a sample within the individual sample container is between about 2 mg and about 50 mg. Most preferably, the weight of a sample within the individual sample container is between about 5 mg and about 25 mg. 
     The design of the gripper assembly and its operation by the mechanical drive component of the sample handling assembly allows accurate and precise measurements of net sample weight. 
     In yet another aspect, the invention relates to a weighing system for automated weighing of samples comprising a support frame; a balance secured to the support frame; a sample handling assembly operatively connected to the balance and secured to the balance; a moveable carrier for moving samples into position beneath the sample handling assembly; a lift assembly positioned beneath the moveable carrier and the sample handling assembly for lifting samples into position to be accessed by the sample handling assembly; and a data handling system for storing and processing of weight measurements of the samples. 
     In a preferred embodiment, the data handling system comprises a balance; computer software; and computer hardware; wherein the data handling system is adapted to communicate weight measurements to computer software and hardware. More preferably, the data handling system further comprises one or more data collectors positioned and adapted to transmit information to a computer control unit, thereby allowing coordinated movement of samples via the sample handing assembly, the moveable carrier, and the lift assembly, wherein the information is coordinated by the computer control unit with the storage of weight measurement transmitted by the balance for individual samples. Most preferably, the data handling system further comprises a scanner for detection of the position and identity of sample racks on the moveable carrier; at least one position sensor associated with the moveable carrier; and at least one sample position sensor associated with the sample handling assembly. 
     In another preferred embodiment, the computer hardware of the data handling system comprises one or more of the following: a display; data entry apparatus; a processor; an interface to the weighing apparatus; a printer or other output apparatus; electronic interfaces among the component parts; and memory. 
     In another preferred embodiment, the computer software of the data handling system comprises an operating system; a database program; a report generating program; a data-receiving program for receiving data from the weighing apparatus; and a control program for controlling the weighing apparatus. More preferably, the report generating program is adapted to provide data comprising individual sample identification related one or more of sample rack identity, sample position, tare weight of a sample container, gross weight of sample and sample container, and net weight of sample. More preferably, the data is originally stored in a format selected from the group consisting of ASCII text, binary, and ODBC (object database connectivity format). Most preferably, the data is originally stored in ASCII text format. Other formats may also be employed for data storage and transfer in particular situations. 
     Referring now to the Figures, it should be noted that like part numbers carry over from figure to figure, and describe the same part in all figures. Referring in particular to FIG. 1, a front perspective view of one embodiment of the automated weighing station  2  of the invention is shown. Enclosure and support frame  4  is shown supporting balance  6  and sample handling assembly  8 . Also shown is sample lift assembly  14 , sample rack carrier  10 , and carrier support unit  12 . 
     Frame  4  also provides support for materials which may be used in conjunction with frame  4  to enclose the automated weighing station  2 . Frame  4  may be constructed so as to allow access via a front, lift-type door in a conventional fashion, and/or via side access door openings, such that samples may be easily accessed before, during, or at the conclusion of an automated weighing run. 
     Sample lift assembly  14  functions to raise an individual sample to facilitate access to the sample by the sample handling assembly  8 . Accordingly, sample racks in sample rack carrier  10  have apertures beneath each individual sample compartment to allow access from below the sample. Carrier support unit  12  stably supports sample rack carrier  10 , and transports carrier  10  laterally to allow each individual sample to be brought into handling positions beneath sample handling assembly  8 . 
     FIG. 2 shows an embodiment of the apparatus of the invention, without showing frame  4  or balance  6  as shown in FIG.  1 . Motors  18  and  20  provide power for left-right, front-back movement of sample rack carrier  10  on carrier support unit  12 . Scanner  16  reads identifying information on the end of each sample rack, e.g. a bar code. In FIG. 2, scanner  16  is shown reading the front row of racks in carrier  10 . When the rear row of racks is being analyzed, scanner  16  reads the identifying information through apertures  17  in carrier  10 . Because of asymmetry in rack design, samples positioned within each rack are necessarily identified by rack identification. FIG. 3 is very similar to FIG. 2, except the sample racks and sample rack carrier  10  are not shown. Sample lift assembly  14  is shown mounted on carrier support unit  12 , and interacting with a sample container to facilitate reception of a sample by sample handling assembly  8 . 
     FIG. 4 shows the relative positioning and interaction between balance  6 , sample handling assembly  8 , and sample lift assembly  14 . Gripper assembly  24  is shown holding a sample for weighing in conjunction with sample lifting assembly  14 , powered by lifting motor  28 . Sample handling assembly  8  includes gripper spreader motor  22 . Although sample racks and sample rack carrier  10  are not shown in FIG. 4, scanner  16  is shown for the purpose of illustrating the relative positioning of components. 
     FIG. 5 is an enlarged depiction of sample handling assembly  8 . Gripper assembly  24  comprises gripper fingers  32  which directly contact sample container  30 . Gripper fingers  32  are connected to gripper arms  34  which are urged toward one another by spring  36 . Outer clevis  35  and inner clevis  37  connect the gripper arms  34  to mounting block  39  via shoulder screws  38 . Mounting block  39  is connected to balance shaft  40  via dowel pin  41  (as shown in FIG.  6 ). Balance shaft  40  is connected to balance  6  (see FIG. 4) via dowel pin  41  (see FIG.  6 ). 
