Note: Descriptions are shown in the official language in which they were submitted.
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SYSTEMS AND METHODS FOR ASSAYING AN
ELUATE OF A RADIONUCLIDE GENERATOR
FIELD
[0001] The field of the disclosure relates generally to radionuclide
generators and, more particularly, to systems of methods for assaying an
eluate of
a radionuclide generator.
BACKGROUND
[0002] Molybdenum-99 (Mo-99) is the parent radioisotope used for
generating Technetium-99m (Tc-99m) for diagnostic medical purposes.
Specifically, quantities up to 6000 Curies (Ci) can be used to produce
Technetium
generators. Accordingly, samples from the formulation process must be tested
(i.e., assayed) for Molybdenum-99 content.
[0003] Conventional assaying methods use liquid transfer vials or
containers to elute the Technetium generator, and subsequently transfer the
vial or
container to a radiation detection device to measure or assay the radioactive
content of the eluate. The use of transfer vials or containers has several
drawbacks including additional costs of manufacturing sterile evacuated vials,
and
additional costs and processing associated with disposing of the vial after
the
assay process is complete. Accordingly, a need exists for improved systems and
methods for assaying radionuclide generators.
[0004] This Background section is intended to introduce the reader
to various aspects of art that may be related to various aspects of the
present
disclosure, which are described and/or claimed below. This discussion is
believed
to be helpful in providing the reader with background information to
facilitate a
better understanding of the various aspects of the present disclosure.
Accordingly,
it should be understood that these statements are to be read in this light,
and not
as admissions of prior art.
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BRIEF SUMMARY
[0005] In one aspect, a system for assaying an eluate includes a
radiation detection device, a fluid handling system, and a connection
interface. The
radiation detection device includes a collection reservoir, and is adapted to
measure a radioactive content of a sample within the collection reservoir. The
fluid
handling system includes a fluid supply line, a suction line, and a fluid
discharge
line, each connected to the collection reservoir. The connection interface
connects
a radionuclide generator to the collection reservoir via the fluid handling
system.
The fluid handling system is configured to generate a negative pressure within
the
collection reservoir via the suction line such that an eluate from the
radionuclide
generator is supplied to the collection reservoir via the fluid supply line.
[0006] In another aspect, a method of assaying an eluate includes
connecting a radionuclide generator to a connection interface of a fluid
handling
system. The fluid handling system includes a fluid supply line, a suction
line, and a
fluid discharge line, each connected to a collection reservoir of a radiation
detection device. The method further includes eluting the radionuclide
generator to
produce an eluate, where eluting the radionuclide generator includes
generating a
negative pressure within the collection reservoir via the suction line. The
method
further includes directing the eluate into the collection reservoir via the
fluid supply
line, determining, using a processor, a radioactive content of the eluate, and
discharging the eluate from the collection reservoir via the fluid discharge
line.
[0007] Various refinements exist of the features noted in relation to
the above-mentioned aspects. Further features may also be incorporated in the
above-mentioned aspects as well. These refinements and additional features may
exist individually or in any combination. For instance, various features
discussed
below in relation to any of the illustrated embodiments may be incorporated
into
any of the above-described aspects, alone or in any combination.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a schematic view of a system for producing
radionuclide generators.
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[0009] FIG. 2 is a perspective view of a radionuclide generator.
[0010] FIG. 3 is a schematic view of an example assay system
suitable for use in the system of FIG. 1.
[0011] FIG. 4 is a block diagram of a controller included in the
assay system of FIG. 3.
[0012] FIG. 5 is a top plan view of another embodiment of an
example assay system suitable for use in the system of FIG. 1.
[0013] FIG. 6 is a perspective view of a portion of the assay system
shown in FIG. 5.
[0014] FIG. 7 is a top plan view of a fluid handling subsystem of the
assay system shown in FIG. 5.
[0015] FIG. 8 is a sectional view of a portion of a radiation detection
device included in the assay system of FIG. 5.
[0016] Corresponding reference characters indicate corresponding
parts throughout the several views of the drawings.
DETAILED DESCRIPTION
[0017] Radioactive material is used in nuclear medicine for
diagnostic and therapeutic purposes by injecting a patient with a small dose
of the
radioactive material, which concentrates in certain organs or regions of the
patient.
Radioactive materials typically used for nuclear medicine include Technetium-
99m
("Tc-99m"), Indium-111m ("In-111"), Thallium-201, and Strontium-87m, among
others.
[0018] Such radioactive materials may be produced using a
radionuclide generator. Radionuclide generators generally include a column
that
has media for retaining a long-lived parent radionuclide that spontaneously
decays
into a daughter radionuclide that has a relatively short half-life. The column
may be
incorporated into a column assembly that has a needle-like outlet port that
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receives an evacuated vial to draw saline or other eluant liquid, provided to
a
needle-like inlet port, through a flow path of the column assembly, including
the
column itself. This liquid may elute and deliver daughter radionuclide from
the
column and to the evacuated vial for subsequent use in nuclear medical imaging
applications, among other uses.
