AN APPARATUS FOR COUNTING LIQUID SCINTILLATION SAMPLES

Abstract: The present invention shows a new apparatus in the field of liquid scintillation counting. The conventional liquid scintillation counters have been designed to measure samples in vials, which volume is typically 6 or 20 milliliters. In addition a special purpose liquid scintillation counter, the Betaplate is adapted to measure 6 samples at a time deposited on a multi-well sample plate with fixed format and sample well volume. For avoiding the limitations of the above-mentioned liquid scintillation counters, when samples are deposited on various type multi-well sample plates, a new apparatus is shown which is adapted to measure simultaneously one or several liquid scintillation or corresponding samples deposited in sample plates (10, 20) with various sample well volumes belonging to a preselected assortment of different multi-well sample plate types, each having a characteristic two dimensional array of sample wells.

Description: AN APPARATUS FOR COUNTING LIQUID SCINTILLATION SAMPLES BACKGROUND OF THE INVENTION Liquid scintillation counters are commonly used to measure the count rate or activity of samples containing low energy beta particles or corresponding particles emitting radionuclides such as tritium and carbon-14. The range of the low energy beta particles in the sample is generally few tens of micrometers at the most. As a consequence, the sample to be measured has to be placed in direct contact with a scintillation medium by dissolving or suspending the sample within the liquid scintillation medium in a container so that the emitted beta particles can interact with the molecules of the liquid scintillation medium, which comprises a solvent or solvents and a solute or solutes present in a few percent by weight of the solution. In this interaction process the most of the kinetic energy of the interacted beta particle is absorbed by the solvent and then transferred to the solute which emits scintillation photons, whose amount is proportional to the energy of the interacted beta particle. These scintillation photons are detected by two, in coincidence operating, photomultiplier tubes producing electric pulses. The sum pulse height is proportional to the energy of the interacted beta particle. The conventional liquid scintillation counters have been designed to measure samples which are in sample vials with the scintillation medium. The volume of the sample vial is typically 6 or 20 milliliters. The sample vials are placed into elongated sample holders, which have a plurality of compartments for individual sample vials. A plurality of types of sample vial holders may include, which holders are characterized by the size of the sample vials they are adapted to contain. The sample vial holders are placed on the conveyor of the automatic sample changer system of the liquid scintillation counter. Because the conventional liquid scintillation counters have been designed to measure samples in vials, whose volumes are up to 20 milliliters, difficulties will be encountered, when the sample volumes are only few hundred microliters or less. Typically, this kind of samples with medical or biological interest are prepared in small tubes, which have been inserted into normal vials. In addition, the handling of separate sample vials is very much time consuming and includes a potential risk of setting the sample vials in incorrect order into the sample holders. The sample changing mechanism of such an instrument is also rather complicated, because the vial must be removed from the sample plate holder and must be positioned into a light tight radiation detection chamber, and after counting it must be returned back into the sample holder. In addition to the above mentioned conventional liquid scintillation counters one special purpose liquid scintillation counter exists, namely 1205 Betaplate, which is manufactured by Wallac Oy, Finland. Originally this instrument was designed to measure liquid scintillation samples deposited on a filter mat, which is sealed into a plastic bag with a small amount of scintillation liquid. The maximum diameter of these sample spots is 10 millimeters and the distance between the center points is 15 millimeter. The 96 sample spots are arranged in 6 * 16 matrix format. The Betaplate is provided with 6 detectors, one for each row, thus 6 samples will always be measured simultaneously. Later the Betaplate has been developed to measure samples deposited in a type of multi-well sample plate comprising 96 separate sample wells arranged in the same 6 * 16 format and with same 15 millimeter distance between the center points like in the filter mats. The maximum height of this multi-well sample plate is 7.5 millimeters and the maximum volume of the sample well is limited to 400 microliters. Thus the Betaplate is applicable for measuring 6 samples simultaneously deposited on filter mats or multi-well sample plates having only one format. Unfortunately, in practice there is however a need for multi-well sample plates with various formats and well volumes. In addition, a six detector liquid scintillation counter will be too expensive in some applications due to a relative small amount of samples. SUMMARY OF THE INVENTION The present invention will show a new apparatus adapted