US20180156698A1 - Pathologic staging compression apparatus and methods - Google Patents
Pathologic staging compression apparatus and methods Download PDFInfo
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- US20180156698A1 US20180156698A1 US15/572,564 US201615572564A US2018156698A1 US 20180156698 A1 US20180156698 A1 US 20180156698A1 US 201615572564 A US201615572564 A US 201615572564A US 2018156698 A1 US2018156698 A1 US 2018156698A1
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- compression
- tube
- compression device
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- A—HUMAN NECESSITIES
- A47—FURNITURE; DOMESTIC ARTICLES OR APPLIANCES; COFFEE MILLS; SPICE MILLS; SUCTION CLEANERS IN GENERAL
- A47J—KITCHEN EQUIPMENT; COFFEE MILLS; SPICE MILLS; APPARATUS FOR MAKING BEVERAGES
- A47J19/00—Household machines for straining foodstuffs; Household implements for mashing or straining foodstuffs
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B30—PRESSES
- B30B—PRESSES IN GENERAL
- B30B9/00—Presses specially adapted for particular purposes
- B30B9/02—Presses specially adapted for particular purposes for squeezing-out liquid from liquid-containing material, e.g. juice from fruits, oil from oil-containing material
- B30B9/04—Presses specially adapted for particular purposes for squeezing-out liquid from liquid-containing material, e.g. juice from fruits, oil from oil-containing material using press rams
- B30B9/047—Control arrangements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B30—PRESSES
- B30B—PRESSES IN GENERAL
- B30B9/00—Presses specially adapted for particular purposes
- B30B9/02—Presses specially adapted for particular purposes for squeezing-out liquid from liquid-containing material, e.g. juice from fruits, oil from oil-containing material
- B30B9/04—Presses specially adapted for particular purposes for squeezing-out liquid from liquid-containing material, e.g. juice from fruits, oil from oil-containing material using press rams
- B30B9/06—Presses specially adapted for particular purposes for squeezing-out liquid from liquid-containing material, e.g. juice from fruits, oil from oil-containing material using press rams co-operating with permeable casings or strainers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B30—PRESSES
- B30B—PRESSES IN GENERAL
- B30B9/00—Presses specially adapted for particular purposes
- B30B9/02—Presses specially adapted for particular purposes for squeezing-out liquid from liquid-containing material, e.g. juice from fruits, oil from oil-containing material
- B30B9/26—Permeable casings or strainers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
- G01N1/06—Devices for withdrawing samples in the solid state, e.g. by cutting providing a thin slice, e.g. microtome
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
- G01N2001/1006—Dispersed solids
- G01N2001/1012—Suspensions
- G01N2001/1025—Liquid suspensions; Slurries; Mud; Sludge
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/10—Devices for withdrawing samples in the liquid or fluent state
- G01N2001/1062—Sampling under constant temperature, pressure, or the like
Definitions
- the invention pertains to the field of pathologic staging. More particularly, the invention pertains to apparatus and methods for preparing a biological sample for pathologic staging.
- the pathologic stage is an essential piece of diagnostic information which is used to determine a cancer patient's prognosis and treatment, including whether or not the patient will receive chemotherapy.
- the surgeon To determine the pathologic stage of colorectal cancer, the surgeon first resects a section of fatty tissue from the patient's abdomen. This fatty tissue is then sent to the surgical pathologist, whose responsibility is to determine the stage of the illness based on the extent of cancer observed within this tissue. Importantly, the pathologist is not interested in the fat itself, but rather in the fibrous tissue and lymph nodes that are contained within the fatty tissue.
- the pathologist meticulously dissects the fatty tissue with a scalpel in search of fibrous material and lymph nodes.
- the pathologist removes any clearly visible nodes or other relevant fibrous tissue for examination under the microscope.
- some very small or microscopic pieces of tissue are left behind, but the presence or absence of any diagnostically relevant information (which may be microscopic) within the resected tissue may change the patient's prognosis and treatment.
- the pathologist conventionally selects five to ten random samples from the tissue for microscopic study.
- tissue is removed from the acetone bath and loaded into a specialized tube that is perforated with small (1 to 2 mm diameter) holes.
- An arbor press which is a mechanical device using a rack and pinion gear to exert a linear force, is then used to compress the sample in the tube. Compressing the sample forces the fatty components to be extruded out of the small holes in the tube.
- ACM represents a more time-efficient approach for processing the tissue than conventional hand dissection.
- ACM eliminates the risk that the pathologist may overlook diagnostically relevant information, therefore increasing the accuracy of the pathologic staging process for cancers of this type.
- Lymph nodes are usually the first organs invaded by malignant cells when they metastasize from the primary tumor site.
- the determination of the presence or absence of metastases in local lymph nodes is critical in determining the prognosis and treatment of the patient.
- ACM is capable of providing double or even quadruple the number of lymph nodes, compared to the conventional technique of tedious dissection. Not only does ACM relieve the pathologist of most of this dissection, it does a better job by allowing the fat to be processed in an economical and practical manner.
- a pathologic staging compression device prepares a biological sample for pathologic staging by compressing the sample to remove liquid fat from the sample.
- the apparatus preferably includes a compression tube with flange and a clamping plate to stabilize and align the compression tube, a fat containment and drainage system, a gauge to monitor the extrusion force, use of hydraulic pressure to generate the extrusion force for sample compression, and integrated ejection of the compressed sample and plunger.
- the apparatus preferably includes a compression tube, a drainage planum to hold and align the compression tube, a fat containment and drainage system, a gauge to monitor the extrusion force, use of hydraulic pressure to generate the extrusion force for sample compression, and ejection of the compressed sample after the compression tube has been removed from the drainage planum.
- FIG. 1 shows an isometric view of a pathologic staging compression apparatus in an embodiment of the present invention.
- FIG. 2 shows a front view of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 3 shows a side view of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 4 shows an isometric view of the compression assembly of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 5 shows a front view of the compression assembly of FIG. 4 .
- FIG. 6 shows a side view of the compression assembly of FIG. 4 .
- FIG. 7 shows an exploded view of the compression assembly of FIG. 4 .
- FIG. 8 shows an exploded view of the fat containment and drainage sub-assembly of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 9 shows an exploded view of the compression tube sub-assembly of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 10 shows an exploded view of the riser plate sub-assembly of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 11 shows an isometric view of the compression tube of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 12 shows a side view of the compression tube of FIG. 11 .
- FIG. 13 shows a cross sectional view of the fat containment and drainage system of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 14 shows a partial cross sectional view of the compression system of the pathologic staging compression apparatus of FIG. 1 .
- FIG. 15 shows another embodiment of a pathologic staging compression apparatus.
- FIG. 16 shows a front view of the pathologic staging compression apparatus of FIG. 15 .
- FIG. 17 shows a side view of the pathologic staging compression apparatus of FIG. 15 .
- FIG. 18A shows a view of the removable drainage planum in the compression assembly.
- FIG. 18B shows a top view of the removable drainage planum in the compression assembly.
- FIG. 18C shows a drainage plug that may be used in combination with the drainage planum of FIGS. 18A and 18B .
- FIG. 19 shows the compression tube and the removable drainage planum.
- FIG. 20 shows a hand plunger to be used with the apparatus.
- FIG. 21 shows an assembly of the hand plunger and compression tube on the bottom plug.
- FIG. 22 shows the pathologic staging compression apparatus with the drainage planum in an embodiment of the invention.
- FIG. 23A shows detail of the magnet and pins from circle 23 of FIG. 22 .
- FIG. 23B shows detail of the magnet and pins from circle 23 of FIG. 22 .
- FIG. 24A shows an embodiment with a mesh filter/disk and a compression tube.
- FIG. 24B shows a top view of the embodiment of FIG. 24A .
- FIG. 24C shows another view of the embodiment of FIG. 24A .
- FIG. 25 shows a mesh/disk filter. Perforation size of the mesh disk may vary.
- FIG. 26 shows an embodiment with a mesh sleeve or bag and a compression tube. Perforation size of the mesh sleeve or bag may vary.
- FIG. 27A shows a view of the mesh sleeve or bag of FIG. 26 , which may include a mesh base.
- FIG. 27B shows another view of the mesh sleeve or bag of FIG. 26 .
- FIG. 28A shows a compression tube with a 8 ⁇ 20 hole pattern.
- FIG. 28B shows a compression tube with a 1 ⁇ 20 slot pattern.
- FIG. 28C shows a compression tube with a 1 ⁇ 14 spiral pattern.
- FIG. 28D shows a compression tube with no perforations.
- FIG. 29 shows a block diagram of an example of an automated control system for the compression device.
- FIG. 30 shows a flow diagram of a use cycle of an automated control system for the compression device.
- ACM acetone compression method
- a pathologic staging compression apparatus preferably allows surgical pathologists to determine the pathologic stage of certain cancers, including, but not limited to, colorectal, breast, sarcoma, soft tissue and ovarian cancers, with greater accuracy and efficiency than is possible with conventional methods and apparatus.
- the compression apparatus may be used to pathologically stage any cancer where fatty tissue is present.