[0019] FIG. 1 is a schematic view of a system 100 for
manufacturing radionuclide generators. The system 100 shown in FIG. 1 may be
used to produce various radionuclide generators, including, for example and
without limitation, Technetium generators, Indium generators, and Strontium
generators. The system 100 of FIG. 1 is particularly suited for producing
Technetium generators. A Technetium generator is a pharmaceutical drug and
device used to create sterile injectable solutions containing Tc-99m, an agent
used
in diagnostic imaging with a relatively short 6 hour radiological half-life,
allowing
the Tc-99m to be relatively quickly eliminated from human tissue. Tc-99m is
"generated" via the natural decay of Molybdenum ("Mo-99"), which has a 66 hour
half-life, which is desirable because it gives the generator a relatively long
two
week shelf life. During generator operation (i.e., elution with a saline
solution), Mo-
99 remains chemically bound to a core alumina bed (i.e., a retaining media)
packed within the generator column, while Tc-99m washes free into an elution
vial,
ready for injection into a patient. While the system 100 is described herein
with
reference to Technetium generators, it is understood that the system 100 may
be
used to produce radionuclide generators other than Technetium generators.
[0020] As shown in FIG. 1, the system 100 generally includes a
plurality of stations. In the example embodiment, the system 100 includes a
cask
loading station 102, a formulation station 104, an activation station 106, a
fill/wash
station 108, an assay/autoclave loading station 110, an autoclave station 112,
an
autoclave unloading station 114, a quality control testing station 116, a
shielding
station 118, and a packaging station 120.
[0021] The cask loading station 102 is configured to receive and
handle casks or containers of radioactive material, such as a parent
radionuclide,
and transfer the radioactive material to the formulation station 104.
Radioactive
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material may be transported in secondary containment vessels and flasks that
need to be removed from an outer cask prior to formulation. The cask loading
station 102 includes suitable tooling and mechanisms to extract secondary
containment vessels and flasks from outer casks, as well as transfer of flasks
to
the formulation cell. Suitable devices that may be used in the cask loading
station
102 include, for example and without limitation, telemanipulators.
[0022] At the formulation station 104, the raw radioactive material
(i.e., Mo-99) is quality control tested, chemically treated if necessary, and
then pH
adjusted while diluting the raw radioactive material to a desired final target
concentration. The formulated radioactive material is stored in a suitable
containment vessel (e.g., within the formulation station 104).
[0023] Column assemblies containing a column of retaining media
(e.g., alumina) are activated at the activation station 106 to facilitate
binding of the
formulated radioactive material with the retaining media. In some embodiments,
column assemblies are activated by eluting the column assemblies with a
suitable
volume of HCI at a suitable pH level. Column assemblies are held for a minimum
wait time prior to charging the column assemblies with the parent
radionuclide.
[0024] Following activation, column assemblies are loaded into the
fill/wash station 108 using a suitable transfer mechanism (e.g., transfer
drawer).
Each column assembly is then charged with parent radionuclide by eluting
formulated radioactive solution (e.g., Mo-99) from the formulation station 104
through individual column assemblies using suitable liquid handling systems
(e.g.,
pumps, valves, etc.). The volume of formulated radioactive solution eluted
through
each column assembly is based on the desired Ci activity for the corresponding
column assembly. The volume eluted through each column assembly is equivalent
to the total Ci activity identified at the time of calibration for the column
assembly.
For example, if a volume of formulated Mo-99 required to make a 1.0Ci
generator
(at time of calibration) is 'X', the volume required to make a 19.0Ci
generator is
simply 19 times X. After a minimum wait time, the charged column assemblies
are
eluted with a suitable volume and concentration of acetic acid, followed by an
elution with a suitable volume and concentration of saline to "wash" the
column
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assemblies. Column assemblies are held for a minimum wait time before
performing assays on the column assemblies.
[0025] The charged and washed column assemblies (or
radionuclide generators) are then transferred to the assay/autoclave load
station
110, in which assays are taken from each column assembly to check the amount
of parent and daughter radionuclide produced during elution. Each column
assembly is eluted with a suitable volume of saline, and the resulting
solution is
assayed to check the parent and daughter radionuclide levels in the assay.
Where
the radioactive material is Mo-99, the elutions are assayed for both Tc-99m
and
Mo-99. Column assemblies having a daughter radionuclide (e.g., Tc-99m) assay
falling outside an acceptable range calculation are rejected. Column
assemblies
having a parent radionuclide (e.g., Mo-99) breakthrough exceeding a maximum
acceptable limit are also rejected. As described further herein, systems and
methods of the present disclosure facilitate assaying elutions of radionuclide
generators without the use of transfer vials or other liquid containers that
require
transfer to a radiation detection device. For example, embodiments of the
systems
and methods described herein facilitate eluting a radionuclide generator
directly
into the collection reservoir of a radiation detection device.
[0026] Following the assay process, tip caps are applied to the
outlet port and the fill port of the column assembly. Column assemblies may be
provided with tip caps already applied to the inlet port. If the column
assembly is
not provided with a tip cap pre-applied to the inlet port, a tip cap may be
applied
prior to, subsequent to, or concurrently with tip caps being applied to the
outlet port
and the fill port. Assayed, tip-capped column assemblies are then loaded into
an
autoclave sterilizer located in the autoclave station 112 for terminal
sterilization.
The sealed column assemblies are subjected to an autoclave sterilization
process
within the autoclave station 112 to produce terminally-sterilized column
assemblies.
[0027] Following the autoclave sterilization cycle, column
assemblies are unloaded from the autoclave station 112 into the autoclave
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unloading station 114. Column assemblies are then transferred to the shielding
station 118 for shielding.