to measure simultaneously one or several liquid scintillation or corresponding samples in sample plates with various heights, which sample plates belong to a preselected assortment of different multi-well sample plate types, each having a characteristic two dimensional array of sample wells or vials. One group of multi-well sample plates belonging to the preselected assortment consists of 96-well sample plates having eight rows of wells arranged in twelve columns with 9 millimeters distance between the center points of the wells. The typical volumes of the sample wells of such 96-well sample plates are 200 - 400 microliters depending on the height of the plate. Another group of suitable multi-well sample plates consists of 24-well sample plates having four rows of wells arranged in six columns with 18 millimeters distance between the center points of the wells. Depending on the height of plates, the volume of the wells of such a 24-well sample plates are for example 1 - 5 milliliters. Thus the apparatus according the present invention has been designed to measure liquid scintillation samples, the volume of which are from few microliters up to several milliliters. The apparatus according to the present invention comprises a random access storage compartment for sample plate holders including a plurality of types, each adapted for carrying multi-well sample plates of different types belonging to the preselected assortment. The random access storage compartment may contain any combination of different sample plate holder types where sample holders include all variations from one sample to a full load. The apparatus according to the present invention is provided with a transportation means for taking sample plate holders including a plurality of types characterized by the type of the sample plate , one at a time, from the random access sample plate holder storage compartment to a measuring station provided with 1, 2, 3 or 6 detectors and returning a sample plate holder after measurement back to the storage compartment. The detectors consisting of a pair of in coincidence operating, vertically disposed, photomultiplier tubes are mounted in two detector assemblies, the upper detector assembly is adapted to move in vertical direction in order to enable various heights of the multi-well sample plates. Both detector assemblies are provided with aperture plates having various circular apertures for different well diameters of various type multi-well sample plates. The detector places are arranged in 2 rows with 3 columns having 36 millimeters spacing between the center points. When the apparatus is provided with one detector, it is disposed on the first column of the first row. When the apparatus is provided with 2 detectors, they are disposed on the first columns of the first and the second row. If the apparatus is provided with 3 detectors, they all are placed on the first row. This enables for example the following matrix format and well separation of multi-well sample plates, when the apparatus comprises 1, 2, 3 or 6 detectors : In general, if the distance between the center points of the detector places is d, then the allowed distances of the center points of the sample wells should be d/n, where n ~~ . - f f • • • • The sample plate transportation system of the apparatus according to the present invention is suited for general use in analytical instrumentation, wherein it is required to transport multi-well sample plates provided with different heights and different two dimensional array of sample wells from a random access storage compartment to an analytical measuring station, and then returning to the storage compartment. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 shows a top view of a multi-well sample plate having 96 sample wells in 8 * 12 matrix format. Fig. 2 shows a cross-sectional view of a multi-well sample plate having 96 sample wells in 8 * 12 format taking along line A - A in Fig. 1. Fig. 3 shows a top view of a multi-well sample plate having 24 sample wells in 4 * 6 matrix format. Fig. 4 shows a cross-sectional view of a multi-well sample plate having 24 sample wells in 4 * 6 format taking along line B - B in Fig. 3. Fig. 5 shows a top view of a sample plate holder for 96- well sample plates. Fig. 6 shows a cross-sectional view of a sample plate holder for 96-well sample plates taking along line C - C in Fig. 5. Fig. 7 shows a top view of a sample plate holder for 24- well sample plates. Fig. 8 shows a cross-sectional view of a sample plate holder for 24-well sample plates taking along line D - D in Fig. 5. Fig. 9 is a schematic perspective view of the apparatus showing the arrangement of the relationships between the modules of the apparatus. Fig. 10 is a perspective view of the sample plate holder storage compartment of the apparatus. Fig. 11 is a top view of the x-y-transportation means of the apparatus showing the transportation block in the storage compartment position. Fig. 12 is a top view of the x-y-transportation means of the apparatus showing the transportation block in a position for changing the aperture holes for 24- well plates to the aperture holes for 96-well plates. Fig. 13 is a top view of the x-y-transportation means of the apparatus showing the transportation block in a position for changing the aperture