- Use of this apparatus as part of ACM preferably provides higher quality samples for pathologic staging. Any resected fatty tissue mass, human or animal, which is sent to a pathologist may utilize acetone treatment and the compression apparatuses described herein.
- the pathologic stage an essential piece of diagnostic information, is used to determine a cancer patient's prognosis and treatment, including whether or not the patient will receive chemotherapy.
- Better pathologic staging can help a clinician determine the best chemotherapy dosage for each individual patient.
- a directed, specific and measured dose of chemotherapy can be individually tailored to the patient based on the diagnostic result indicated in pathologic staging.
- a pathologic staging compression apparatus preferably includes a tube flange and a clamping plate for stabilization and alignment of the compression tube, a fat containment and drainage system, monitoring of the extrusion force being applied, use of hydraulic force for generation of the extrusion force for sample compression, and integrated ejection of the sample and plunger as improvements to the prior art apparatus. Being able to measure and monitor the extrusion pressure or extrusion force is essential to standardizing sample processing.
- a pathologic staging compression apparatus preferably allows surgical pathologists to perform ACM with greater ease, safety, accuracy, reliability, and replicability than the prior art device described in the academic literature.
- a frame of the pathologic staging compression apparatus supports a hydraulic ram held in alignment with the compression tube of a compression assembly on the frame.
- a pressure gauge/sensor measures the pressure of the hydraulic fluid being used to actuate the hydraulic ram. A measurement of the force exerted onto the tissue sample can be extrapolated from this value.
- the compression tube is mounted on a clamping plate between two flanges on the compression tube.
- the compression tube includes an array of small through-holes through the cylindrical wall of the compression tube.
- the clamping plate aligns the compression tube with the hydraulic ram and prevents movement of the compression tube during a compression cycle.
- the clamping plate is mounted onto a riser plate by way of a pair of thumb nuts. The riser plate is mounted to the frame.
- the tissue sample presoaked in acetone is placed in the compression tube with the bottom plug press-fit into the bottom of the compression tube.
- a shield is mounted around the compression tube as part of a liquid fat containment system.
- the compression tube is mounted onto the clamping plates and the plunger is placed on top of the compression tube. Slots in the clamping plates allow the clamping plates to slide between an engaged position and a retracted position. In the engaged position, the clamping plates are slid firmly against the exterior diameter of the compression tube and the thumb nuts are tightened. In the retracted position, the compression plates, slidable when the thumb nuts are loosened, are slid laterally away from the compression tube.
- the operator places the compression tube on top of the riser plate with the clamping plates in the retracted position.
- the operator slides the clamping plates towards the compression tube until they are firmly pressed against the exterior diameter of the compression tube before locking the thumb nuts.
- This action preferably automatically locates the compression tube on-center in relation to the hydraulic ram; no further adjustment beyond sliding the clamping plates inward and tightening the thumb nuts is necessary.
- a jack is actuated to raise the compression sub-assembly in the frame until the plunger contacts the hydraulic ram.
- the hydraulic pump is then actuated to drive the hydraulic ram to compress the tissue sample.
- a stop block below the compression tube is removed and the hydraulic ram is further driven to push the bottom plug out the bottom of the compression tube.
- the bottom plug is then removed and the hydraulic ram is further driven to eject the compressed sample from the bottom of the compression tube.
- the thumb nuts are loosened and the clamping plates are slid into the retracted position, after which the tube can be lifted off the riser plate.
- the riser plate sub assembly of the frame of the pathologic staging compression apparatus is replaced by a drainage planum or platform.
- the bottom plug is permanently fixed onto the drainage planum in this embodiment.
- the drainage planum is preferably removed from the frame of the device during each use cycle.
- the user first removes the drainage planum from the frame of the device.
- the user places the compression tube onto the drainage planum using the bottom plug affixed to the drainage planum.
- the tissue sample presoaked in acetone is then placed in the compression tube and preferably subject to an initial hand compression using a hand plunger.
- a shield is placed around the compression tube, its base resting on the surface of the drainage planum as part of a liquid fat containment system. Any fat extruded during the initial hand compression is drawn out of the drainage planum via an integrated drainage hole.
- the drainage planum is then mounted onto the frame of the device.
- the drainage planum is preferably located on the frame using locating pins and held in place by fasteners, such as magnets (for example neodymium magnets). Removal of the sample from the device occurs by first removing the compression tube from the drainage planum. The sample is then ejected from the compression tube using a hand plunger.
- fasteners such as magnets (for example neodymium magnets).
- tissue samples instead of tissue samples being placed directly into the compression tube, the tissue samples are placed in a disposable medical grade mesh bag/sleeve. The sleeve is then placed into the compression tube for processing.
- the use of mesh sleeves simplify cleaning of the compression tube.
- a mesh disk/filter acts as the bottom of the compression tube.
- the shape and size of the perforations in the compression tube may vary.
- the perforations may be designed to work in conjunction with these mesh devices.
- the width/diameter of the perforations may increase and the shape may change from circular perforations to slit-shaped perforations.
- These slit-shaped perforations may be arranged vertically along the circumference of the compression tube or arranged in some other manner, such as an involute spiral pattern.
- the compression tube may lack perforations entirely.
- the hydraulic pump of the compression staging apparatus may be mounted directly onto the frame of the device or not mounted directly onto the frame of the device.
- the pathologic staging compression apparatus 10 includes a frame 6 , a hydraulic ram 4 , a hydraulic hose 12 , a hydraulic pump 14 , a pressure gauge 2 , and a compression assembly 8 .
- the frame 6 supports and positions the hydraulic cylinder 4 and the compression tube 46 .
- the hydraulic ram 4 provides a compression force to compress a sample 9 in the compression assembly 8 .
- the hydraulic hose 12 delivers hydraulic oil from the hydraulic pump 14 to the hydraulic ram 4 .
- the hydraulic pump 14 actuates the hydraulic ram 4 .
- the pressure gauge 2 registers and displays the hydraulic pressure.
- the compression assembly 8 includes a perforated compression tube 46 , a fat containment tube or shield 16 , a clamping plate 22 , a riser plate 24 , fasteners 28 (for example, thumb nuts), a stop block 26 , and a drainage tube 20 .
- the shield 16 is preferably made of a clear plastic material. In one preferred embodiment, the shield 16 is made of polycarbonate.
- the compression assembly 8 includes a fat containment and drainage sub-assembly 30 , a compression tube sub-assembly 40 , and a riser plate sub-assembly 60 .
- the fat containment and drainage sub-assembly 30 includes the clear plastic shield 16 to contain the extruded liquid fat from the sample 9 , a mounting plate 34 to support the clear plastic shield 16 and provide a drainage hole 36 (see FIG. 13 ) for drainage of the fat, an o-ring 32 to provide a liquid tight seal between the clear plastic shield 16 and the mounting plate 34 , and the drainage tube 20 receiving the drained liquid fat from the drainage hole 36 in the mounting plate 34 and directing the drained liquid fat.
- the compression tube sub-assembly 40 includes a plunger 42 to compress the sample in the compression tube 46 , an o-ring 44 to provide a liquid tight seal between the compression tube 46 and the mounting plate 34 for the clear plastic shield 16 , the compression tube 46 in the form of a perforated 47 compression vessel 46 that contains the sample 9 and allows for extrusion of liquid fat through the perforations 47 , and a bottom plug 48 to seal the opening at the bottom of the compression tube 46 during compression.
- the riser plate sub-assembly 60 includes a riser plate 24 to provide a platform for the compression tube 46 , a stop block 26 to hold the bottom plug 48 in position during compression, clamping plates 22 to stabilize and secure the compression tube 46 , and a pair of fasteners 28 (for example, thumb nuts) to lock the clamping plates 22 and thereby secure the compression tube 46 .
- liquid fat is extruded out small perforations 47 in the compression tube 46 .
- the compression tube 46 has an interior space in the range of 1.2 to 12 cubic inches (20 to 200 cubic centimeters) in volume to receive a sample.
- the volume of the compression tube 46 varies depending on the size of the sample being treated.
- the size and number of perforations are selected to be large enough for liquid fat to pass through them, but small enough that fibrous tissue cannot.
- the perforations are about 3/64′′ (1.2 mm) in diameter.
- An o-ring seating groove 52 provides a seat for the o-ring 44 forming a seal between the compression tube 46 and the clear plastic shield 16 .
- a flange 54 along the lower edge of the tube 46 allows for stabilization and alignment of the compression tube 46 when used in conjunction with the clamping plates 22 .
- a secondary flange 56 allows for the mounting of the fat containment and drainage sub-assembly 30 onto the compression tube 46 .
- the plunger 42 and the bottom plug 48 seal the top and bottom of the compression tube 46 , respectively, to maintain the sample within the compression tube 46 during compression.
- the o-rings 44 seal the mounting plate 34 with respect to the clear plastic shield 16 and the compression tube 46 such that the liquid fat extruded from the compression tube 46 drains out the drainage hole 36 .
- the drainage tube 20 mounts on a tubing barb 38 extending from the bottom of the mounting plate 34 .
- the hydraulic ram 4 aligns with the opening in the top of the compression tube 46 and contacts and drives the plunger 42 downward to compress the sample 9 in the compression tube 46 using the hydraulic force generated by the hydraulic pump 14 .