[0028] Some of the column assemblies are transferred to the
quality control testing station 116 for quality control. In the example
embodiment,
the quality control testing station 116 includes a QC testing isolator that is
sanitized
prior to QC testing, and maintained at a positive pressure and a Grade A clean
room environment to minimize possible sources of contamination. Column
assemblies are aseptically eluted for in-process QC sampling, and subjected to
sterility testing within the isolator of the quality control testing station
116. Tip caps
are reapplied to the inlet and outlet needles of the column assemblies before
the
column assemblies are transferred back to the autoclave unloading station 114.
[0029] The system 100 includes a suitable transfer mechanism for
transferring column assemblies from the autoclave unloading station 114 (which
is
maintained at a negative pressure differential, Grade B clean room
environment) to
the isolator of the quality control testing station 116. In some embodiments,
column
assemblies subjected to quality control testing may be transferred from the
quality
control testing station 116 back to the autoclave unloading station 114, and
can be
re-sterilized and re-tested, or re-sterilized and packaged for shipment. In
other
embodiments, column assemblies are discarded after being subjected to QC
testing.
[0030] In the shielding station 118, column assemblies from the
autoclave unloading station 114 are visually inspected for container closure
part
presence, and then placed within a radiation shielding container (e.g., a lead
plug).
The radiation shielding container is inserted into an appropriate safe
constructed of
suitable radiation shielding material (e.g., lead, tungsten or depleted
uranium).
Shielded column assemblies are then released from the shielding station 118.
[0031] In the packaging station 120, shielded column assemblies
from the shielding station 118 are placed in buckets pre-labeled with
appropriate
regulatory (e.g., FDA) labels. A label uniquely identifying each generator is
also
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printed and applied to each bucket. A hood is then applied to each bucket. A
handle is then applied to each hood.
[0032] The system 100 may generally include any suitable
transport systems and devices to facilitate transferring column assemblies
between stations. In some embodiments, for example, each of the stations
includes at least one telemanipulator to allow an operator outside the hot
cell
environment (i.e., within the surrounding room or lab) to manipulate and
transfer
column assemblies within the hot cell environment. Moreover, in some
embodiments, the system 100 includes a conveyance system to automatically
transport column assemblies between the stations and/or between substations
within one or more of the stations (e.g., between a fill substation and a wash
substation within the fill/wash station 108).
[0033] In the example embodiment, some stations of the system
100 include and/or are enclosed within a shielded nuclear radiation
containment
chamber, also referred to herein as a "hot cell". Hot cells generally include
an
enclosure constructed of nuclear radiation shielding material designed to
shield the
surrounding environment from nuclear radiation. Suitable shielding materials
from
which hot cells may be constructed include, for example and without
limitation,
lead, depleted uranium, and tungsten. In some embodiments, hot cells are
constructed of steel-clad lead walls forming a cuboid or rectangular prism. In
some
embodiments, a hot cell may include a viewing window constructed of a
transparent shielding material. Suitable materials from which viewing windows
may
be constructed include, for example and without limitation, lead glass. In the
example embodiment, each of the cask loading station 102, the formulation
station
104, the fill/wash station 108, the assay/autoclave loading station 110, the
autoclave station 112, the autoclave unloading station 114, and the shielding
station 118 include and/or are enclosed within a hot cell.
[0034] In some embodiments, one or more of the stations are
maintained at a certain clean room grade (e.g., Grade B or Grade C). In the
example embodiment, pre-autoclave hot cells (i.e., the cask loading station
102,
the formulation station 104, the fill/wash station 108, the assay/autoclave
loading
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9
station 110) are maintained at a Grade C clean room environment, and the
autoclave unloading cell or station 114 is maintained at a Grade B clean room
environment. The shielding station 118 is maintained at a Grade C clean room
environment. The packaging stations 120 are maintained at a Grade D clean room
environment. Unless otherwise indicated, references to clean room
classifications
refer to clean room classifications according to Annex 1 of the European Union
Guidelines to Good Manufacturing Practice.
[0035] Additionally, the pressure within one or more stations of the
system 100 may be controlled at a negative or positive pressure differential
relative
to the surrounding environment and/or relative to adjacent cells or stations.
In
some embodiments, for example, all hot cells are maintained at a negative
pressure relative to the surrounding environment. Moreover, in some
embodiments, the isolator of the quality control testing station 116 is
maintained at
a positive pressure relative to the surrounding environment and/or relative to
adjacent stations of the system 100 (e.g., relative to the autoclave unloading
station 114).
[0036] FIG. 2 is a perspective view of an example radionuclide
generator 200 (specifically, an elution column assembly of a radionuclide
generator) that may be produced with the system 100. As shown in FIG. 2, the
radionuclide generator 200 includes an elution column 202 fluidly connected at
a
top end 204 to an inlet port 206 and a charge port (also referred to herein as
a fill
port or, more generally, an inlet port) 208 through an inlet line 210 and a
charge
line 212, respectively. A vent port 214 that communicates fluidly with an
eluant
vent 216 via a venting conduit 218 is positioned adjacent to the inlet port
206, and
may, in operation, provide a vent to a vial or bottle of eluant connected to
the inlet
port 206. The radionuclide generator 200 also includes an outlet port 220 that
is
fluidly connected to a bottom end 222 of the column 202 through an outlet line
224.
A filter assembly 226 is incorporated into the outlet line 224. The column 202
defines a column interior that includes a retaining media (e.g., alumina
beads, not
shown). As described above, during production of the radionuclide generator
200,
the column 202 is charged via the charge port 208 with a radioactive material,
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such as Molybdenum-99, which is retained with the interior of the column 202
by
the retaining media. The radioactive material retained by the retaining media
is
also referred to herein as the "parent radionuclide".
