Source: http://www.google.com/patents/US7722810?dq=7,403,220
Timestamp: 2014-08-01 23:12:39
Document Index: 768247065

Matched Legal Cases: ['Application No. 06076973', 'Application No. 08013740', 'Application No. 02773621', 'Application No. 02773621', 'Application No. 98951995', 'Application No. 2004', 'Application No. 2004']

Patent US7722810 - Apparatus and methods for automated handling and embedding of tissue samples - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign in<nobr>Advanced Patent Search</nobr>PatentsAn automated machine for handling and embedding tissue samples contained on microtome sectionable supports. The machine includes an input member configured to hold a plurality of the microtome sectionable supports prior to a tissue embedding operation. An output member is configured to hold a plurality...http://www.google.com/patents/US7722810?utm_source=gb-gplus-sharePatent US7722810 - Apparatus and methods for automated handling and embedding of tissue samplesAdvanced Patent SearchPublication numberUS7722810 B2Publication typeGrantApplication numberUS 11/010,773Publication dateMay 25, 2010Filing dateDec 13, 2004Priority dateSep 26, 2002Fee statusPaidAlso published asCA2491999A1, CA2491999C, CN1668908A, CN1684772A, CN100439894C, CN100518940C, CN101435753A, CN101435753B, EP1552266A1, EP1552266A4, EP2322938A1, EP2322938B1, US8034292, US8734735, US20050226770, US20100129859, US20110165615, US20110182783, WO2004029584A1Publication number010773, 11010773, US 7722810 B2, US 7722810B2, US-B2-7722810, US7722810 B2, US7722810B2InventorsDouglas P. Allen, Dominic P. DiNovo, Matthew J. Huddleston, Kenneth E. Hughes, George A. Keller, Keith A. Kuisick, Rebeccah P. Quam, Cecil R. Robinson, Jonathan E. Turner, Ernest D. VanHoose, Thomas J. Ward, Warren P. Williamson, IVOriginal AssigneeBiopath Automation, LlcExport CitationBiBTeX, EndNote, RefManPatent Citations (103), Non-Patent Citations (28), Referenced by (3), Classifications (15), Legal Events (3) External Links: USPTO, USPTO Assignment, EspacenetApparatus and methods for automated handling and embedding of tissue samplesUS 7722810 B2Abstract An automated machine for handling and embedding tissue samples contained on microtome sectionable supports. The machine includes an input member configured to hold a plurality of the microtome sectionable supports prior to a tissue embedding operation. An output member is configured to hold a plurality of the microtome sectionable supports after the tissue embedding operation. A cooling unit is configured to hold at least one of the microtome sectionable supports during the tissue embedding operation. A motorized carrier assembly is mounted for movement and configured to hold at least one of the microtome sectionable supports. The carrier assembly moves the support from the input member to the cooling unit and, finally, to the output member. A dispensing device dispenses an embedding material onto the microtome sectionable support and at least one tissue sample carried by the microtome sectionable support during the embedding operation.
1. An automated machine for embedding tissue samples on respective microtome sectionable supports, comprising:
at least one heater, said at least one heater coupled to at least one of said input member or the molds for heating the microtome sectionable supports.
2. The automated machine of claim 1, wherein each of said cooling units include at least one TEC.
3. The automated machine of claim 1, wherein the microtome sectionable support is received within a frame and is movable between a first position within the frame and a second position in which the embedded tissue sample is exposed for sectioning in a microtome, and the automated machine further comprises:
a staging device operative to move the support from the first position to the second position.
4. The automated machine of claim 3, further comprising a support assembly operatively coupled to a motor, the support assembly further coupled to said staging device and said dispenser, whereby the motor and support assembly are used to move said staging device and said dispenser together between the plurality of cooling units.
5. The automated machine of claim 1, further comprising:
a sensor operative to detect an amount of the embedding material dispensed onto the microtome sectionable support by said dispenser.
6. The automated machine of claim 1, wherein the input member comprises an elongate basket configured to hold and dispense a plurality of the microtome sectionable supports.