- the sample 9 is preferably ejected by removing the stop block 26 from below the bottom plug 48 and then actuating the hydraulic ram 4 farther in the direction of actuation 70 until the bottom plug 48 is driven out the bottom of the compression tube 46 and into the space previously occupied by the stop block 26 , where it may be easily removed from the apparatus by the user.
- the compressed sample 9 is then driven out the bottom of the compression tube 46 and into the space previously occupied by the stop block 26 , where it may be removed by hand either before or after sliding the clamping plates 22 to the retracted position and lifting the compression tube sub-assembly 40 off the riser plate 24 .
- the riser plate subassembly 60 shown in the embodiment of FIGS. 1-14 is replaced by a removable drainage planum 81 .
- the bottom plug 82 (see FIG. 19 ) is permanently fixed onto the drainage planum 81 .
- the drainage planum 81 is preferably designed to be removed from the frame 6 of the compression staging apparatus 80 during each use cycle.
- FIGS. 18-21 Details of the bottom plug 82 , drainage planum 81 and compression tube 46 of the compression assembly 85 are shown in FIGS. 18-21 .
- the user first removes the drainage planum 81 and the bottom plug 82 from the frame 6 of the compression staging apparatus 80 .
- the compression tube 46 is then placed onto the drainage planum 81 using the bottom plug 82 affixed to the drainage planum 81 .
- the tissue sample 9 is then loaded into the compression tube 46 and preferably given an initial hand compression in the direction of the arrow 92 in FIG. 21 using a hand plunger 90 .
- the hand plunger is made of an acetal resin.
- Any fat extruded during an initial hand compression drains out of the drainage planum 81 via an integrated drainage hole 83 , shown in FIG. 18B .
- a drainage plug 93 which is shaped to fit into and plug the drainage hole 83 when inserted into the drainage hole 83 , is shown in FIG. 18C .
- the drainage planum 81 is then mounted onto the frame 6 of the compression staging apparatus 80 .
- the drainage planum 81 is reversibly affixed to the frame 6 using locating pins 84 and locating pin holes 89 and held in place by magnets 86 and 87 , for example neodymium magnets, as shown in FIGS. 22, 23A and 23B .
- a planum alignment plate 91 aids in affixing the frame 6 to the drainage planum 81 .
- ejection of the sample occurs by first removing the compression tube 46 from the drainage planum 81 .
- the sample 9 is then preferably ejected from the compression tube 46 using a hand plunger 90 .
- the sample 9 is preferably ejected from the compression tube 46 using the stop block 26 .
- the shield 16 is preferably placed around the compression tube 46 , with the base of the shield 16 resting on a surface of the drainage planum 81 .
- the shield 16 that contains the spray from the extrusion of liquefied fat is preferably mounted directly onto the compression tube 46 using the mounting plate 34 , as shown in FIG. 8 .
- the hydraulic pump is not mounted directly on the device (for example in the apparatus 10 shown in FIGS. 1-14 ). In alternative embodiments, the hydraulic pump 88 is mounted directly onto the frame 6 of the apparatus 80 , as shown in FIG. 15 .
- the bottom plug 48 , 82 is a mesh disk filter 97 , as shown in FIGS. 24 and 25 .
- a mesh disk filter 97 for the bottom plug 48 , 82 permits the fat to be released from the device through the bottom of the compression tube 46 , in addition to or instead of through the perforations 47 in the compression tube 46 .
- the perforation size of mesh disk 97 may vary.
- the mesh size of the perforations in the mesh disk is between approximately 0.5 mm and 3 mm.
- the mesh disk/filter 97 is a medical grade mesh filter disk, for example a metal mesh filter disk.
- the mesh disk/filter 97 includes a mesh disk support 98 to hold the mesh disk 97 in place in the compression tube 46 .
- tissue samples 9 are preferably placed directly into the compression tube 46 for processing.
- the tissue sample 9 is placed into a disposal mesh bag/sleeve 96 .
- the mesh size of the mesh bag 96 may vary. In some embodiments, the mesh size of the perforations for the mesh sleeve is between approximately 0.05 mm (5 microns) and 1 mm (1000 microns). In some embodiments, the mesh bag 96 is a disposable medical-grade mesh bag or sleeve.
- the mesh sleeve 96 in which the sample 9 has been placed is then placed within the compression tube 46 to contain the sample 9 during the compression process, as shown in FIG. 26 .
- the mesh sleeve 96 is a disposable medical-grade mesh bag or sleeve 96 .
- the mesh sleeve 96 may include a mesh base 99 .
- the mesh sleeve 96 may alternatively be used with the compression apparatus shown in FIGS. 1-14 .
- circular perforations 47 are shown in most of the figures, other shapes and patterns may alternatively used in any of the embodiments of the compression staging apparatuses described herein.
- the shape and size of the perforations in the compression tube 46 may be altered.
- FIGS. 28A through 28D show different embodiments for the perforations of a compression tube.
- FIG. 28A shows circular perforations 47 , as shown in the earlier figures.
- One example of a hole pattern is an 8 ⁇ 20 hole pattern.
- FIG. 28B shows slot perforations 49 .
- One example of a slot pattern is a 1 ⁇ 20 slot pattern. While the slot perforations 49 are arranged vertically in FIG. 28B , they may alternatively be arranged in another pattern.
- FIG. 28C shows spiral perforations 51 .
- One example of a spiral pattern is a 1 ⁇ 14 spiral pattern.
- the compression tube 106 has no perforations, as shown in FIG. 28D .
- This compression tube 106 could be used in combination with the mesh disk filter 97 shown in FIGS. 24 and 25 .
- the fat is extruded from the bottom of the compression tube 106 through the mesh disk filter 97 .
- the frame, compression assembly, extruded fat handling, and sample ejection is shown in the figures, the frame, compression assembly, fat containment and drainage sub-assembly, or ejection assembly could be a different shape, material, size, configuration, or layout to perform the same function within the spirit of the present invention.
- the compression force may alternatively be provided in any other manner, including, but not limited to, pneumatically, electrostatically, or mechanically. While hydraulic compression mechanisms are discussed herein, alternative compression mechanisms, including, but not limited to, linear actuators, motor driven screw jacks, pneumatic cylinders, solenoid cylinders, or arbor presses could alternatively be used.
- the compression force is shown as being monitored by a pressure gauge, the compression force may alternatively be monitored by any other force monitoring apparatus appropriate for the type of compression force being used, including, but not limited to, a pressure sensor, a force sensor, or a load cell.
- Automation may be introduced in the device, which complements the compression.
- an automated control system directs the compression process by actuating and controlling the output of the hydraulic pump while monitoring the position of the force actuator (for example, a hydraulic ram) and monitoring the compression force to perform the compression under predetermined conditions.
- the compression is done by the automated control system under predetermined compression force parameters to assure reproducibility between different samples.
- the parameters for the automated compression are selected for producing an optimum compressed sample for pathologic staging or other applications.
- the automated control system is integrated by way of a motor powering a force generator, which may include, but is not limited to, an electric hydraulic pump, a pneumatic/hydraulic pump, or a worm-gear driven screw jack.
- the motor is outfitted with a controller, which may be a pulse-width-modulation (PWM) style controller. After a relationship between the electrical current delivered to the motor and the mechanical force output of the motor is established, the controller is programmed to limit the maximum current delivered to the motor to a level that corresponds to the maximum desired ramming force.
- PWM pulse-width-modulation
- the maximum current/force in the system may be preset to a single fixed value or the system may allow the user to select a value from multiple present values or any value from within a spectrum of values bounded by a minimum and maximum value.
- the control system includes one or more sensors that allow the system to respond in real time to sample parameters, including, but not limited to, sample density, sample viscosity, and sample volume.
- FIG. 29 shows a block diagram of an example of an automated control system 100 for the compression device.
- the advanced control system 100 includes a microcontroller 140 which the user operates by means of a user interface 160 .
- the user interface 160 may be any user interface including, but not limited to, a digital display or a series of buttons.
- the microcontroller 140 provides information according to user instructions to a force applicator 105 .
- a force applicator 105 is the hydraulic ram 4 discussed above.
- Other examples of force applicators 105 include, but are not limited to, a pneumatic ram, a screw jack, or any other force-applying mechanism.
- the force applicator 105 applies force to the sample 9 and this process is monitored in real time by both a position sensor 120 , which detects the location of the force applicator 105 , and a force sensor 130 , which monitors the degree of force being applied 110 at any given moment.
- the information collected by these sensors 120 , 130 feeds back 150 into the microcontroller 140 , which uses this information to make adjustments to the operation of the force applicator 105 in accordance with user-generated settings.
- the sensors 120 , 130 signal to the microcontroller 140 that the use cycle is complete.
- the microcontroller 140 is also connected to a storage apparatus 170 , which is designed to store and deliver preset user settings as well as record data about each use cycle.
- This sample data 180 is retrievable for purposes of quality control monitoring. In the case of the medical application of this device, the data is “patient” sample data, 180 , but the sample data 180 could be any type of industry-specific sample data 180 .
- FIG. 30 shows a flow diagram of an example of a use cycle of the advanced control system 100 .