holes for 96- well plates to the aperture holes for 24-well plates. Fig. 14 is a top view of the x-y-transportation means of the apparatus showing a 96-well sample plate in the first measuring position. Fig. 15 is a side view of the measuring station of the apparatus showing the upper detector assembly in the upper position. Fig. 16 is a side view of the measuring station of the apparatus showing the upper detector assembly in the measuring position. DETAILED DESCRIPTION In FIG. 1 there is shown a top view of one of the multi-well sample plates 10 comprising 96-wells 11 in 8 * 12 matrix format produced by a vacuum thermoforming process from transparent material, for example polyethylene terephthalate or other thermoformable plastic. The separations of the wells are 9 millimeters and the maximum diameter of the wells is 7.8 millimeters. The plate is provided with printed lines 12 to prevent the travelling of the light between the wells along the material of the sample plate. The plate is provided with lettering 13 for row identification and numbering 14 for column identification. The corner of the sample plate, which is closest to the well Al (= row A, column 1), is provided with a cut-off beveled edge to force the user to place the sample plate on correct position to the sample plate holder shown in FIG.5. FIG. 2. shows a side view of the 96-well sample plate taking along line A - A in FIG.l. The bottoms of the wells 16 are rounded. The shape of the bottoms can be flat or any other shape as well. The depth of the wells is smaller than the height of the side wall 17 of the plate. The plate can be sealed by an adhesive tape 18 or by a heat sealer apparatus well known in the art. In FIG. 3 there is shown a top view of one of the multi-well sample plates 20 provided with 24 wells 21 in 4 * 6 matrix format produced by a vacuum thermoforming process from transparent material, for example polyethylene terephthalate or other thermoformable plastic. The separations of the wells are 18 millimeters and the maximum diameter of the wells is 13.2 millimeters. The plate is provided with printed lines 22 to prevent the travelling of the light between the wells 21 along the material of the sample plate. The plate is provided with lettering 23 for row identification and numbering 24 for column identification. The corner of the sample plate, which is closest the well Al (= row A, column 1), is provided with a cut-off beveled edge to force the user to place the sample plate on correct position to the sample plate holder shown in FIG.7. FIG. 4. shows a side view of the 24-well sample plate taking along line B - B in FIG.3. The bottoms of the wells 26 are flat. As well the shape of the bottoms can be rounded or any other shape. The depth of the wells is smaller than the height of the side wall 27 of the plate. The plate can be sealed by an adhesive tape 18 or by a heat sealer apparatus well known in the art. FIG. 5 shows a sample plate holder 30a suitable for 96-well sample plates 10 shown in FIG. 1 and 2 and produced by an injection molding process from a light-impermeable material with high degree of reflectivity for scintillation light, for example a special-grade polycarbonate plastic containing high amount of white pigment. FIG. 6 shows a side view of 96-well sample plate holder 30a taking along line C-C in FIG. 5 with a 96-well sample plate 10. The sample plate holder 30a is provided with circular through holes 31a for the wells 11 of the sample plate 10. The sample plate holder is provided with a cut-off or bevel corner 32 to engage the sample plate in a single position. The right side 33 of the sample plate holder 30 is provided with a slot 34 and the left side 35 of the sample plate holder 30a is provided with another slot 36a. The purpose of these slots 34 and 36a will be explained later. The rear side 37 of the sample plate holder 10 is provided with two identical pivot holes 38 from its top to its bottom with open slits 39. The x-y-transportation system comprises a transportation block provided with two vertical positioned pivots, which fit to said pivot holes of the sample plate holders. The front side 40 of the sample plate holder 10 is provided with means 41 for carrying a detachable support plate 42, on which support plate can be attached at least one bar code label. FIG. 7 shows a sample plate holder 30b suitable for 24-well sample plates 20 shown in FIG. 3 and 4 and the like produced by an injection molding process from a light-impermeable material with high degree of reflectivity for scintillation light, for example a special-grade polycarbonate plastic containing high amount of white pigment. The sample plate holder 30b is provided with circular through holes 31b for the wells 21 of the sample plate 20. The sample plate holder is provided with a cut-off or bevel corner 32 to engage the sample plate in a single position. The right side 33 of the sample plate holder 30 is provided with a slot 34 and the left side 35 of the sample plate holder 30b is provided with another slot 36b. The purpose of these slots 34 and 36b will be explained later. The rear side 37 of the sample plate holder 10 is provided with two identical pivot holes 38 from its top to its bottom with open slits 39. The x-y-transportation system comprises a transportation block