7. The automated machine of claim 6, wherein said elongate basket includes a dispensing opening and the machine further comprises:
8. The automated machine of claim 1, wherein the embedding material comprises paraffin, and the machine further comprises:
a reservoir coupled in fluid communication with said dispenser and configured to hold and heat the paraffin in a liquified form.
9. The automated machine of claim 1, wherein said carrier further comprises a pair of fingers configured to grip opposite sides of one of the microtome sectionable supports.
10. The automated machine of claim 1, further comprising:
a cabinet structure having an interior containing said cooling units, said motorized carrier assembly and said dispenser,
wherein said input member and said output member may be opened from outside said cabinet structure to allow the microtome sectionable supports to be loaded into the input member and, after embedding of the tissue samples, unloaded from the output member.
11. The automated machine of claim 10, wherein the input member comprises a hinged door.
12. The automated machine of claim 1, wherein said at least one heater further comprises:
respective heaters coupled to corresponding ones of said molds.
13. The automated machine of claim 12, wherein each one of the heaters is respectively incorporated into a corresponding one of said cooling units.
14. The automated machine of claim 1, wherein said at least one heater is coupled to said input member.
15. An automated machine for embedding tissue samples on respective microtome sectionable supports, comprising:
a dispenser operating to dispense an embedding material respectively onto the microtome sectionable supports and at least one tissue sample carried by each of the microtome sectionable supports during the embedding operation at least one heater, said at least one heater coupled to at least one of said input member or the molds for heating the microtome sectionable supports;
a first mold and a second mold thermally coupled with each cooling unit, said first mold being configured to receive a first microtome sectionable support and said second mold being configured to receive a second microtome sectionable support having a configuration different than the first microtome sectionable support; and
a sensor operative to detect the respective configurations of the first and second microtome sectionable support;
wherein said carrier assembly transports one of the microtome sectionable supports to either said first mold or said second mold depending on the configuration of the microtome sectionable support detected by said sensor.
16. An automated machine for embedding tissue samples on respective microtome sectionable supports, comprising:
a perforate input member configured to hold a plurality of the microtome sectionable supports prior to a tissue embedding operation, said perforate input member further constructed for receipt in a tissue processing machine and capable of resisting degradation from procedures used to fix and process the tissue in the tissue processing machine;
a cooling unit including a mold configured to hold at least one of the microtome sectionable supports during the tissue embedding operation;
a motorized carrier assembly mounted for movement and configured to hold at least one of the microtome sectionable supports and move the one support from said input member to said cooling unit to said output member;
a dispenser operating to dispense an embedding material respectively onto the microtome sectionable supports and at least one tissue sample carried by each of the microtome sectionable supports during the embedding operation; and
at least one heater, said at least one heater coupled to at least one of said input member or said mold for heating the microtome sectionable supports.
17. The automated machine of claim 16, wherein said cooling units include a TEC.
18. The automated machine of claim 16, wherein the microtome sectionable support is received within a frame and is movable between a first position within the frame and a second position in which the tissue sample is exposed for sectioning in a microtome, and the automated machine further comprises:
19. The automated machine of claim 18, wherein said staging device includes said dispenser.
20. The automated machine of claim 16, further comprising:
21. The automated machine of claim 16, wherein the input member comprises an elongate basket configured to hold and dispense the microtome sectionable supports.
22. The automated machine of claim 21, wherein said elongate basket includes a dispensing opening and the machine further comprises:
23. The automated machine of claim 16, wherein the embedding material comprises paraffin, and the machine further comprises:
24. The automated machine of claim 16, wherein said carrier further comprises a pair of fingers configured to grip opposite sides of one of the microtome sectionable supports.