- the use cycle is initiated by powering on the pathologic staging device (PSD) in step 200 .
- PSD pathologic staging device
- the sample 9 is then loaded in the compression assembly (ASM) and secured in place in step 220 .
- the user selects the compression profile, or settings, via the user interface 160 in step 230 .
- the user then starts the compression in step 240 .
- the force applicator continues to advance 250 .
- the microcontroller 140 halts the motion of the force applicator 105 and saves the force and position data from this compression cycle to the storage device 170 in step 330 .
- the force applicator 105 is then retracted to the home position in step 340 , after which the sample 9 is removed from the compression assembly in step 350 .
- the next step is either to power down the unit (step 360 ) or load a new sample in the compression assembly (step 370 ) and repeat the process (step 380 ), beginning with the select compression profile step 230 .
- the compression apparatus is described herein for use on tissue samples for staging cancer, the compression device could alternatively used in any applications where fatty tissue needs to be separated. Some examples include gynecological, breast, and other areas of the body with fatty tissues. Other surgical disciplines where fatty tissue can be collected may also find the compression apparatus helpful to decrease time throughout the process of resection (including any type of surgical resection including, but not limited to, abdnominal resections) and pathologic staging. A surgical oncologist may change their process for surgical resection to incorporate the compression devices described herein. Using the compression apparatuses described herein on these types of tissues decreases specimen pathology testing time. In addition, the compression apparatus could be used on other types of samples, including, but not limited to, food samples, botanical samples, and artificial substances.
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Abstract
A pathologic staging compression device prepares a biological sample for pathologic staging by compressing the sample to remove liquid fat from the sample. In one embodiment, the apparatus preferably includes a compression tube, a removable drainage planum to hold the compression tube, a fat containment and drainage system, a gauge to monitor the extrusion force, use of hydraulic pressure to generation the extrusion force for sample compression, and ejection of the compressed sample after the compression tube has been removed from the drainage planum. In another embodiment, the apparatus includes an integrated riser assembly to stabilize and align the compression tube.
Description
- This application claims one or more inventions which were disclosed in Provisional Application No. 62/160,003, filed May 12, 2015, entitled “PATHOLOGIC STAGING COMPRESSION APPARATUS AND METHODS”. The benefit under 35 USC § 119(e) of the United States provisional application is hereby claimed, and the aforementioned application is hereby incorporated herein by reference.
- The invention pertains to the field of pathologic staging. More particularly, the invention pertains to apparatus and methods for preparing a biological sample for pathologic staging.
- The pathologic stage is an essential piece of diagnostic information which is used to determine a cancer patient's prognosis and treatment, including whether or not the patient will receive chemotherapy.
- To determine the pathologic stage of colorectal cancer, the surgeon first resects a section of fatty tissue from the patient's abdomen. This fatty tissue is then sent to the surgical pathologist, whose responsibility is to determine the stage of the illness based on the extent of cancer observed within this tissue. Importantly, the pathologist is not interested in the fat itself, but rather in the fibrous tissue and lymph nodes that are contained within the fatty tissue.
- Conventionally, the pathologist meticulously dissects the fatty tissue with a scalpel in search of fibrous material and lymph nodes. The pathologist removes any clearly visible nodes or other relevant fibrous tissue for examination under the microscope. Inevitably, however, some very small or microscopic pieces of tissue are left behind, but the presence or absence of any diagnostically relevant information (which may be microscopic) within the resected tissue may change the patient's prognosis and treatment. To account for this, the pathologist conventionally selects five to ten random samples from the tissue for microscopic study.
- In recent years, a team of pathologists in Germany has pioneered a technique that makes this process both more efficient and more accurate (see, for example, Gehoff et al., Am. J. Surg. Pathol., Vol. 36, pp. 202-213, 2012; Basten et al., Pathologe, Vol. 31, pp. 218-224, 2010; and Scheel et al., “Comprehensive lymph node morphometry in rectal cancer using acetone compression”, J. Clin. Pathol., e-published Mar. 16, 2015). Referred to as the “acetone compression method” (ACM), this method allows the pathologist to eliminate the time-consuming dissection process while simultaneously avoiding the risk of missing diagnostically relevant tissue.
- In brief, the methodology is as follows:
- 1. When the pathologist receives the resected fatty tissue in the laboratory, he/she first examines it for any large and clearly-visible pieces of diagnostically-relevant tissue.
- 2. The pathologist then slices the sample into small (2 to 3 mm) sections and puts this material in acetone to soak overnight. Acetone dissolves lipids without affecting the integrity of fibrous tissue.
- 3. The following day, the tissue is removed from the acetone bath and loaded into a specialized tube that is perforated with small (1 to 2 mm diameter) holes.
- 4. An arbor press, which is a mechanical device using a rack and pinion gear to exert a linear force, is then used to compress the sample in the tube. Compressing the sample forces the fatty components to be extruded out of the small holes in the tube.
- 5. After compression is complete, the only portions of the original sample remaining within the tube are the fibrous components of that tissue. The pathologist has therefore eliminated all diagnostically irrelevant information, i.e. fat, from the tissue sample.
- ACM represents a more time-efficient approach for processing the tissue than conventional hand dissection. In addition, ACM eliminates the risk that the pathologist may overlook diagnostically relevant information, therefore increasing the accuracy of the pathologic staging process for cancers of this type.
- Lymph nodes are usually the first organs invaded by malignant cells when they metastasize from the primary tumor site. The determination of the presence or absence of metastases in local lymph nodes is critical in determining the prognosis and treatment of the patient. ACM is capable of providing double or even quadruple the number of lymph nodes, compared to the conventional technique of tedious dissection. Not only does ACM relieve the pathologist of most of this dissection, it does a better job by allowing the fat to be processed in an economical and practical manner.
- The above-mentioned references are hereby incorporated by reference herein.
- In one embodiment, a pathologic staging compression device prepares a biological sample for pathologic staging by compressing the sample to remove liquid fat from the sample. In one embodiment, the apparatus preferably includes a compression tube with flange and a clamping plate to stabilize and align the compression tube, a fat containment and drainage system, a gauge to monitor the extrusion force, use of hydraulic pressure to generate the extrusion force for sample compression, and integrated ejection of the compressed sample and plunger.
- In another embodiment, the apparatus preferably includes a compression tube, a drainage planum to hold and align the compression tube, a fat containment and drainage system, a gauge to monitor the extrusion force, use of hydraulic pressure to generate the extrusion force for sample compression, and ejection of the compressed sample after the compression tube has been removed from the drainage planum.
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FIG. 1 shows an isometric view of a pathologic staging compression apparatus in an embodiment of the present invention. -
FIG. 2 shows a front view of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 3 shows a side view of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 4 shows an isometric view of the compression assembly of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 5 shows a front view of the compression assembly ofFIG. 4 . -
FIG. 6 shows a side view of the compression assembly ofFIG. 4 . -
FIG. 7 shows an exploded view of the compression assembly ofFIG. 4 . -
FIG. 8 shows an exploded view of the fat containment and drainage sub-assembly of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 9 shows an exploded view of the compression tube sub-assembly of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 10 shows an exploded view of the riser plate sub-assembly of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 11 shows an isometric view of the compression tube of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 12 shows a side view of the compression tube ofFIG. 11 . -
FIG. 13 shows a cross sectional view of the fat containment and drainage system of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 14 shows a partial cross sectional view of the compression system of the pathologic staging compression apparatus ofFIG. 1 . -
FIG. 15 shows another embodiment of a pathologic staging compression apparatus. -
FIG. 16 shows a front view of the pathologic staging compression apparatus ofFIG. 15 . -
FIG. 17 shows a side view of the pathologic staging compression apparatus ofFIG. 15 . -
FIG. 18A shows a view of the removable drainage planum in the compression assembly. -
FIG. 18B shows a top view of the removable drainage planum in the compression assembly. -
FIG. 18C shows a drainage plug that may be used in combination with the drainage planum ofFIGS. 18A and 18B . -
FIG. 19 shows the compression tube and the removable drainage planum. -
FIG. 20 shows a hand plunger to be used with the apparatus. -
FIG. 21 shows an assembly of the hand plunger and compression tube on the bottom plug. -
FIG. 22 shows the pathologic staging compression apparatus with the drainage planum in an embodiment of the invention. -
FIG. 23A shows detail of the magnet and pins fromcircle 23 ofFIG. 22 . -
FIG. 23B shows detail of the magnet and pins fromcircle 23 ofFIG. 22 . -
FIG. 24A shows an embodiment with a mesh filter/disk and a compression tube. -
FIG. 24B shows a top view of the embodiment ofFIG. 24A . -
FIG. 24C shows another view of the embodiment ofFIG. 24A . -
FIG. 25 shows a mesh/disk filter. Perforation size of the mesh disk may vary. -
FIG. 26 shows an embodiment with a mesh sleeve or bag and a compression tube. Perforation size of the mesh sleeve or bag may vary. -
FIG. 27A shows a view of the mesh sleeve or bag ofFIG. 26 , which may include a mesh base. -
FIG. 27B shows another view of the mesh sleeve or bag ofFIG. 26 . -
FIG. 28A shows a compression tube with a 8×20 hole pattern. -
FIG. 28B shows a compression tube with a 1×20 slot pattern. -
FIG. 28C shows a compression tube with a 1×14 spiral pattern. -
FIG. 28D shows a compression tube with no perforations. -
FIG. 29 shows a block diagram of an example of an automated control system for the compression device. -
FIG. 30 shows a flow diagram of a use cycle of an automated control system for the compression device. - Although the acetone compression method (ACM) was initially described for colon carcinomas, it may be useful in other cancer situations as well, where there is a need to examine fat for evidence of lymph nodes or microscopic deposits of tumor, such as a resected omentum in certain cases of gynecological malignancies. In preliminary testing of a pathologic staging compression apparatus of the present invention, the apparatus was found to be useful in preparing samples for pathologic staging of ovarian cancer in addition to colorectal cancer. In addition to simplifying lymph node examination for various surgical cancer specimens, ACM standardizes and dramatically increases the sensitivity of the pathologic staging process.