provided with two vertical positioned pivots, which fit to said pivot holes of the sample plate holders. The front side 40 of the sample plate holder 10 is provided with means 41 for carrying a detachable support plate 42, on which support plate can be attached at least one bar code label. The outer portions of the sample plate holder 30a for 96- well sample plates 10 and the sample plate holder 30b for 24-well sample plates 20 are identical except the distance of slots 36a and 36b from the rear surfaces 37 marked "X" and "Y", respectively. The control means of the apparatus will use this difference in order to distinguish these two sample plate holders for two kind multi-well sample plates having different two dimensional array of sample wells. FIG. 8 shows a side view of 24-well sample plate holder 30b taking along line D-D in FIG. 7 with a 24-well sample plate 20. In FIG. 9 there is shown a schematic perspective arrangement of the relationships between the sample plate holder storage module 200, the horizontal plane 301 of the x-y-transportation unit 300, the upper detector assembly 410 and the lower detector assembly 420. The housing 110 comprising a door 111 of the apparatus is drawn schematically by dashed lines. The storage module 200 for different type sample plate holders shown in FIG. 10 is comprising a case 201 and a vertically moving storage compartment 202 provided with U-shaped guide members 203, attached on the both inner sides of the moving storage compartment 202, for sample plate holders like 30a or 30b. If the total height of the sample plate holder is less than the separation of the guide members 15 millimeters, then 20 sample plate holders can be placed in the storage compartment 202. If the height is between 15 and 30 millimeters, then 10 sample plate holders can be placed in the storage compartment 202. If the height is between 30 and 45 millimeters, then 7 sample plate holders can be placed in the storage compartment. The U-shape of the guide members 203 hinder the movement of the sample plate holders in the vertical direction. It should be noted that the operation may be carried out with any number of sample plate holders from one to a full load and any combination of sample plate holders types are allowed. The control means of the apparatus is adapted to stop the storage compartment 202 in such positions that the x-y-transportation means 300 is enabled to transport the each sample plate holders ,one at a time, to the counting station formed by the upper and the lower detector assembly 410 and 420 respectively and back to the storage compartment 202. This enables an entirely free order to measure the sample plates deposited on the sample plate holders in the storage compartment 202. Two plastic blocks 204a and 204b are attached to the both outer sides of said vertically moving storage compartment 202. Said blocks 204a and 204b have circular openings 205 which fit vertical guide rods 206 attached to the case 201 of the storage module 200 permitting said plastic blocks 204a and 204b, and thus the attached storage compartment 202, to travel vertically along said guide rods 206. To provide the vertical motion, the lower plastic blocks 204a on the both side of said storage compartment 202 have attached to cogged belts 206. Said belts 206 extend around the drive cogged wheels 207 and the idler cogged wheels 208. Both drive cogged wheels 207 are attached with an axle 209 to a cogged wheel 210 which is operated using a cogged belt 211 extended around drive cogged wheel 212 attached to the shaft 213 of the stepper motor 214 which is attached to the case 201 of said storage compartment module 200. When the motor 214 rotates with the drive wheels 207 to first direction, the storage compartment 202 is activated to travel upwards along the vertical rods 206. When the motor 214 operates in the opposite direction, the storage compartment 202 is activated to move downwards. FIG. 11 shows that, when a sample plate holder 30b is placed in the storage compartment 202, an angular part of a spring tab 216, attached with each guide member 203 on the right side of the storage compartment 202 , is engaged with the slot 34 in the right side 33 of the sample plate holder 30a or 30b securing correct position of the sample plate holder to the guide members 203. The storage compartment 202 is provided with first control means, which is controlling the vertical positioning of the storage compartment 202, comprising an electro-optical sensor 217 and a plate 219 with separate tabs 220 corresponding each guide members 203 on the right side of the storage compartment 202. The tab plate 219 is attached to the sample plate holder compartment 202 by two screws 221 through adjustment permitting elongated openings 222. The electro-optical sensor 217 is mounted to the horizontal plane 301 of x-y-transportation module 300 by a vertically adjustable member 302, which permits the vertical adjustment of the position of the sensor. The widths of the tabs 221 are equal except more narrow one 223, which corresponds to the lowest sample plate position in the storage compartment 202. The vertical position of the electro-optical sensor 217 and the tab plate 219 is adjusted so that the upper edge of a tab interrupts the light path of the sensor, when the lower surface of