[0037] During use of the radionuclide generator 200, an eluant vial
(not shown) containing an eluant fluid (e.g., saline) is connected to the
inlet port
206 by piercing a septum of the eluant vial with the needle-like inlet port
206. An
evacuated elution vial (not shown) is connected to the outlet port 220 by
piercing a
septum of the elution vial with the needle-like outlet port 220. Eluant fluid
from the
eluant vial is drawn through the elution line, and elutes the column 202
containing
parent radionuclide (e.g., Mo-99). The negative pressure of the evacuated vial
draws eluant from the eluant vial and through the flow pathway, including the
column, to elute daughter radionuclide (e.g., Tc-99m) for delivery through the
outlet port 220 and to the elution vial. The eluant vent 216 allows air to
enter the
eluant vial through the vent port 214 to prevent a negative pressure within
the
eluant vial that might otherwise impede the flow of eluant through the flow
pathway. After having eluted daughter radionuclide from the column 202, the
elution vial is removed from the outlet port 220.
[0038] The radionuclide generator 200 shown in FIG. 2 is shown in
a finally assembled state. In particular, the radionuclide generator 200
includes an
inlet cap 228, an outlet cap 230, and a charge port cap 232. The caps 228,
230,
232 protect respective ports 206, 214, 220, and 208, and inhibit contaminants
from
entering the radionuclide generator 200 via the needles.
[0039] FIG. 3 is a schematic view of an example assay system 300
for assaying radionuclide generators 302, such as the radionuclide generator
200
shown in FIG. 2. The assay system 300 may be housed, for example, within the
assay/autoclave loading station 110 and, more specifically, within a hot cell
of the
assay/autoclave loading station 110.
[0040] The assay system 300 includes a radiation detection device
304, a fluid handling system 306, a connection interface 308, and a computing
device or controller 310. As described further herein, the assay system 300
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facilitates connecting radionuclide generators 302 directly to the radiation
detection
device 304 (i.e., without any intervening or intermediate transfer vials or
containers) for delivering eluates directly to the radiation detection device
304.
[0041] The radiation detection device 304 includes a collection
reservoir 312, and is configured to measure a radioactive content of a sample
within the collection reservoir 312. The radiation detection device 304 may
have
any suitable configuration that enables the assay system 300 to function as
described herein. In this embodiment, the radiation detection device 304 is a
dual,
concentric ionization chamber. One suitable embodiment of a dual, concentric
ionization chamber is described, for example, in U.S. Patent Application
Serial No.
15/203,452, filed July 6,2016, the disclosure of which is hereby incorporated
by
reference in its entirety. In this embodiment, the radiation detection device
304 is
configured to detect and/or measure electric current within first and second
ionization chambers of the radiation detection device 304 that correspond to a
radioactive content of a sample within the collection reservoir 312. The
controller
310 is configured to determine a radioactive content of the sample based on
the
current measurements.
[0042] The fluid handling system 306 is configured to deliver fluid
(e.g., eluate) to the collection reservoir 312. In particular, the fluid
handling system
306 includes a fluid supply line 314, a suction line 316, and a fluid
discharge line
318, each fluidly connected to the collection reservoir 312. As described in
more
detail herein, the fluid handling system 306 is configured generate a negative
pressure within the collection reservoir 312 via the suction line 316 such
that an
eluate from one of the radionuclide generators 302 is supplied to the
collection
reservoir 312 via the fluid supply line 314.
[0043] The connection interface 308 is configured to fluidly connect
at least one radionuclide generator 302, such as the radionuclide generator
200
shown in FIG. 2, to the collection reservoir 312 via the fluid handling system
306
such that eluate from the radionuclide generator 302 can be delivered to the
collection reservoir 312 via the fluid handling system 306. The connection
interface
308 includes an inlet port 320 for connecting to an inlet of a radionuclide
generator
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302 (e.g., inlet port 206 and/or charge port 208) and an outlet port 322 for
connecting to an outlet of the radionuclide generator 302 (e.g., outlet port
220).
The inlet and outlet ports 320, 322 may include, for example, septa that are
punctured or pierced by needle-like inlets and outlets of the radionuclide
generators 302. In this embodiment, the connection interface 308 is configured
for
connection to two radionuclide generators 302, including a first radionuclide
generator 324 and a second radionuclide generator 326. In particular, the
connection interface 308 includes two inlet ports 320 and two outlet ports
322. In
other embodiments, the connection interface 308 may be configured for
connection to more than or less than two radionuclide generators. In some
embodiments, for example, the connection interface 308 is configured for
connection to up to eight radionuclide generators.
[0044] The controller 310 is connected to the radiation detection
device 304 and components of the fluid handling system 306. The controller 310
is
configured to control components of the fluid handling system 306 to effect
delivery
of an eluate from the radionuclide generators 302 to the collection reservoir
312,
and to determine a radioactive content of the eluate within the collection
reservoir
312 based on measurements taken by the radiation detection device 304. While
the controller 310 is shown separate from other components of the assay system
300 in FIG. 3, it should be understood that components of the controller
(e.g., one
or more processors) may be located or integrated within other components of
the
assay system 300. In some embodiments, for example, a processor of the
controller 310 is integrated within the radiation detection device 304 for
determining the radioactive content of a sample within the collection
reservoir 312.