25. The automated machine of claim 16, further comprising:
a cabinet structure having an interior containing said cooling unit, said motorized carrier assembly and said dispenser,
26. The automated machine of claim 25, wherein the input member comprises a hinged door.
27. The automated machine of claim 16, wherein said at least one heater is coupled to said mold.
28. The automated machine of claim 27, wherein said at least one heater is incorporated into said cooling unit.
29. The automated machine of claim 16, wherein said at least one heater is coupled to said perforated input member.
a first mold and a second mold thermally coupled with said cooling unit, said first mold being configured to receive a first microtome sectionable support and said second mold being configured to receive a second microtome sectionable support having a configuration different than the first microtome sectionable support; and
a sensor operative to detect the respective configurations of the first and second microtome sectionable supports;
31. An automated machine for embedding tissue samples on respective microtome sectionable supports, wherein each microtome sectionable support is received within a frame and is movable between a first position within the frame and a second position in which the tissue sample is exposed for sectioning in a microtome, the automated machine comprising:
a plurality of TEC units each including a mold configured to hold at least one of the microtome sectionable supports during the tissue embedding operation at least one heater, said at least one heater coupled to at least one of said input member or the molds for heating the microtome sectionable supports;
a motorized carrier assembly mounted for movement and configured to hold at least one of the microtome sectionable supports and move the one microtome sectionable support from said input member to one of said cooling units to said output member; and
a staging device mounted for movement between said cooling units and including a setting head operative to move the support from the first position to the second position and a dispenser operating to dispense an embedding material respectively onto the microtome sectionable supports and at least one tissue sample carried by each of the microtome sectionable supports during the embedding operation.
32. The automated machine of claim 31, further comprising:
a sensor operative to detect an amount of the embedding material dispensed onto the microtome sectionable support.
33. The automated machine of claim 31, wherein the TEC units each further comprise a support member with a cooling plate operated by a thermal electric control, and a mold coupled to said cooling plate, said mold configured to hold the microtome sectionable support and the embedding material dispensed by said dispenser.
34. The automated machine of claim 31, wherein the input member comprises an elongate basket configured to vertically hold and dispense a stack of the microtome sectionable supports.
35. The automated machine of claim 34, wherein said elongate basket includes a dispensing opening at a lower end thereof and further comprising:
a movable member configured to urge the microtome sectionable supports toward said lower end.
36. The automated machine of claim 31, further comprising a heater thermally coupled to said input member for heating the microtome sectionable supports.
37. The automated machine of claim 31, wherein at least two different sizes of microtome sectionable supports may be handled and embedded in the machine and the machine further comprises:
a first mold and a second mold thermally coupled with each TEC unit, said first mold configured to receive a microtome sectionable support of one configuration and said second mold configured to receive a microtome sectionable support of a different configuration; and
a sensor operative to detect the configuration of the microtome sectionable support, said carrier assembly responsive to the configuration detected by said sensor to transport one of the microtome sectionable supports to either said first mold or said second mold.
38. The automated machine of claim 31, wherein the embedding material comprises paraffin, and the machine further comprises:
39. The automated machine of claim 31, wherein said carrier further comprises a pair of fingers configured to grip opposite sides of one of the microtome sectionable supports.
40. The automated machine of claim 31, further comprising:
a cabinet structure having an interior containing said TEC units, said motorized carrier assembly and said dispenser,
wherein said input member and said output member may be opened from outside said cabinet structure to allow the microtome sectionable supports to be loaded into the input member and, after preparation of the tissue samples, unloaded from the output member.
41. The automated machine of claim 40, wherein the input and output members each comprise respective doors of the cabinet structure.
The present application is a continuation of PCT Serial No. PCT/US02/30779 filed on Sep. 26, 2002 (now pending), the disclosure of which is hereby fully incorporated by reference herein.
FIELD OF THE INVENTION The present invention generally relates to apparatus and methods for handling and embedding tissue samples for biopsy analysis and, more particularly, for handling and embedding such samples in an automated manner.
SUMMARY OF THE INVENTION The present invention generally relates to an automated machine for preparing tissue samples in respective microtome sectionable supports. The machine includes an input member configured to hold a plurality of the microtome sectionable supports prior to a tissue embedding operation. An output member is configured to hold a plurality of the microtome sectionable supports after the tissue embedding operation. A cooling unit is preferably configured to hold at least one of the microtome sectionable supports during the tissue embedding operation. More preferably, multiple thermal electric cooling (TEC) units are used for faster production, however, other cooling devices may be utilized without departing from the inventive principles. TECs are preferred because they can rapidly cycle between heating and cooling cycles. In accordance with the invention, initially cycling the TEC to heat the microtome sectionable support greatly assists with properly embedding the support. A motorized carrier assembly is mounted for movement and configured to hold at least one of the microtome sectionable supports. This carrier assembly moves the support from the input member to the cooling unit and, finally, to the output member. A dispensing device dispenses an embedding material onto the microtome sectionable support and at least one tissue sample carried by the microtome sectionable support during the embedding operation.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of an automated machine constructed in accordance with the preferred embodiment of this invention for handling and embedding tissue samples.