a sample plate holder 30a or 30b is in the same level than the upper surface of the horizontal plane 301 of the x-y-transportation module 300. In the case of uncontrolled situation the storage compartment 202 is forced by the control system of the apparatus to move upwards until the electro-optical sensor 217 detects the upper edge of the narrow tab 223. This occurrence informs that the lowest sample plate holder position of the storage compartment 202 is at the same level as the horizontal plane 301 x-y-transportation module 300. The storage compartment 202 is provided with second control means to detect the type of the sample plate holder and vacant positions of the storage compartment 202 comprising an electro-optical sensor 224 attached on the case 201 of the storage compartment module 200 and spring tabs 225 attached on each guide members 203 on the left side of the storage compartment 202. When the sample plate holder 30 a or 30 b is in the correct position in the storage compartment 202, the left side 35 of the sample plate holder pushes an angular part of spring tab 225 so that the edge 226 of said tab 225 interrupts the light path of the electro-optical sensor 224, when the corresponding sample plate holder position of the storage compartment 202 is in the same level than the horizontal plane 301 of the x-y-transportation module 300 indicating that the position is occupied. At the same this spring tab 225 forces the sample plate holder to abut the right side of the storage compartment 202 securing the correct positioning of the sample plate holders in the lateral direction. The detecting of the sample plate holder type is described later. In the normal mode of operation the storage compartment 202 is stopped by the control system of the apparatus, when a lower surface of a sample plate holder, which is in a sample plate holder position formed by guide members 203, is exactly at same level than the upper surface of the horizontal plane 301 of the x-y-transportation module 300, permitting the x-y-transportation means to move that sample holder to the counting station consisting upper 410 and lower 420 detector assemblies and to return it back to same position in storage compartment 202. For the connecting of the sample plate holder to the x-y-transportation means, the sample plate holders 30a and 30b are provided with two pivot holes 38 from its top to its bottom with open slits 39 at the rear 37 of the sample plate holder. The x-y-transportation means comprise a transportation block 303 provided with two vertical positioned pivots 304, which fit to said pivot holes 38 of the sample plate holders 30a, 30b. The height of these pivots 304 are smaller than the space between two nearest sample plate holders 30a, 30b in the storage compartment 202. The pivots 304 are attached to the front of the transportation block with rods 305, which fit to said slits 39 of the sample plate holders 30a, 30b. The space between said pivots 304 provided with rods 305 is equivalent to the space between said pivot holes 38 provided with slits 39. When the apparatus is idle or when the sample plate holder compartment is moving, the transportation block 303 is situated so that the pivots 305 attached to it are concentric with the pivot holes 38 of the sample plate holder 30a, 30b. If the apparatus is idle the storage compartment 202 is stopped in such position that said pivots 305 are situated between two sample plate holder positions enabling loading and unloading of each sample plate holder position. When connection takes place with a sample plate holder, the storage compartment 202 is stopped at the same level as the horizontal plane 301 of the x-y-transportation module. In this position the pivots 304 attached to the transportation block 304 with rods 305 are engaged with the pivot holes 38 of that sample plate holder. To secure more rigid connection the transportation block 303 is provided with spring tab 323, which pushes the rear side of the sample plate holder. The x-y-transportation module comprises a horizontal aluminum plate 301 and a transportation means, attached to the plate 301. The plate is provided with two perpendicular guide rods 306, 307 for said transportation means. One guide rod 306 is parallel to the X-axis and another is parallel to Y-axis 307. Both ends of the rods 306 and 307 are mounted to vertical members 308 attached to the plate 301. The X-guide rod 306 is provided with X-cursor block 309, which can ride along the X-guide rod 306, and Y-guide rod 307 is provided with Y-cursor block 310, which can ride along the Y-guide rod 307. X-cursor block 309 is provided with a rod 311, which is parallel to the Y-axis. Y-cursor block 310 is provided with a rod 312, which is parallel to the X-axis. The vertical position of these rods 311, 312 attached to the cursor blocks 309, 310 from the plate surface 301 differs so that the rods 311, 312 can cross each other. The transportation block 303 is provided with a transverse channel 313 which fits to the rod 311 attached to X-cursor block 303 so that the transportation block 303 can travel in the Y-direction along this rod 311. Two plastic blocks 314a and 314b are attached to the upper surface of the transportation block 303. These two blocks 314a and 314b are provided with channels 315a and 315b