[0045] As shown in FIG. 3, each of the fluid supply line 314, the
suction line 316, and the fluid discharge line 318 extend into the collection
reservoir 312 of the radiation detection device 304. Moreover, the fluid
supply line
314, the suction line 316, and the fluid discharge line 318 extend to varying
depths
within the collection reservoir 312. Specifically, the fluid discharge line
318 extends
to the lowest depth and adjacent a lower surface of the collection reservoir
312 to
facilitate removing fluids from the collection reservoir 312. The suction line
316
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extends to the highest (i.e., shallowest) depth, and is positioned above a
liquid
reference line or plane 328 to inhibit liquid from being aspirated into the
suction
line 316. The fluid supply line 314 extends to a depth intermediate the
suction line
316 and the fluid discharge line 318.
[0046] In this embodiment, the fluid handling system 306 includes a
plurality of other fluid handling components for controlling the supply and
discharge
of fluids to and from the collection reservoir 312. For example, in the
example
embodiment, the fluid handling system 306 includes a vacuum pump 330, a
common discharge line 332, and a first valve 334 that provides selective fluid
communication between the vacuum pump 330 and each of the suction line 316
and the fluid discharge line 318 for performing the fluid handling operations
describes herein. In this embodiment, the fluid handling system 306 uses a
common vacuum pump 330 to generate suction in the suction line 316 and to draw
fluids through fluid discharge line 318. In other embodiments, the fluid
handling
system 306 may include separate, dedicated pumps and associated fluid handling
lines for each of the suction line 316 and the fluid discharge line 318.
Additionally,
in some embodiments, the vacuum pump 330 may be connected to one or more
liquid waste tanks in which radioactive liquid discharged from the collection
reservoir 312 is stored.
[0047] The vacuum pump 330 may have any suitable pump
configuration that enables the fluid handling system 306 to function as
described
herein. For example, the vacuum pump 330 may generally include, without
limitation, any vacuum pump capable of generating regulated, sustained vacuum
levels of 20 inHg or less.
[0048] The vacuum pump 330 is connected to the first valve 334 by
the common discharge line 332. The fluid discharge line 318 and the suction
line
316 are also each connected to the first valve 334. In the example embodiment,
the first valve 334 is a multi-port, multi-way valve that can be actuated
between a
plurality of different valve configurations to provide selective fluid
communication
between the fluid discharge line 318 and the vacuum pump 330, and selective
fluid
communication between the suction line 316 and the vacuum pump 330. For
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example, the first valve 334 can be actuated between a first valve
configuration, in
which the vacuum pump 330 is connected in fluid communication with the suction
line 316, and a second valve configuration, in which the vacuum pump 330 is
connected in fluid communication with the fluid discharge line 318.
[0049] Further, in the example embodiment, the fluid handling
system 306 includes a vent line 336 that is selectively connectable to the
fluid
discharge line 318 by actuation of the first valve 334. In particular, in the
example
embodiment, the first valve 334 can be actuated to a third valve configuration
in
which the vent line 336 is connected in fluid communication with the fluid
discharge
line 318, and the vacuum pump 330 is simultaneously connected in fluid
communication with suction line 316. The vent line 336 provides fluid
communication between the fluid discharge line 318 and an external environment
that has a pressure equal to or greater than the pressure within the
collection
reservoir 312. Thus, when the vacuum pump 330 is activated and the first valve
334 is in the third valve configuration (i.e., the vacuum pump 330 is
connected to
the suction line 316 and the vent line 336 is connected to the fluid discharge
line
318) gas (e.g., air) is drawn through the vent line 336 and into the
collection
reservoir 312 via the fluid discharge line 318. Other embodiments, such as the
embodiment shown in FIGS. 5-7, may not include a vent line 336.
[0050] In the example embodiment, the fluid handling system 306
also includes an eluant fluid source 338, a plurality of eluate supply lines
including
a first eluate supply line 340 and a second eluate supply line 342, a rinsing
fluid
reservoir 344, a rinsing fluid supply line 346, a second valve 348, and a
third valve
350.
[0051] The eluant fluid source 338 is connected to the connection
interface 308 for supplying eluant fluid (e.g., saline) to each of the
radionuclide
generators 302 during elution. The eluant fluid source 338 may include, for
example, one or more fluid reservoirs for holding the eluant fluid, a pump,
and a
fluid conduit for supplying eluant fluid to the one or more fluid reservoirs.
The fluid
reservoirs may include, for example and without limitation, a syringe barrel.
The
pump may have any suitable known pump configuration for pumping eluant fluid
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through the fluid conduit to fluid reservoir. In one embodiment, the pump is a
peristaltic pump.
[0052] The fluid reservoirs of the eluant fluid source 338 may be
connected in fluid communication with the radionuclide generators 302 via the
connection interface 308. In one embodiment, for example, the inlet of each
radionuclide generator 302 is connected to a corresponding fluid reservoir of
the
eluant fluid source 338 via the connection interface 308.
[0053] The first and second eluate supply lines 340, 342 are
connected to the connection interface 308 for supplying eluate from a
corresponding one of the radionuclide generators 302 connected thereto. The
first
and second eluate supply lines 340, 342 extend from the connection interface
308,
and are connected to the second valve 348.