FIG. 27 is a flowchart illustrating a process executed by the control system of FIG. 17 to test a filled frame and cassette assembly, removed from a mold in the machine of FIG. 1.
DETAILED DESCRIPTION OF THE DRAWINGS Referring generally to FIGS. 1 and 2, an automated machine 10 constructed in accordance with the invention includes a housing 12 having a main door 14 on its front side. When open as shown in FIG. 1, main door 14 exposes an input door 16 and four separate output trays 18 a, 18 b, 18 c, 18 d which are removable for purposes to be described below. Tray 18 c is shown partially pivoted outwardly along its lower edge and ready to be lifted out of the machine 10. Doors 14 and 16 also pivot outwardly from their lower edges, however, doors 14 and 16 are attached to housing 12 by respective hinges 14 a, 16 a. The front side of housing 12 includes openings 20 which allow relatively cool room air to be drawn into thermal electric cooling devices as described below. Housing 12 includes a control panel 22 for operating the machine 10, a paraffin input opening 24 on its top side, and caster wheels 26 on its lower side. A lower inside portion 27 of housing 12 includes the various control components necessary to operate machine 10 as will be described below. As further shown in FIG. 2, paraffin input 24 leads to a container 28 for holding the liquid paraffin. Container 28 is heated to maintain the liquid paraffin at the proper temperature of about 60� C. As generally shown in FIG. 2, input door 16 leads to a cassette and frame assembly dispenser 30 while output trays 18 a, 18 b, 18 c, 18 d (FIG. 1) include individual cassette and frame assembly receivers 32 a, 32 b, 32 c, 32 d inside housing 12. Each receiver 32 a-d has two vertical rows of spring-biased slots, each slot retaining a single cassette and frame assembly after the embedding operation is complete The machine 10 is loaded with cassette and frame assemblies each containing one or more tissue samples, in cassette and frame assembly dispenser 30. The cassette and frame assemblies or, more broadly speaking, the microtome sectionable supports, may take any suitable form. Preferably, these supports are generally of a form as described in U.S. Pat. No. 5,817,032, and further described below. The tissue samples are embedded in paraffin using the components and methods to be described below before being individually placed within the respective cassette and frame assembly receivers 32 a, 32 b, 32 c, 32 d. Referring now to FIG. 3, a pick and place robot 40 includes a pick and place head 42 which is movable along three axes. Specifically, a base 44 rides left and right on rails 46, 48 along a horizontal x-axis as viewed from the front of machine 10. Pick and place head 42 further rides on rails 56, 58 along a horizontal y-axis, that is, toward and away from the front of machine 10. A vertical support 50 carries pick and place head 42 and rides up and down on rails 52, 54 along a vertical z-axis. To achieve these respective movements, three separate motor and drive screw assemblies 60, 62 and 64 are provided. Motor 60 a and drive screw 60 b move base 44 along rails 46, 48. Motor 62 a and drive screw 62 b move pick and place head 42 vertically along rails 52, 54. Motor 64 a and drive screw 64 b move pick and place head 42 in opposite directions along rails 56, 58. Although belt driven screws are shown, it will be appreciated that direct drives or any other types of motive devices may be used instead. For all of the various electrical wiring that is necessary for the motors and control components, flexible conduits 66, 68, 70 are provided to facilitate the various movements of the pick and place robot 40.