which fit to the rod 312 attached to Y-cursor block 307 so that the transportation block 303 can travel in the X-direction along said rod 312. Thus the transportation block 303 is moving in the horizontal plane 301 of the x-y-transportation module 300 with the cursor blocks 309 and 310. The position of the transportation block 303 relative to the zero-position at the horizontal plane 301 corresponds to the vector sum of the positions of the cursor blocks 309 and 310. The X- and Y-cursor blocks 309, 310 are driven independently of each other along the X- and Y-rods 306, 307 by two stepper motors deposited beneath of the horizontal plate 301 (not shown) . The Y-cursor block 310 is attached to the cogged belt 316, which extends around the drive cogged wheel 317 and the idle cogged wheel 318. The drive cogged wheel 317 is attached directly to the shaft of the stepped motor. The X-cursor block 309 is driven in similar way, the driving system (not shown) is deposited beneath of the plate 301. The zero position of the X-cursor block 309 is controlled by an electro-optical sensor 319. The X-cursor block 309 is provided with a tab 321, which interrupts the light path of said sensor 319, when that cursor 309 comes to the zero position. The zero position of the Y-cursor 310 block is controlled by another electro-optical sensor 320. The Y-cursor block 310 is provided with a tab 321, which interrupts the light path of said sensor 320, when that cursor 310 comes to the zero position. In addition the position of the sample plate storage compartment 202 of the Y-cursor block 310 is controlled by an electro-optical sensor 322, which light path is interrupted when Y-cursor block 310 comes to the sample plate holder compartment 202 position, where the pivots 304 of the transportation block 303 are concentric with the pivot holes 38 of the sample plate holders, which are in the storage compartment 202. The upper and lower detector assemblies 410 and 420 are provided aperture plates 411 and 421 ,respectively, disposed in the front of photomultiplier tubes 430 of the detector assemblies. The aperture plate 411 of the upper detector assembly 410 is not shown, but it is exactly a mirror image of the aperture plate 421 of the lower detector assembly 420. The aperture plates are provided with circular aperture holes 422 and 423 adapted to the diameters of the wells in the 96-well or 24-well sample plates, respectively. When the x-y-transportation means takes the sample plate holder from the storage compartment 202 by the means of the transportation block 303, the control system of the apparatus first checks if the sample plate holder is adapted to 96- or 24-well sample plates. The checking happens so that the transportation block 303 with the sample plate holder moves in the direction of the Y-axis until the slot 36a of the sample plate holder 30a for 96- well sample plate or the slot 36b of the sample plate holder 30b for 24-well sample plate engage with the angular part of the spring tab 225. Then this happens the edge 226 of the spring tab 225 finish interrupting the light path of the electro-optical sensor 224. Because the distances X and Y of slots 36a and 36b from the rear surface of the sample plate holders 30a or 30b are different, the control system detects the type of the sample plate holder. If the positions of the aperture plates 411 and 421 do not correspond the type of the sample plate holder , the x-y-transportation means returns the sample plate holder to the storage compartment 202 and changes the positions of the aperture plates 411 and 421 to correspond to the sample plate holder type. This happens so that the control system of the apparatus moves the transportation block 303 to such position that the spring loaded pin 324 is concentric with the pin holes 424 of the ledges 425 of the aperture plates 421 and 411 (FIG. 12 a). Next the upper detector assembly 420 moves downwards until the spring loaded pin 324 of the transportation block 303 engages with the pin holes 424 of the both aperture plates 411 and 421. After this the control system of the apparatus moves the transportation block 303 with attached aperture plates to a new position shown in FIG. 13 so that the aperture holes 422 or 423 corresponds to the well diameters of the sample plate. In this example the first position of the aperture plates 421 was such that the aperture holes 423 for the 24-well sample plates were concentric with the photocathodes of the photomultiplier tubes 430 of the upper and lower detector assembly 410, 420 and the second position of the aperture plates 421 shown in FIG. 13 was such that the aperture holes 422 for the 96-well sample plates were concentric with the photocathodes of the photomultiplier tubes 430. It should be understand that this operation should happen as well in the opposite direction from position shown in FIG. 13 to position shown in 12. When the control system of the apparatus has secured that the positions of the aperture plates 411 and 421 correspond to the type of the next sample plate holder 30a or 30b, the transportation means moves the sample plate holder 30a or 30b carrying the sample plate 10 or 20 by the means of the transportation block 303 past an electro-optical reader 325, which reads the bar code labels attached on the ID support plate 