[0054] The second valve 348 is connected between each of the
first and second eluate supply lines 340, 342 and the fluid supply line 314
for
providing selective fluid communication between the first and second eluate
supply
lines 340, 342 and the fluid supply line 314. The second valve 348 can be
actuated
to a first valve configuration in which fluid (specifically, eluate) from the
first eluate
supply line 340 is permitted to pass through the second valve 348, and fluid
from
the second eluate supply line is inhibited from passing through the second
valve
348. The second valve 348 can also be actuated to a second valve configuration
in
which fluid (specifically, eluate) from the second eluate supply line 342 is
permitted
to pass through the second valve 348, and fluid from the first eluate supply
line is
inhibited from passing through the second valve 348.
[0055] In the example embodiment, the third valve 350 is also
connected between the first and second eluate supply lines 340, 342 and the
fluid
supply line 314. More specifically, the third valve 350 is connected between
the
second valve 348 and the fluid supply line 314. Thus, in the example
embodiment,
the first and second eluate supply lines 340, 342 are selectively connectable
to the
fluid supply line 314 by actuation of the second valve 348 and the third valve
350
to supply eluate to the collection reservoir 312 from different radionuclide
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generators. In other embodiments, the first and second eluate supply lines
340,
342 may be selectively connectable to the fluid supply line 314 by actuation
of only
a single valve (e.g., second valve 348) to supply eluate to the collection
reservoir
from different radionuclide generators.
[0056] The third valve 350 is also connected between the rinsing
fluid supply line 346 and the fluid supply line 314 to provide selective fluid
communication between the rinsing fluid supply line 346 and the fluid supply
line
314. More specifically, the third valve 350 can be actuated to a first valve
configuration, in which fluid from the rinsing fluid supply line 346 is
permitted to
pass through the third valve 350, and a second valve configuration, in which
fluid
from one of the first and second eluate supply lines 340, 342 is permitted to
pass
through the third valve 350.
[0057] The rinsing fluid supply line 346 is also connected to the
rinsing fluid reservoir 344. In this embodiment, the rinsing fluid supply line
346 is
connected to the rinsing fluid reservoir 344 via the connection interface 308.
The
rinsing fluid reservoir 344 may include, for example and without limitation, a
syringe barrel. Suitable rinsing fluids that may be stored in the rinsing
fluid
reservoir 344 and used to rinse the collection reservoir 312 include, for
example
and without limitation, saline. In some embodiments, the rinsing fluid is the
same
fluid as the eluant fluid supplied by the eluant fluid source 338.
[0058] The first valve 334, the second valve 348, and the third
valve 350 may have any suitable valve configurations that enable the fluid
handling
system 306 to function as described herein, including, for example and without
limitation, pneumatically-actuated valves and electrically-actuated valves. In
the
example embodiment, each of the first valve 334, the second valve 348, and the
third valve 350 is a pneumatically-actuated valve connected to suitable
pressurized
gas source and the controller 310 to control operation of the valves. The
controller
310 is configured to control each of the first valve 334, the second valve
348, and
the third valve 350 by outputting control signals to the respective valve, and
thereby cause actuation of the respective valve. Pneumatically-actuated valves
suitable for use as the first valve 334, the second valve 348, and the third
valve
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350 include, for example and without limitation, Swagelok three-way valve
model
number SS-41GXES2-51D sold by Swagelok Company. In some embodiments,
the first valve 334 includes more than one valve, and may include, for
example,
two two-way valves or two three-way valves. In some embodiments, for example,
the first valve 334 may include two Swagelok two-way valves, model number SS-
92S2-C-NF-SI, or two Swagelok three-way valves, model number SS-41GXES2-
51D.
[0059] The controller 310 is connected to each of the vacuum
pump 330, the first valve 334, the second valve 348, and the third valve 350
to
control operation of the respective components to deliver fluids to the
collection
reservoir 312. The controller 310 is further connected to the radiation
detection
device 304 for receiving measurement data or values associated with a
radioactive
content of a sample (e.g., eluate) within the collection reservoir 312.
[0060] FIG. 4 is a block diagram of the controller 310. The
controller 310 includes at least one memory device 410 and a processor 415
that
is coupled to the memory device 410 for executing instructions. In this
embodiment, executable instructions are stored in the memory device 410, and
the
controller 310 performs one or more operations described herein by programming
the processor 415. For example, the processor 415 may be programmed by
encoding an operation as one or more executable instructions and by providing
the
executable instructions in the memory device 410.
[0061] The processor 415 may include one or more processing
units (e.g., in a multi-core configuration). Further, the processor 415 may be
implemented using one or more heterogeneous processor systems in which a
main processor is present with secondary processors on a single chip. As
another
illustrative example, the processor 415 may be a symmetric multi-processor
system containing multiple processors of the same type. Further, the processor
415 may be implemented using any suitable programmable circuit including one
or
more systems and microcontrollers, microprocessors, programmable logic
controllers (PLCs), reduced instruction set circuits (RISC), application
specific
integrated circuits (ASIC), programmable logic circuits, field programmable
gate
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arrays (FPGA), and any other circuit capable of executing the functions
described
herein. In this embodiment, the processor 415 controls operation of the fluid
handling system 306 by outputting control signals to components of the fluid
handling system 306, as described herein. Further, in this embodiment, the
processor 415 determines a radioactive content of a sample within the
collection
reservoir 312 based on data or measurements collected by the radiation
detection
device 304.
[0062] The memory device 410 is one or more devices that enable
information such as executable instructions and/or other data to be stored and
retrieved. The memory device 410 may include one or more computer readable
media, such as, without limitation, dynamic random access memory (DRAM),
static
random access memory (SRAM), a solid state disk, and/or a hard disk. The
memory device 410 may be configured to store, without limitation, application
source code, application object code, source code portions of interest, object
code
portions of interest, configuration data, execution events and/or any other
type of
data.