- A pathologic staging compression apparatus preferably allows surgical pathologists to determine the pathologic stage of certain cancers, including, but not limited to, colorectal, breast, sarcoma, soft tissue and ovarian cancers, with greater accuracy and efficiency than is possible with conventional methods and apparatus. The compression apparatus may be used to pathologically stage any cancer where fatty tissue is present. Use of this apparatus as part of ACM preferably provides higher quality samples for pathologic staging. Any resected fatty tissue mass, human or animal, which is sent to a pathologist may utilize acetone treatment and the compression apparatuses described herein.
- The pathologic stage, an essential piece of diagnostic information, is used to determine a cancer patient's prognosis and treatment, including whether or not the patient will receive chemotherapy. Better pathologic staging can help a clinician determine the best chemotherapy dosage for each individual patient. A directed, specific and measured dose of chemotherapy can be individually tailored to the patient based on the diagnostic result indicated in pathologic staging.
- Replicating the published ACM as it was described in the literature resulted in the method working as described in the published literature. Many key areas for improving the process were noted, however, from an ease-of-use, safety, accuracy, reliability, and standardization standpoint. A pathologic staging compression apparatus was developed as a result of deficiencies in the prior art apparatus.
- A pathologic staging compression apparatus preferably includes a tube flange and a clamping plate for stabilization and alignment of the compression tube, a fat containment and drainage system, monitoring of the extrusion force being applied, use of hydraulic force for generation of the extrusion force for sample compression, and integrated ejection of the sample and plunger as improvements to the prior art apparatus. Being able to measure and monitor the extrusion pressure or extrusion force is essential to standardizing sample processing.
- A pathologic staging compression apparatus preferably allows surgical pathologists to perform ACM with greater ease, safety, accuracy, reliability, and replicability than the prior art device described in the academic literature.
- In a preferred embodiment, a frame of the pathologic staging compression apparatus supports a hydraulic ram held in alignment with the compression tube of a compression assembly on the frame. A pressure gauge/sensor measures the pressure of the hydraulic fluid being used to actuate the hydraulic ram. A measurement of the force exerted onto the tissue sample can be extrapolated from this value. The compression tube is mounted on a clamping plate between two flanges on the compression tube. The compression tube includes an array of small through-holes through the cylindrical wall of the compression tube. The clamping plate aligns the compression tube with the hydraulic ram and prevents movement of the compression tube during a compression cycle. The clamping plate is mounted onto a riser plate by way of a pair of thumb nuts. The riser plate is mounted to the frame.
- In a preferred method of preparing a tissue sample for pathologic staging, the tissue sample presoaked in acetone is placed in the compression tube with the bottom plug press-fit into the bottom of the compression tube. Optionally, a shield is mounted around the compression tube as part of a liquid fat containment system. The compression tube is mounted onto the clamping plates and the plunger is placed on top of the compression tube. Slots in the clamping plates allow the clamping plates to slide between an engaged position and a retracted position. In the engaged position, the clamping plates are slid firmly against the exterior diameter of the compression tube and the thumb nuts are tightened. In the retracted position, the compression plates, slidable when the thumb nuts are loosened, are slid laterally away from the compression tube. In the course of a single operation cycle, the operator places the compression tube on top of the riser plate with the clamping plates in the retracted position. The operator then slides the clamping plates towards the compression tube until they are firmly pressed against the exterior diameter of the compression tube before locking the thumb nuts. This action preferably automatically locates the compression tube on-center in relation to the hydraulic ram; no further adjustment beyond sliding the clamping plates inward and tightening the thumb nuts is necessary.
- Optionally, a jack is actuated to raise the compression sub-assembly in the frame until the plunger contacts the hydraulic ram. The hydraulic pump is then actuated to drive the hydraulic ram to compress the tissue sample. Optionally, after compression of the sample is complete, a stop block below the compression tube is removed and the hydraulic ram is further driven to push the bottom plug out the bottom of the compression tube.
- Optionally, the bottom plug is then removed and the hydraulic ram is further driven to eject the compressed sample from the bottom of the compression tube. When the operator desires to remove the compression tube, the thumb nuts are loosened and the clamping plates are slid into the retracted position, after which the tube can be lifted off the riser plate.
- In another preferred embodiment, the riser plate sub assembly of the frame of the pathologic staging compression apparatus is replaced by a drainage planum or platform. The bottom plug is permanently fixed onto the drainage planum in this embodiment. Unlike the riser plate sub-assembly, the drainage planum is preferably removed from the frame of the device during each use cycle.
- In a method of preparing a tissue sample for pathologic staging, the user first removes the drainage planum from the frame of the device. The user then places the compression tube onto the drainage planum using the bottom plug affixed to the drainage planum. The tissue sample presoaked in acetone is then placed in the compression tube and preferably subject to an initial hand compression using a hand plunger. Optionally, a shield is placed around the compression tube, its base resting on the surface of the drainage planum as part of a liquid fat containment system. Any fat extruded during the initial hand compression is drawn out of the drainage planum via an integrated drainage hole. Following initial hand compression, the drainage planum is then mounted onto the frame of the device. The drainage planum is preferably located on the frame using locating pins and held in place by fasteners, such as magnets (for example neodymium magnets). Removal of the sample from the device occurs by first removing the compression tube from the drainage planum. The sample is then ejected from the compression tube using a hand plunger.
- In some embodiments, instead of tissue samples being placed directly into the compression tube, the tissue samples are placed in a disposable medical grade mesh bag/sleeve. The sleeve is then placed into the compression tube for processing. The use of mesh sleeves simplify cleaning of the compression tube. In other embodiments, a mesh disk/filter acts as the bottom of the compression tube.
- The shape and size of the perforations in the compression tube may vary. For example, to accommodate the use of the mesh sleeves or disks, the perforations may be designed to work in conjunction with these mesh devices. In some embodiments, the width/diameter of the perforations may increase and the shape may change from circular perforations to slit-shaped perforations. These slit-shaped perforations may be arranged vertically along the circumference of the compression tube or arranged in some other manner, such as an involute spiral pattern. In embodiments with a mesh disk filter acting as the bottom of the compression tube, the compression tube may lack perforations entirely.
- The hydraulic pump of the compression staging apparatus may be mounted directly onto the frame of the device or not mounted directly onto the frame of the device.