Turning to FIGS. 4, 4A and 4B, a plurality of, for example, four input baskets 100 are provided to hold the cassette and frame assemblies and their respective tissue samples for dispensing purposes. Access by pick and place head 42 is provided by an opening 101 a in an interior cover 101. Each basket 100 is retained in a heated receptacle 102 on the inside surface of door 16. Preferably, receptacles 102 each include one or more cartridge style heaters 103 which maintain baskets 100 and the cassette and frame assemblies therein at an elevated temperature designed to keep any remnant paraffin remaining from the previous tissue processing procedure in a liquified state until the start of the cooling process. That is, solidification of the paraffin is prevented so that the various components which need to move are able to without jamming. Suitable thermal insulation 105 may be provided between receptacles 102. Solidified or partially solidified paraffin on the baskets 100 and/or the cassette and frame assemblies therein may also tend to cause jamming of baskets 100 in receptacles 102 or jamming of the cassette and frame assemblies in baskets 100. Baskets 100 are preferably transferred by the operator, such as a histotechnician, directly into receptacles 102 from a tissue processing machine, however, this may instead be an automated transferring operation. Baskets 100 are perforated and constructed of a material suitably resistant to heat, chemicals, microwaves, or other environmental conditions present during tissue processing. A suitable material is Ultem�, available from General Electric Co. Baskets 100 may be accessed by opening door 16 via hinge mechanisms 16 a, 104 (FIG. 4) and then opening a spring-loaded hinged closure 106 at the top of a basket receptacle 102. Each basket receptacle 102 further includes a lower, spring-loaded retaining member 110 which flips outwardly as a cassette and frame assembly is withdrawn from basket 100 and is then biased to the vertical position shown to retain the next successive cassette and frame assembly in position to be grasped by the pick and place head 42. A basket presence sensing assembly 112 is mounted to the inside surface of door 16 and is actuated when a basket 100 is fully inserted downwardly into receptacle 102 to thereby indicate to the control system that a basket 100 is present. Although such sensors may take many forms, in this case an actuation member 114 (FIG. 4A) is received in a slot 116 of basket 100 and is thereby moved downwardly such that an attached element 118 moves vertically into and is sensed by a presence sensor 119.
Referring to FIGS. 7-10A and 10B, stager/filler 172 more specifically includes a support assembly 195 which is rigidly fastened to four linear bushings or bearing blocks 188 a, 190 a riding along rails 188, 190. Support assembly 195 is also rigidly fastened to a mounting member 196 which rides along screw 194 via a nut 197. Thus, motor 192 turns screw 194 through nut 197 and thereby moves support assembly 195 along rails 188, 190. A generally U-shaped support member 198 is a rigid part of assembly 195. As previously discussed, another motor 184 provides the motive force for vertical movement of stager/filler 172. Motor 184 includes a mounting portion 184 a rigidly coupled to a mounting portion 195 a of support assembly 195 and a rotatable portion 184 b. A bearing 199 is held within a mounting hole 198 b and supports screw 186 during rotation. Rotatable portion 184 b of motor 184 is rigidly coupled to screw 186 such that screw 186 may be rotated within U-shaped support member 198. Stager/filler 172 further includes a vertical support member 202 carrying a nut 204 which engages screw 186. Vertical support member 202 is thereby moved along rail 182 via linear bushings 182 a which are rigidly fastened to vertical support member 202. Rail 182 is rigidly fastened to a portion 195 b of support assembly 195. Vertical support member 202 carries four fingers or pushers 203 which push cassette 150 a through frame 150 b and within base mold 82 to the position shown in FIGS. 9 and 10. Heaters 205 are also coupled to pushers 203 to maintain them at an elevated temperature (e.g., 60�-65� C.). Vertical movement of pushers 203 is accomplished by activating motor 184 and screw 186 such that vertical support member 202 carried by nut 204 moves downwardly along rail 182 and, as a result, moves pushers 203 downwardly against the top corner portions of cassette 150 a. Simultaneously, vertical support member 202 moves four spring-loaded holding members 206 (only two shown) downwardly against the top corner portions of frame 150 b to immobilize the frame 150 b during the staging and paraffin filling process (FIG. 10A). After the staging process is complete, the bottom of the cassette 150 a is exposed outwardly of the frame 150 b and within the interior of the base mold 84.