42 of the sample plate holder 30a or 30 b. The bar code labels convey information to the control system of the apparatus for controlling the operation of the apparatus, for example, which measuring parameters should be used. After this the apparatus moves the sample plate holder 30a or 30b carrying the sample plate 10 or 20 to the measuring station formed by the upper and lower detector assemblies 410 and 420 shown in FIGS. 15 and 16. The apparatus of the instrument is provided with 1, 2, 3 or 6 detectors consisting of a pair of in coincidence operating photomultiplier tubes mounted in two detector assemblies 410 and 420 shown in FIGS. 9, 15 and 16. The upper detector assembly 410 is adapted to move in the vertical direction in order to enable various heights of the multi-well sample plates. Both detector assemblies 410 and 420 are provided with aperture plates 411 and 421, respectively, having circular apertures 422 and 423 in the front of the photocathodes of the photomultiplier tubes 430 for 96-well sample plates 10 and 24-well sample plates 20. The 6 places of the photomultiplier tubes 430 are arranged in 2 rows with 3 columns having 36 millimeters spacing between the center points as shown for example in FIG. 11 for the lower detector assembly 420. When the apparatus is provided with one detector, the photomultiplier tube 430 of the lower detector assembly 420 is deposited on the first column of the first row (position 441). The photomultiplier tube 430 of the upper detector assembly 420 is deposited on the corresponding place so that these in coincidence operating photomultiplier tubes 430 are concentric. When the apparatus is provided with 2 detectors, the photomultiplier tubes 430 of the lower detector assembly 420 are deposited on the first columns of the first and the second rows (positions 441 and 444). The photomultiplier tubes 430 of the upper detector assembly 410 are deposited on the corresponding places. When the apparatus is provided with 3 detectors, the photomultiplier tubes 430 of the lower detector assembly 420 are deposited on the first row (positions 441, 442 and 443) and the photomultiplier tubes 430 of the upper detector assembly 410 are deposited on the corresponding places. This detector arrangement enables the matrix format and well separation of 96-well sample plate 10 and 24-well sample plate 20 and corresponding sample plates, when the apparatus is provided 1, 2, 3 or 6 detectors. Naturally a sample plate having 6 sample wells with 36 millimeters separation is allowed. In general, if the distance of the center points of the detector positions is d, then the allowed distances of the center points of the sample wells of the sample plates should be d/n, where In FIG. 14 there is a 96-well sample plate 10 carried by the corresponding sample plate holder 30a stopped in the first measuring position. In this position the first, the fifth and the ninth sample wells of the first and the fifth rows of the sample plate 10 are measured, if the apparatus is provided with six detectors. ( If the sample plate is 24-well 20, when the first, the third and the fifth sample wells of the first and the third rows are measured. ) When the apparatus has measured these sample wells, the transportation means moves the sample plate holder 30a or 30b carrying the sample plate 10 or 20 to the second measuring position and so on until the whole sample plate is measured. After it the sample plate with the sample plate holder is moved back to the storage compartment 202 and the next sample plate holder, whose position is defined by the control means of the apparatus according to the selection of the user, is moved past the ID reader 325 to the counting station. In FIGS. 15 and 16 are shown the movement of the upper detector assembly 410. When the transportation block is moving the upper detector assembly is in the up position shown in FIG. 15. When the sample plate holder 30a or 30b with sample plates 10 or 20 is in the measuring position the upper detector assembly moves downwards until it touches the sample plate 10 or 20 carried by the sample plate holder 30a or 30b. The upper detector assembly 410 is adapted to stop in any position enabling the different heights of the sample plate holders. The upper detector assembly is mounted on a support block 450 which can travel along two vertical rods (not shown) attached on the base support member 451. The support block 450 hangs on a travel member 452 by threaded coupling so that it is mounted on a elongated threaded lead screw 453 driven by a stepper motor (not shown) . The support block 450 is provided with an electro-optical sensor 454 and the travel member 452 with a tab plate 455, which interrupts the light path of the electro-optical sensor 454, when the support block 450 hangs on the travel member 452. If the upper detector assembly 410 is disabled to move with the travel member 452, the travel member 452 with the tab plate 455 continues its motion downwards until its separates so much from the support block 450 that the tab plate 455 finishes the interruption of the light path of the electro-optical sensor 454. The apparatus according to the present invention is not confined to the above embodiments alone, but it may show even considerable variation within the scope of the patent claims.