- Referring to
FIG. 1 throughFIG. 6 , the pathologicstaging compression apparatus 10 includes aframe 6, ahydraulic ram 4, ahydraulic hose 12, ahydraulic pump 14, apressure gauge 2, and acompression assembly 8. Theframe 6 supports and positions thehydraulic cylinder 4 and thecompression tube 46. Thehydraulic ram 4 provides a compression force to compress asample 9 in thecompression assembly 8. Thehydraulic hose 12 delivers hydraulic oil from thehydraulic pump 14 to thehydraulic ram 4. Thehydraulic pump 14 actuates thehydraulic ram 4. Thepressure gauge 2 registers and displays the hydraulic pressure. - The
compression assembly 8 includes aperforated compression tube 46, a fat containment tube orshield 16, a clampingplate 22, ariser plate 24, fasteners 28 (for example, thumb nuts), astop block 26, and adrainage tube 20. Theshield 16 is preferably made of a clear plastic material. In one preferred embodiment, theshield 16 is made of polycarbonate. Referring toFIG. 7 , thecompression assembly 8 includes a fat containment anddrainage sub-assembly 30, acompression tube sub-assembly 40, and ariser plate sub-assembly 60. - Referring to
FIG. 8 , the fat containment anddrainage sub-assembly 30 includes theclear plastic shield 16 to contain the extruded liquid fat from thesample 9, a mountingplate 34 to support theclear plastic shield 16 and provide a drainage hole 36 (seeFIG. 13 ) for drainage of the fat, an o-ring 32 to provide a liquid tight seal between theclear plastic shield 16 and the mountingplate 34, and thedrainage tube 20 receiving the drained liquid fat from thedrainage hole 36 in the mountingplate 34 and directing the drained liquid fat. - Referring to
FIG. 9 , thecompression tube sub-assembly 40 includes aplunger 42 to compress the sample in thecompression tube 46, an o-ring 44 to provide a liquid tight seal between thecompression tube 46 and the mountingplate 34 for theclear plastic shield 16, thecompression tube 46 in the form of a perforated 47compression vessel 46 that contains thesample 9 and allows for extrusion of liquid fat through theperforations 47, and abottom plug 48 to seal the opening at the bottom of thecompression tube 46 during compression. - Referring to
FIG. 10 , theriser plate sub-assembly 60 includes ariser plate 24 to provide a platform for thecompression tube 46, astop block 26 to hold thebottom plug 48 in position during compression, clampingplates 22 to stabilize and secure thecompression tube 46, and a pair of fasteners 28 (for example, thumb nuts) to lock theclamping plates 22 and thereby secure thecompression tube 46. - Referring to
FIG. 11 andFIG. 12 , liquid fat is extruded outsmall perforations 47 in thecompression tube 46. In some embodiments, thecompression tube 46 has an interior space in the range of 1.2 to 12 cubic inches (20 to 200 cubic centimeters) in volume to receive a sample. The volume of thecompression tube 46 varies depending on the size of the sample being treated. The size and number of perforations are selected to be large enough for liquid fat to pass through them, but small enough that fibrous tissue cannot. In some embodiments, the perforations are about 3/64″ (1.2 mm) in diameter. An o-ring seating groove 52 provides a seat for the o-ring 44 forming a seal between thecompression tube 46 and theclear plastic shield 16. Aflange 54 along the lower edge of thetube 46 allows for stabilization and alignment of thecompression tube 46 when used in conjunction with the clampingplates 22. Asecondary flange 56 allows for the mounting of the fat containment anddrainage sub-assembly 30 onto thecompression tube 46. - Referring to
FIG. 13 , theplunger 42 and thebottom plug 48 seal the top and bottom of thecompression tube 46, respectively, to maintain the sample within thecompression tube 46 during compression. The o-rings 44 seal the mountingplate 34 with respect to theclear plastic shield 16 and thecompression tube 46 such that the liquid fat extruded from thecompression tube 46 drains out thedrainage hole 36. Thedrainage tube 20 mounts on atubing barb 38 extending from the bottom of the mountingplate 34. - Referring to
FIG. 14 , thehydraulic ram 4 aligns with the opening in the top of thecompression tube 46 and contacts and drives theplunger 42 downward to compress thesample 9 in thecompression tube 46 using the hydraulic force generated by thehydraulic pump 14. When a predetermined compression has been achieved, thesample 9 is preferably ejected by removing thestop block 26 from below thebottom plug 48 and then actuating thehydraulic ram 4 farther in the direction ofactuation 70 until thebottom plug 48 is driven out the bottom of thecompression tube 46 and into the space previously occupied by thestop block 26, where it may be easily removed from the apparatus by the user. Thecompressed sample 9 is then driven out the bottom of thecompression tube 46 and into the space previously occupied by thestop block 26, where it may be removed by hand either before or after sliding the clampingplates 22 to the retracted position and lifting thecompression tube sub-assembly 40 off theriser plate 24. - In an alternative embodiment, shown in
FIGS. 15-17, 22, 23A and 23B , theriser plate subassembly 60 shown in the embodiment ofFIGS. 1-14 is replaced by aremovable drainage planum 81. In this embodiment, the bottom plug 82 (seeFIG. 19 ) is permanently fixed onto thedrainage planum 81. Unlike in embodiments with ariser plate subassembly 60, thedrainage planum 81 is preferably designed to be removed from theframe 6 of thecompression staging apparatus 80 during each use cycle. - Details of the
bottom plug 82, drainage planum 81 andcompression tube 46 of thecompression assembly 85 are shown inFIGS. 18-21 . During a given use cycle, the user first removes thedrainage planum 81 and the bottom plug 82 from theframe 6 of thecompression staging apparatus 80. Thecompression tube 46 is then placed onto the drainage planum 81 using thebottom plug 82 affixed to thedrainage planum 81. Thetissue sample 9 is then loaded into thecompression tube 46 and preferably given an initial hand compression in the direction of thearrow 92 inFIG. 21 using ahand plunger 90. In some embodiments, the hand plunger is made of an acetal resin. Any fat extruded during an initial hand compression drains out of the drainage planum 81 via anintegrated drainage hole 83, shown inFIG. 18B . Adrainage plug 93, which is shaped to fit into and plug thedrainage hole 83 when inserted into thedrainage hole 83, is shown inFIG. 18C . - Following the initial hand compression (or as the primary compression step if the user decides not to perform an initial hand compression), the
drainage planum 81 is then mounted onto theframe 6 of thecompression staging apparatus 80. In some preferred embodiments, thedrainage planum 81 is reversibly affixed to theframe 6 using locating pins 84 and locating pin holes 89 and held in place bymagnets FIGS. 22, 23A and 23B . Aplanum alignment plate 91 aids in affixing theframe 6 to thedrainage planum 81. - In the embodiment shown in
FIGS. 15-22 , ejection of the sample occurs by first removing thecompression tube 46 from thedrainage planum 81. Thesample 9 is then preferably ejected from thecompression tube 46 using ahand plunger 90. In the embodiments shown inFIGS. 1-14 , thesample 9 is preferably ejected from thecompression tube 46 using thestop block 26. - In the embodiments shown in
FIGS. 15-22 , theshield 16 is preferably placed around thecompression tube 46, with the base of theshield 16 resting on a surface of thedrainage planum 81. In the embodiments shown inFIGS. 1-14 , theshield 16 that contains the spray from the extrusion of liquefied fat is preferably mounted directly onto thecompression tube 46 using the mountingplate 34, as shown inFIG. 8 . - In some embodiments, the hydraulic pump is not mounted directly on the device (for example in the
apparatus 10 shown inFIGS. 1-14 ). In alternative embodiments, thehydraulic pump 88 is mounted directly onto theframe 6 of theapparatus 80, as shown inFIG. 15 . - In another embodiment, the
bottom plug mesh disk filter 97, as shown inFIGS. 24 and 25 . Using amesh disk filter 97 for thebottom plug compression tube 46, in addition to or instead of through theperforations 47 in thecompression tube 46. This permits the use of a compression tube that has no holes or perforations, as shown inFIG. 28D . The perforation size ofmesh disk 97 may vary. In some embodiments, the mesh size of the perforations in the mesh disk is between approximately 0.5 mm and 3 mm. In some embodiments, the mesh disk/filter 97 is a medical grade mesh filter disk, for example a metal mesh filter disk. The mesh disk/filter 97 includes amesh disk support 98 to hold themesh disk 97 in place in thecompression tube 46. - In the embodiments described above,
tissue samples 9 are preferably placed directly into thecompression tube 46 for processing. In alternative embodiments, shown inFIGS. 26-27 , thetissue sample 9 is placed into a disposal mesh bag/sleeve 96. The mesh size of themesh bag 96 may vary. In some embodiments, the mesh size of the perforations for the mesh sleeve is between approximately 0.05 mm (5 microns) and 1 mm (1000 microns). In some embodiments, themesh bag 96 is a disposable medical-grade mesh bag or sleeve. - In these embodiments, the
mesh sleeve 96 in which thesample 9 has been placed is then placed within thecompression tube 46 to contain thesample 9 during the compression process, as shown inFIG. 26 . These embodiments simplify the cleaning of thecompression tube 46. In some embodiments, themesh sleeve 96 is a disposable medical-grade mesh bag orsleeve 96. Themesh sleeve 96 may include amesh base 99. Themesh sleeve 96 may alternatively be used with the compression apparatus shown inFIGS. 1-14 . - While
circular perforations 47 are shown in most of the figures, other shapes and patterns may alternatively used in any of the embodiments of the compression staging apparatuses described herein. For example, to accommodate the use of a mesh bag/sleeve or mesh disk filter with thecompression tube 46, the shape and size of the perforations in thecompression tube 46 may be altered. -
FIGS. 28A through 28D show different embodiments for the perforations of a compression tube.FIG. 28A showscircular perforations 47, as shown in the earlier figures. One example of a hole pattern is an 8×20 hole pattern.FIG. 28B showsslot perforations 49. One example of a slot pattern is a 1×20 slot pattern. While theslot perforations 49 are arranged vertically inFIG. 28B , they may alternatively be arranged in another pattern.FIG. 28C showsspiral perforations 51. One example of a spiral pattern is a 1×14 spiral pattern. - Other geometric or free form shapes for the perforations could alternatively be used. The number of perforations, the arrangement of the perforations, the width of the perforations, and/or the diameter of the perforations using any of the shapes described above also may vary.
- In some embodiments, the
compression tube 106 has no perforations, as shown inFIG. 28D . Thiscompression tube 106 could be used in combination with themesh disk filter 97 shown inFIGS. 24 and 25 . In these embodiments, the fat is extruded from the bottom of thecompression tube 106 through themesh disk filter 97. - Although specific designs for the frame, the compression assembly, extruded fat handling, and sample ejection is shown in the figures, the frame, compression assembly, fat containment and drainage sub-assembly, or ejection assembly could be a different shape, material, size, configuration, or layout to perform the same function within the spirit of the present invention.