[0063] In this embodiment, the controller 310 includes a
presentation interface 420 that is connected to the processor 415. The
presentation interface 420 presents information, such as application source
code
and/or execution events, to a user 425, such as a technician or operator. For
example, the presentation interface 420 may include a display adapter (not
shown)
that may be coupled to a display device, such as a cathode ray tube (CRT), a
liquid crystal display (LCD), an organic LED (OLED) display, and/or an
"electronic
ink" display. The presentation interface 420 may include one or more display
devices. In this embodiment, the presentation interface 420 displays the
determined radioactive content of a sample within the collection reservoir
312,
such as a Molybdenum-99 content and/or a Technetium-99m content.
[0064] The controller 310 also includes a user input interface 430 in
this embodiment. The user input interface 430 is connected to the processor
415
and receives input from the user 425. The user input interface 430 may
include, for
example, a keyboard, a pointing device, a mouse, a stylus, a touch sensitive
panel
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(e.g., a touch pad or a touch screen), a gyroscope, an accelerometer, a
position
detector, and/or an audio user input interface. A single component, such as a
touch screen, may function as both a display device of the presentation
interface
420 and the user input interface 430.
[0065] In this embodiment, the controller 310 further includes a
communication interface 435 connected to the processor 415. The communication
interface 435 communicates with one or more remote devices, such as the fluid
handling system 306 and the radiation detection device 304.
[0066] In operation, the radionuclide generators 302 are connected
to the fluid handling system 306 via the connection interface 308, and are
eluted
directly into the collection reservoir 312 (i.e., without any intervening
transfer vials
or containers) to measure or assay the eluate of each radionuclide generator
302.
[0067] The radionuclide generators 302 may be connected to the
connection interface 308 by manually moving or manipulating the radionuclide
generators 302 to a position adjacent the connection interface 308 using, for
example, telemanipulators. In some embodiments, the radionuclide generators
302
are connected to the connection interface 308 by piercing inlet and outlet
septa of
the connection interface 308 with corresponding inlet and outlet needles of
each of
the radionuclide generators 302. Further, in this embodiment, the radionuclide
generators 302 are concurrently connected to the connection interface 308.
[0068] The controller 310 controls operation of the fluid handling
system 306 to elute the radionuclide generators 302, and deliver eluates to
the
collection reservoir 312. In this embodiment, the controller 310 controls
operation
of the first valve 334, the second valve 348, the third valve 350, and the
vacuum
pump 330 to sequentially elute the first and second radionuclide generators
324,
326 into the collection reservoir 312, and to remove or discharge fluids from
the
collection reservoir 312 between sequential elutions.
[0069] Specifically, in this embodiment, the controller 310 actuates
each of the second valve 348 and the third valve 350 to respective valve
configurations such that the first eluate supply line 340 is connected in
fluid
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communication with the collection reservoir 312 via the fluid supply line 314.
The
controller 310 further actuates the first valve 334 to a valve configuration
such that
the vacuum pump 330 is connected in fluid communication with the suction line
316, and thereby configured to generate a negative pressure within the
collection
reservoir 312 via the suction line 316. The controller 310 then activates the
vacuum pump 330 to generate a negative pressure within or evacuate the
collection reservoir 312 via the suction line 316. The negative pressure
within the
collection reservoir 312 causes eluant fluid from the eluant fluid source 338
to be
drawn through the first radionuclide generator 324 to elute the first
radionuclide
generator 324. The resulting eluate is drawn or directed through the first
eluate
supply line 340 and the fluid supply line 314 into the evacuated collection
reservoir
312.
[0070] In this embodiment, the controller 310 elutes the first
radionuclide generator 324 until a predetermined or fixed volume of eluant
fluid is
drawn through the first radionuclide generator 324. The volume of eluant fluid
drawn through the first radionuclide generator 324 may be in the range of, for
example, 1 milliliter (mL) to 50 mL, 2 mL to 75 mL, 5 mL to 25 mL, 5 mL to 15
mL,
7 mL to 35 mL, 7 mL to 15 mL, and 10 mL to 20 mL.
[0071] The controller 310 activates the vacuum pump 330 until the
entire volume of eluant fluid is drawn through the first radionuclide
generator 324.
Once the elution is complete, the controller 310 deactivates the vacuum pump
330.
In some embodiments, the fluid handling system 306 may include one or more
sensors connected to the controller 310 for detecting or determining when the
entire volume of eluant fluid has been drawn through the first radionuclide
generator 324. In some embodiments, for example, the fluid handling system 306
includes a bubble or gas sensor connected to the first eluate supply line 340
to
detect bubbles or gas within the first eluate supply line 340. The presence of
gas
or bubbles within the first eluate supply line 340 indicates that the fixed
volume of
fluid has been drawn through the first radionuclide generator 324, and there
is little
or none of the fixed volume of eluant fluid remaining. The fluid handling
system
306 may include similar sensors connected to the second eluate supply line
342.
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[0072] When elution of the first radionuclide generator 324 is
complete, the radiation detection device 304 measures the radioactive content
of
the eluate within the collection reservoir 312. In this embodiment, the
radiation
detection device 304 measures the radioactive content of the eluate by
measuring
electric current values in one or more ionization chambers of the radiation
detection device 304, where the magnitude of the measured current corresponds
to the radioactive content of the eluate. The controller 310 determines the
radioactive content of the eluate (e.g., a Molybdenum-99 content and/or a
Technetium-99m content) based on the current values measured by the radiation
detection device 304.