At this point, as shown in FIG. 10B, the fingers or pushers 203 are withdrawn upwardly by motor 184 to a position at which they will not contact any paraffin 205 while the spring-loaded holding members 206 still retain frame 150 b against base mold 84 with some spring pressure. Liquid paraffin 205 is then dispensed into base mold 84 and throughout the cassette 150 a to thereby embed the tissue sample 210. To this end, a dispensing tube 212 receives the paraffin from a suitable valve 214 and tubing 216 (FIG. 9) which is coupled to container 28 (FIGS. 2 and 3). As with all components which will be in close thermal contact with the paraffin, these components are preferably maintained at an elevated temperature of about 60�-65� C. Dispensing tube 212 is preferably heated by a cartridge heater 220 controlled by an RTD and thermal fuse assembly 224. Tubing 216 may be similarly heated, if necessary. The paraffin is preferably dispensed by gravity, although a pump may be used if necessary. Limit switches 230, 232 (FIG. 9) monitor the position of the vertical support member 202 at upper and lower limits. The intermediate position used during the filling procedure to raise pushers 203 above the paraffin level may be controlled by simply rotating the screw 186 a predetermined amount. An ultrasonic level sensor 234 (Model No. ML102 obtained from Cosense, Inc. of Hauppauge, Long Island, N.Y.) is mounted to the stager/filler 172 to sense when the level of liquid paraffin is correct, that is, preferably near the top of frame member 150 b. At this point, the valve 214 is closed to stop dispensing paraffin from the dispensing tube 212. Level sensing is preferred because various amounts of paraffin will need to be added to each base mold depending on the amount of tissue in each cassette 150 a. Thus, level sensing assures that there is no overflow or underfill of paraffin in the base mold 82 or 84.
The control 352 is further connected to a thermal electric 3-state controller 366 that controls the operation of each of the 16 TEC plates 236 associated with each of the 8 pairs of base molds 82, 84. Each TEC plate 236 has a corresponding RTD 368 that provides a temperature feedback signal to the controller 366 representing the temperature of its respective TEC plate 236. Referring to FIG. 18, the thermal electric 3-state controller 366 has a microcontroller 370 driven by a clock 372. It should be noted that although the machine has only 16 TEC plates 236, the controller 366 is built to accommodate 24 TEC plates 236. The microcontroller 370 includes software modules providing a system interface 374, a TEC loop state machine 376, a calibration algorithm 378 and an A/D converter and signal processor 380. The controller 370 controls all 16 TEC plates 236 and can be configured to control fewer or more TEC plates 236. In order to accommodate such a large number of devices, that is, 24 TEC plates 236 and 24 RTDs 368, a complex programmable logic device (�CPLD�) 388 is used as an interface device between the microcontroller 370 and the TEC plates 236 and RTDs 368. A loop clock 382 provides successive time windows that are adjustable by the loop clock state machine 393 of the CPLD 388. During each time window, in response to a command from the microcontroller 370, the A/D converter state machine 389 within the CPLD 388 causes outputs from all of the RTDs to be multiplexed into the A/D converter 384. During each time window, RTD outputs are read by the microcontroller 370 as part of the microcontroller 370 regulating the operation of each of the TEC plates 236 in response to commands from the control 352 (FIG. 17). If the operating state of any of the TEC plates 236 is to be changed, a state of a MOSFET current switch 395 within the TEC interface 392 must be changed; and that new state is transferred to the MOSFET control state machine 391 of the CPLD 388. That new state is then supplied via a respective driver 390 to a respective current switch 395. Thus, the measured temperatures provided by respective RTDs 368 are maintained in close correspondence to the temperatures commanded by the control 352 (FIG. 17).
A signal requesting one of the four tray latches be opened can be provided by input devices 417, for example, a push button on the machine or a button on the touchscreen of the user I/O 354 (FIG. 17). In response to that request, microcontroller 398 operates the pulse width modulator (�PWM�) 404 to provide output signals to a PWM selection switch 418 that, in turn, provides actuation and hold currents via an amplifier 422 to an appropriate one of the MOSFET current switches 423. That MOSFET current switch 423 operates a respective one of the four tray latch solenoids 97, thereby releasing a latch or interlock so that a tray can be pivoted outward and removed. Similarly, in response to a command from the control 352, the microcontroller 398 operates the PWM 406 to provide actuation and hold currents signals to a valve solenoid 215 via two-way PWM switch selection 420, amplifier 424 and MOSFET current switches 425.
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