- Although a hydraulic pump is shown as supplying the compression force, the compression force may alternatively be provided in any other manner, including, but not limited to, pneumatically, electrostatically, or mechanically. While hydraulic compression mechanisms are discussed herein, alternative compression mechanisms, including, but not limited to, linear actuators, motor driven screw jacks, pneumatic cylinders, solenoid cylinders, or arbor presses could alternatively be used.
- Although the compression force is shown as being monitored by a pressure gauge, the compression force may alternatively be monitored by any other force monitoring apparatus appropriate for the type of compression force being used, including, but not limited to, a pressure sensor, a force sensor, or a load cell.
- Automation may be introduced in the device, which complements the compression. In some embodiments, an automated control system directs the compression process by actuating and controlling the output of the hydraulic pump while monitoring the position of the force actuator (for example, a hydraulic ram) and monitoring the compression force to perform the compression under predetermined conditions. In some embodiments, the compression is done by the automated control system under predetermined compression force parameters to assure reproducibility between different samples. In a preferred embodiment, the parameters for the automated compression are selected for producing an optimum compressed sample for pathologic staging or other applications.
- In some embodiments, the automated control system is integrated by way of a motor powering a force generator, which may include, but is not limited to, an electric hydraulic pump, a pneumatic/hydraulic pump, or a worm-gear driven screw jack. The motor is outfitted with a controller, which may be a pulse-width-modulation (PWM) style controller. After a relationship between the electrical current delivered to the motor and the mechanical force output of the motor is established, the controller is programmed to limit the maximum current delivered to the motor to a level that corresponds to the maximum desired ramming force. The maximum current/force in the system may be preset to a single fixed value or the system may allow the user to select a value from multiple present values or any value from within a spectrum of values bounded by a minimum and maximum value. In some embodiments, the control system includes one or more sensors that allow the system to respond in real time to sample parameters, including, but not limited to, sample density, sample viscosity, and sample volume.
-
FIG. 29 shows a block diagram of an example of anautomated control system 100 for the compression device. As shown inFIG. 29 , theadvanced control system 100 includes amicrocontroller 140 which the user operates by means of auser interface 160. - The
user interface 160 may be any user interface including, but not limited to, a digital display or a series of buttons. Themicrocontroller 140 provides information according to user instructions to aforce applicator 105. One example of aforce applicator 105 is thehydraulic ram 4 discussed above. Other examples offorce applicators 105 include, but are not limited to, a pneumatic ram, a screw jack, or any other force-applying mechanism. Theforce applicator 105 applies force to thesample 9 and this process is monitored in real time by both aposition sensor 120, which detects the location of theforce applicator 105, and aforce sensor 130, which monitors the degree of force being applied 110 at any given moment. The information collected by thesesensors microcontroller 140, which uses this information to make adjustments to the operation of theforce applicator 105 in accordance with user-generated settings. When thesample 9 has been compressed to the degree indicated by the user, thesensors microcontroller 140 that the use cycle is complete. Themicrocontroller 140 is also connected to astorage apparatus 170, which is designed to store and deliver preset user settings as well as record data about each use cycle. Thissample data 180 is retrievable for purposes of quality control monitoring. In the case of the medical application of this device, the data is “patient” sample data, 180, but thesample data 180 could be any type of industry-specific sample data 180. -
FIG. 30 shows a flow diagram of an example of a use cycle of theadvanced control system 100. The use cycle is initiated by powering on the pathologic staging device (PSD) instep 200. This begins a process by which theforce applicator 105 is returned to its home position instep 210. Thesample 9 is then loaded in the compression assembly (ASM) and secured in place instep 220. The user then selects the compression profile, or settings, via theuser interface 160 instep 230. The user then starts the compression instep 240. This signals theforce applicator 105 to advance one unit instep 250, simultaneously triggering theforce sensor 130 andpressure sensor 140 to monitor the progress of theforce applicator 105 insteps steps step 320, themicrocontroller 140 halts the motion of theforce applicator 105 and saves the force and position data from this compression cycle to thestorage device 170 instep 330. Theforce applicator 105 is then retracted to the home position instep 340, after which thesample 9 is removed from the compression assembly instep 350. The next step is either to power down the unit (step 360) or load a new sample in the compression assembly (step 370) and repeat the process (step 380), beginning with the selectcompression profile step 230. - Although a pathologic staging compression apparatus has been used for staging of colorectal cancer and ovarian cancer, further use and adoption of the apparatus is expected to lead to additional diagnostic applications where separating tissues of different densities is advantageous.
- While the compression apparatus is described herein for use on tissue samples for staging cancer, the compression device could alternatively used in any applications where fatty tissue needs to be separated. Some examples include gynecological, breast, and other areas of the body with fatty tissues. Other surgical disciplines where fatty tissue can be collected may also find the compression apparatus helpful to decrease time throughout the process of resection (including any type of surgical resection including, but not limited to, abdnominal resections) and pathologic staging. A surgical oncologist may change their process for surgical resection to incorporate the compression devices described herein. Using the compression apparatuses described herein on these types of tissues decreases specimen pathology testing time. In addition, the compression apparatus could be used on other types of samples, including, but not limited to, food samples, botanical samples, and artificial substances.
- Accordingly, it is to be understood that the embodiments of the invention herein described are merely illustrative of the application of the principles of the invention. Reference herein to details of the illustrated embodiments is not intended to limit the scope of the claims, which themselves recite those features regarded as essential to the invention.
Claims (69)
1. A compression device comprising:
a frame;
a hydraulic ram held by the frame;
a hydraulic pump providing pressurized hydraulic fluid to the hydraulic ram to actuate the hydraulic ram;
a pressure sensor measuring a hydraulic pressure of the pressurized hydraulic fluid;
a compression tube mounted and held in the frame in alignment with the hydraulic ram, the compression tube comprising a cylindrical side wall and defining a cylindrical space between a top open end and a bottom open end for receiving a sample, the cylindrical side wall having a plurality of through-holes;
a bottom plug received in the bottom open end of the compression tube;
wherein actuation of the hydraulic ram by the hydraulic pump actuates the hydraulic ram to compress a sample in the cylindrical space between the hydraulic ram and the bottom plug.
2. The compression device of claim 1 , further comprising a cylindrical shield placed around the compression tube.
3. The compression device of claim 2 , wherein the cylindrical shield is made of plastic.
4. The compression device of claim 2 , further comprising a mounting plate having a hole and a seal between the mounting plate and the cylindrical shield, wherein the cylindrical shield is mounted on the mounting plate.
5. The compression device of claim 4 , further comprising a drainage tube extending from the hole of the mounting plate.
6. The compression device of claim 4 , further comprising a plunger in the compression tube, and a seal between the compression tube and the mounting plate.
7. The compression device of claim 4 , further comprising a first flange along a lower edge of the compression tube and a second flange that mounts the mounting plate onto the compression tube.
8. The compression device of claim 1 , further comprising a plunger in the compression tube.
9. The compression device of claim 1 , further comprising a drainage planum, wherein the bottom plug is permanently affixed to the drainage planum.
10. The compression device of claim 9 , wherein the drainage planum, the bottom plug and the compression tube form a compression assembly that is removable from the frame of the compression device.
11. The compression device of claim 9 , further comprising a mesh sleeve that fits into the compression tube and holds the sample.
12. The compression device of claim 9 , wherein the bottom plug comprises a mesh filter disk.
13. The compression device of claim 9 , wherein the bottom plug is removable from the bottom of the compression tube.
14. The compression device of claim 1 , further comprising a stop block located below the bottom plug, at least one clamping plate shaped to fit around the compression tube, and a riser plate platform located under the clamping plate and surrounding the stop block, the clamping plate securing the compression tube to the riser plate platform using fasteners.
15. The compression device of claim 1 , wherein the compression tube has a volume between approximately 1.2 to 12 cubic inches.
16. The compression device of claim 1 , wherein the through-holes in the compression tube are approximately 3/64″ in diameter.
17. The compression device of claim 1 , wherein the through-holes have a shape selected from the group consisting of round perforations, slit perforations and spiral perforations.
18. The compression device of claim 1 , wherein the hydraulic pump is mounted directly on the frame.
19. The compression device of claim 1 , further comprising a mesh sleeve that fits into the compression tube and holds the sample.
20. The compression device of claim 19 , wherein the bottom plug comprises a mesh filter disk.
21. The compression device of claim 1 , wherein the bottom plug is permanently mounted in the bottom of the compression tube.
22. The compression device of claim 1 , wherein the bottom plug is reversibly mounted in the bottom of the compression tube.
23. The compression device of claim 1 , wherein the compression device is a pathologic staging compression device.
24. The compression device of claim 1 , further comprising an automated control system that directs a compression process by actuating and controlling an output of the hydraulic pump while monitoring a position of the hydraulic ram and monitoring a compression force to perform compression under predetermined conditions.
25. A compression device comprising:
a frame;
a compression tube mounted and held in the frame, the compression tube comprising a cylindrical side wall and defining a cylindrical space between a top open end and a bottom open end for receiving a sample, the cylindrical side wall having a plurality of through-holes;
a bottom plug received in the bottom of the compression tube;
a cylindrical shield shaped to fit around the compression tube and contain any fat that is removed from the sample during compression; and
a compression mechanism to compress the sample in the cylindrical space of the compression tube.