Claims: CLAIMS 1. Apparatus for counting liquid scintillation samples, characterized in that said apparatus is adapted to count simultaneously one or several samples in sample plates (10, 20), said sample plates belonging to a preselected assortment of different multi-well sample plate types, each type having a characteristic two dimensional array of sample wells or vials. 2. Apparatus according to claim 1, characterized in that said apparatus is provided with a transportation system adapted for transporting said different multi-well sample plates (10, 20) belonging to said preselected assortment. 3. Apparatus according to claim 2, characterized in that the first substantial part of said transportation system comprises sample plate holders (30a, 30b) including a plurality of holder types, each adapted for carrying multi-well sample plates (10, 20) belonging to said preselected assortment. 4. Apparatus according to claim 3, characterized in that said sample plate holders (30a, 30b) are provided with registration means for distinguishing the different types of sample plate holders. 5. Apparatus according to claim 3, characterized in that said different types of sample plate holders (30a, 30b) are provided with an equivalent coupling means for said transportation means. 6. Apparatus according to claim 3, characterized in that said different types of sample plate holders (30a, 30b) are provided with equivalent sample plate identification means having a detachable support plate (42) associated with each of said sample plate holders, on which support plate at least one bar code label can be attached. 7. Apparatus according to claim 3, characterized in that the second substantial part of said transportation system is a random access sample plate holder storage compartment (202), which has at least one position for said sample plate holders (30a, 30b). 8. Apparatus according to claim 7, characterized in that said sample plate holder storage compartment (202) is enabled to move in the vertical direction. 9. Apparatus according to claim 8, characterized in that said sample plate holder storage compartment (202) is driven by a stepper motor (214) and controlled by electro-optical sensors (217, 214). 10. Apparatus according to claim 9, characterized in that the third substantial part of said transportation system is a horizontal plane (301) provided with a transportation means including a transportation block (303) adapted to move said sample plate holders (30a, 30b) in said horizontal plane, which horizontal plane is associated with said sample plate holder storage compartment (202) and said transportation block is provided with a coupling means for said sample plate holders. 11. Apparatus according to claim 10, characterized in that said horizontal plane (301) with the transportation means is provided with an electro-optical reader (325) for said bar code labels attached on detachable support plates (42) associated with said sample plate holders (30a, 30b). 12. Apparatus according to claim 10, characterized in that said horizontal plane (301) with the transportation means is provided with two stepper motors for driving said transportation means and two electro-optical sensors (319, 320) for controlling zero position of said transportation means and one electro-optical sensor (322) for controlling the coupling position of said sample plate holders (30a, 30b) in said storage compartment (202). 13. Apparatus according to claim 1, characterized in that an essential part of said apparatus is a counting station comprising one or several detectors, each provided with two vertically positioned photomultiplier tubes (430), mounted in two detector assemblies (410, 420), where at least the upper assembly is adapted to move in vertical direction. 14. Apparatus according to claim 13, characterized in that said detector assemblies are provided with aperture means comprising a plurality of apertures (422, 423) for different well diameters of said multi-well sample plates (10, 20). 15. Apparatus according to claim 14, characterized in that said apertures are switched by said horizontal plane moving transportation block (303) to correspond different well diameters of said multi-well sample plates (10, 20). 16. Apparatus according to claim 15, characterized in that said transportation means associated with said sample plate holder storage compartment (202) takes one sample plate holder (30a, 30b) at a time and transports it to said counting station and moves said sample plate holder in proportion to said counting station in order to enable to count each sample well of said different types of multi-well sample plates (10, 20).

Inventors: LEHTINEN KAUKO, SONNE VESA, YRJOENEN TAPIO, LEHTINEN, KAUKO, SONNE, VESA, YRJOENEN, TAPIO
Applicants: WALLAC OY
Application year: 1990
Main classification: G01N35
IPC codes: G01N35, G01T1, G01T7