     Gripper arms  34  of gripper assembly  24  are spread (against the tension provided by spring  36 ) by dowels  42  and  43 , which are connected to arm spreaders  44  and  46 , respectively. Arm spreader  44  is connected to and actuated by outer shaft  58 . Arm spreader  46  is connected to and actuated by inner shaft  57 . Outer shaft  58  and inner shaft  57  are supported by bearing  49  as they pass through front mount  50 . This connection is secured by snap rings  48 , which are disposed forward and rearward of front mount  50 . The rearward end of outer shaft  58  terminates prior to rear mount  54 , and is supported in relation to inner shaft  57  by bronze bushing  59 . Inner shaft  57  continues rearward through rear mount  54 , where it is supported by bearing  51 , and secured by snap rings  55 . 
     Outer arm rotator  56  and inner arm rotator  60  are connected to outer shaft  58  and inner arm shaft  57 , respectively. Arm rotators  56  and  60  are connected to rotator  64  via. dowels  62 . Rotator  64  is powered by stepper motor  22 , to actuated arm rotators  56  and  60 . The operation of rotator  64  is controlled by sensor  66  (e.g. an omron sensor), which operators via sensor flag  70 . Sensor bracket  68  provides the platform for mounting of sensor  66  and sensor flag  70 . The sensor assembly allows the coordination of the operation of sample handling assembly  8  with other components of the apparatus. In particular, operation of sample handling assembly  8  is coordinated with the operation of sample lift assembly  14 . 
     FIGS. 7-10 show various detailed views of sample lift assembly  14 . FIG. 7 is a front perspective view of the assembly; FIG. 8 is a front elevational view; FIG. 9 is a side elevational view (as from the right of FIG.  8 ); and FIG. 10 is a top elevational view of the assembly. 
     Lift motor  28 , mounted in bracket  88  on platform  90 , powers drive belt  78  via pulley  92 . At the upper end of sample lift assembly  14 , pulley  76  is mounted on an extension of rear mount  80  to carry drive belt  78 . Side mount  81  is connected along one edge to rear mount  80 , at its bottom to platform  90 , and on the lower portion of its front side to bracket  88 . On the side of drive belt  78  proximal to side mount  81 , bracket  82  is connected to lift shaft mount  74 . On the opposite side of lift shaft mount  74 , brackets  84  provide a mounting platform for sensor components and travel stops, which are coordinated with sensor components and travel stops  86  mounted on side mount  81  to control range of operation and range of travel of lift shaft mount  74  in conjunction with the operation of lift motor  28  and the drive assembly. Lift shaft  26  is mounted in lift shaft mount  74  and terminated at the upper end with tip  72 . Tip  72  may be configured variously, depending on the shape of the bottom of sample container  30 . In a preferred embodiment, tip  72  is cup shaped at the top to allow handling of containers with round bottoms. Conical or flat bottom containers may be handled by configuring tip  72  accordingly, as will be recognized by the skilled artisan. 
     The forward portion of sample handling assembly  8  may be isolated to facilitate certain weighing operations which require greater isolation of the sample or control of the atmospheric environment during the operation. Housing  92  may be optionally installed to provide this capacity (see FIG.  13 ). FIGS. 11 and 12 provide a top perspective and front elevational view, respectively, showing details of housing  92  (apparatus not shown). Top mounting plate  94  is provided with connection apertures  114  and bracket  112  for connecting housing  92  to the bottom of balance  6 . Aperture  116  allows passage of balance shaft  40  of the gripper assembly  24  to balance  6  when housing  92  is installed (gripper assembly  24  is contained within housing  92 ). 
     The lower compartment  96  of housing  92  is a substantially rectangular box having front and rear, left and right, and bottom plate  102  (see FIG.  12 ), with the top formed by attachment lower compartment  96  to top mounting plate  94 . Aperture  110 , in the rear side of lower compartment  96 , allows passage of outer and inner shafts  58  and  57 , such that gripper assembly  24  may be actuated within housing  92 . FIG. 12 shows lifted sample sensor  100 , secured by sensor bracket  98 . Seated sample sensor  106  is secured by sensor bracket  108 . Seated sample sensor  106  and bracket  108  are positioned adjacent to aperture  118 , which allows lifting of a sample container  30  (see FIGS. 5 and 6) through bottom plate  102  by lifting assembly  14 . Together this sensor arrangement allows precise coordination of the operation of lift assembly  14  and sample handling assembly  8 , when housing  96  is utilized. 
     FIG. 13 shows an embodiment of automated weighing station  2 , with housing  92  installed. 
     It will thus be seen that the objects set forth, among those made apparent from the preceding description, are efficiently obtained and, since certain changes may be made in carrying out the above embodiments and in the apparatus and method set forth, without departing from the spirit and scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense. 
     It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described and all statements of the scope of the invention which, as a matter of language, might be said to fall there between. 
     FIG. 14 is a block diagram of the control system, associated devices, and systems, according to one embodiment of the invention, wherein the blocks represent modules in the system and the arrows depict data flow to/from the modules.