26. The compression device of claim 25 , wherein the cylindrical shield is made of plastic.
27. The compression device of claim 25 , further comprising a mounting plate having a hole and a seal between the mounting plate and the cylindrical shield, wherein the cylindrical shield is mounted on the mounting plate.
28. The compression device of claim 27 , further comprising a drainage tube extending from the hole of the mounting plate to drain fat from the compression tube.
29. The compression device of claim 27 , further comprising a plunger in the compression tube, and a seal between the compression tube and the mounting plate.
30. The compression device of claim 27 , further comprising a first flange along a lower edge of the compression tube and a second flange that mounts the mounting plate onto the compression tube.
31. The compression device of claim 25 , wherein the compression mechanism comprises:
a hydraulic ram held by the frame, the hydraulic ram being aligned with the compression tube;
a hydraulic pump providing pressurized hydraulic fluid to the hydraulic ram to actuate the ram; and
a pressure sensor measuring a hydraulic pressure of the pressurized hydraulic fluid;
wherein actuation of the hydraulic ram by the hydraulic pump drives the hydraulic ram into the cylindrical space to compress the sample in the cylindrical space between the hydraulic ram and the bottom plug.
32. The compression device of claim 31 , wherein the hydraulic pump is mounted directly on the frame.
33. The compression device of claim 25 , further comprising a plunger in the compression tube.
34. The compression device of claim 25 , further comprising a drainage planum, wherein the bottom plug is permanently affixed to the drainage planum.
35. The compression device of claim 34 , wherein the drainage planum, the bottom plug and the compression tube form a compression assembly that is removable from the frame of the pathologic staging compression device.
36. The compression device of claim 34 , wherein the bottom plug is removable from the bottom of the compression tube.
37. The compression device of claim 34 , further comprising a mesh sleeve that fits into the compression tube and holds the sample.
38. The compression device of claim 37 , wherein the bottom plug comprises a mesh filter disk.
39. The compression device of claim 25 , further comprising a stop block located below the bottom plug, at least one clamping plate shaped to fit around the compression tube, and a riser plate platform located under the clamping plate and surrounding the stop block, the clamping plate securing the compression tube to the riser plate platform using fasteners.
40. The compression device of claim 25 , wherein the compression tube has a volume between approximately 1.2 to 12 cubic inches.
41. The compression device of claim 25 , wherein the through-holes in the compression tube are approximately 3/64″ in diameter.
42. The compression device of claim 25 , wherein the through-holes have a shape selected from the group consisting of round perforations, slit perforations and spiral perforations.
43. The compression device of claim 25 , further comprising a mesh sleeve that fits into the compression tube and holds the sample.
44. The compression device of claim 25 , wherein the bottom plug comprises a mesh filter disk.
45. The compression device of claim 25 , wherein the bottom plug is permanently mounted in the bottom of the compression tube.
46. The compression device of claim 25 , wherein the bottom plug is reversibly mounted in the bottom of the compression tube.
47. The compression device of claim 25 , wherein the bottom plug comprises a mesh disk filter.
48. The compression device of claim 25 , wherein the compression device is a pathologic staging compression device.
49. The compression device of claim 25 , further comprising an automated control system that directs a compression process by actuating and controlling an output of the compression mechanism and monitoring a compression force to perform compression under predetermined conditions.
50. A compression device comprising:
a frame;
a compression tube mounted and held in the frame, the compression tube comprising a cylindrical side wall and defining a cylindrical space between a top open end and a bottom open end for receiving a sample, the cylindrical side wall having a plurality of through-holes;
a bottom plug received in the bottom of the compression tube;
a compression mechanism to compress the sample in the cylindrical space of the compression tube; and
an automated control system that directs a compression process by actuating and controlling an output of the compression mechanism and monitoring a compression force to perform compression under predetermined conditions.
51. The compression device of claim 50 , wherein the automated control system comprises a motor powering a force generator selected from the group consisting of: an electric hydraulic pump, a pneumatic pump, a hydraulic pump, and a worm-gear driven screw jack.
52. The compression device of claim 50 , wherein the automated control system further comprises a controller programmed to limit a maximum current delivered to the motor to a level that corresponds to a maximum force.
53. The compression device of claim 50 , wherein the automated control system comprises at least one sensor that that senses at least one parameter of a sample.
54. The compression device of claim 53 , wherein the sensor is selected from the group consisting of a position sensor, a force sensor, and both a position sensor and a force sensor.
55. The compression device of claim 50 , wherein the compression device is a pathologic staging compression device.
56. A pathologic staging compression kit comprising:
a compression tube comprising a cylindrical side wall and defining a cylindrical space between a top open end and a bottom open end, the cylindrical side wall having a plurality of through-holes;
a bottom plug mounted into the bottom open end of the compression tube;
a cylindrical shield that is shaped to be placed around the compression tube;
a mesh sleeve that fits into the compression tube and holds a sample; and
at least one plunger to compress the sample in the compression tube.
57. A pathologic staging compression kit comprising:
a compression tube comprising a cylindrical side wall and defining a cylindrical space between a top open end and a bottom open end;
a mesh disk filter mounted into the bottom open end of the compression tube; and
at least one plunger to compress the sample in the compression tube.
58. The pathologic staging compression kit of claim 57 , wherein the cylindrical side wall is a solid cylindrical side wall.
59. The pathologic staging compression kit of claim 57 , further comprising a cylindrical shield that is shaped to be placed around the compression tube; wherein the cylindrical side wall has a plurality of through-holes.
60. A method of preparing a tissue sample for pathologic staging using a pathologic staging compression device comprising a compression tube comprising a cylindrical side wall and defining a cylindrical space between a top open end and a bottom open end, the cylindrical side wall having a plurality of through-holes, a bottom plug mounted in the bottom open end of the compression tube, and a cylindrical shield located around the compression tube, comprising the steps of:
soaking the tissue sample in acetone;
compressing the sample in the compression tube of the pathologic staging compression device; and
containing fat removed from the sample during compression with the cylindrical shield.
61. The method of claim 60 , wherein the pathologic staging compression device further comprises a frame; a hydraulic ram held by the frame in alignment with the compression tube; a hydraulic pump providing pressurized hydraulic fluid to the hydraulic ram; a pressure sensor measuring a hydraulic pressure of the pressurized hydraulic fluid; and a bottom plug received in the bottom open end of the compression tube, wherein the compressing step comprises the substeps of:
aligning the hydraulic ram with an opening in a top of the compression tube; and
actuating the hydraulic ram to drive the hydraulic ram into the cylindrical space and compress the sample in the cylindrical space between the hydraulic ram and the bottom plug.
62. The method of claim 61 , wherein the pathologic compression staging device further comprises a stop block below the bottom plug, and the compressing step further comprises the substep of ejecting the sample from the device by removing the stop block from below the bottom plug and actuating the hydraulic ram in a direction of actuation until the bottom plug is driven out of the compression tube.
63. The method of claim 61 , wherein the pathologic staging compression device further comprises a mounting plate connected to the cylindrical shield and a drainage tube extending from a hole in the mounting plate, wherein the containing step further comprises the substep of draining the fat through the drainage tube.
64. The method of claim 61 , wherein the pathologic staging compression device further comprises a drainage planum, wherein the bottom plug is permanently affixed to the drainage planum and the bottom plug is removable from the bottom of the compression tube.
65. The method of claim 64 , further comprising the step of collecting the sample from the compression tube.
66. The method of claim 64 , wherein the pathologic staging compression device further comprises a mesh sleeve that fits into the compression tube and holds the sample.
67. The method of claim 60 , wherein the bottom plug comprises a mesh disk sleeve.
68. The method of claim 60 , wherein the compression step comprises the substep of hand compressing the sample using a hand plunger.
69. The method of claim 60 , wherein the compressing step is directed by an automated control system that actuates and controls an output of a force actuator and monitors a compression force.
Priority Applications (1)
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US15/572,564 US20180156698A1 (en) | 2015-05-12 | 2016-05-11 | Pathologic staging compression apparatus and methods |
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CN109556960B (en) * | 2018-12-17 | 2021-03-12 | 东北大学 | Hydraulic pressure-stabilizing similar material pressing device and using method thereof |
CN109387414B (en) * | 2018-12-19 | 2020-03-24 | 东北大学 | Device and method capable of preparing artificial samples of hydraulic fracturing experiments of various sizes |
IT201900005164A1 (en) * | 2019-04-05 | 2020-10-05 | Micoperi Blue Growth S R L | Microalgae press and microalgae pressing process |
JP2022020075A (en) * | 2020-06-25 | 2022-02-01 | 帝人株式会社 | Biological particle concentrating device |
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Also Published As
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US10126215B2 (en) | 2018-11-13 |
US10775280B2 (en) | 2020-09-15 |
US20170059455A1 (en) | 2017-03-02 |
EP3294069A1 (en) | 2018-03-21 |
EP3294069B1 (en) | 2024-04-24 |
WO2016183135A1 (en) | 2016-11-17 |
US20190033178A1 (en) | 2019-01-31 |
EP3294069A4 (en) | 2019-01-30 |
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