[0073] The eluate from the first radionuclide generator 324 is
removed or discharged from the collection reservoir 312 prior to elution of
the
second radionuclide generator 326. Specifically, in this embodiment, the
controller
actuates the first valve 334 to a valve configuration in which the vacuum pump
330
is connected in fluid communication with the fluid discharge line 318, and
activates
the vacuum pump 330 to aspirate eluate within the collection reservoir 312
into the
fluid discharge line 318. Fluids from the fluid discharge line 318 are
directed to a
radioactive liquid waste container for further processing and disposal. In
some
embodiments, the vent line 336 may also be connected in fluid communication
with
the suction line 316 (via the first valve 334) during removal of liquid from
the
collection reservoir 312 to facilitate removal of liquid from the collection
reservoir
312.
[0074] The second radionuclide generator 326 is assayed in the
same manner as the first radionuclide generator 324, except the second valve
348
is actuated to a valve configuration in which the second eluate supply line
342 is
connected in fluid communication with the fluid supply line 314. The
controller 310
then controls operation of the fluid handling system 306 and the radiation
detection
device 304 to elute the second radionuclide generator 326 into the collection
reservoir 312, and assay the eluate of the second radionuclide generator 326.
If
the assay results of one or more of the radionuclide generators 302 are out of
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specification (e.g., not within a predefined range), the radionuclide
generator may
be pulled from the production line for further processing, analysis, and/or
disposal.
[0075] In some embodiments, the radiation detection device 304
may be calibrated or "tared" between subsequent elutions to account for
background radiation that may be present in the radiation detection device
304.
For example, after an assay sample is removed from the collection reservoir
312,
the empty collection reservoir 312 is assayed for Tc-99m and Mo-99 content.
The
measured values may be stored (e.g., in the memory device 415) and then used
as a baseline or "tare" for the subsequent elution analysis.
[0076] In some embodiments, the collection reservoir 312 may be
washed or rinsed with a rinsing fluid (e.g., saline), for example, in between
elutions
of different radionuclide generators or after a batch of radionuclide
generators
have been assayed. In this embodiment, for example, following elution of one
or
more radionuclide generators into the collection reservoir 312, the controller
310
actuates the third valve 350 to a valve configuration in which the rinsing
fluid
supply line 346 is connected in fluid communication with the fluid supply line
314,
and actuates the first valve 334 to a valve configuration in which the vacuum
pump
330 is connected in fluid communication with the suction line 316. The
controller
310 then activates the vacuum pump 330 to generate a negative pressure within
the collection reservoir 312, thereby drawing rinsing fluid from the rinsing
fluid
reservoir 344 through the rinsing fluid supply line 346 and the fluid supply
line 314,
and into the collection reservoir 312.
[0077] Further, in this embodiment, after the rinsing fluid is
delivered to the collection reservoir 312, the controller 310 controls the
fluid
handling system 306 to draw gas bubbles through the rinsing fluid to agitate
the
rinsing fluid and facilitate cleaning of the collection reservoir 312.
Specifically, the
controller 310 actuates the first valve 334 to a valve configuration in which
the fluid
discharge line 318 is connected in fluid communication with the vent line 336,
and
in which the vacuum pump 330 is connected in fluid communication with the
suction line 316. The controller 310 then activates the vacuum pump 330 to
generate a negative pressure within the collection reservoir 312, thereby
drawing
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gas (e.g., air) through the vent line 336 and the fluid discharge line 318,
and
through the rinsing fluid within the collection reservoir 312. The rinsing
fluid is
subsequently removed from the collection reservoir 312 by connecting the fluid
discharge line 318 to the vacuum pump 330, and activating the vacuum pump 330
to aspirate the rinsing fluid into the fluid discharge line 318.
[0078] FIG. 5 is a top plan view of another embodiment of an
example assay system 500 suitable for use in a radionuclide generator
manufacturing system, such as the system 100 shown in FIG. 1. The assay
system of FIG. 5 includes components similar to the components of the assay
system 300 shown and described above with reference to FIG. 3. For example,
the
assay system 500 includes a radiation detection device 502, a fluid handling
system 504, a connection interface 506, and a controller (not shown in FIG.
5).
Additionally, the assay system 500 includes a plurality of pneumatic supply
lines
507 for supplying pressurized gas to pneumatically-actuated valves of the
assay
system 500.
[0079] In this embodiment, the assay system 500 is designed to
assay multiple radionuclide generators at the same time (i.e.,
simultaneously).
Specifically, the assay system 500 includes a plurality of the radiation
detection
devices 502 and a plurality of fluid handling subsystems 508, each configured
to
control the supply of fluid (e.g., eluate) to and from a respective one of the
radiation detection devices 502. The example embodiment includes four
radiation
detection devices 502, and four fluid handling subsystems 508. Other
embodiments may include more or less than four radiation detection devices 502
and four fluid handling subsystems 508. Further, in this embodiment, each
fluid
handling subsystem 508 is configured to supply an eluate from two different
radionuclide generators to a common radiation detection device 502. In other
embodiments, one or more of the fluid handling subsystems 508 may be
configured to supply an eluate from more than or less than two radionuclide
generators to a radiation detection device.
[0080] The assay system 500 of FIG. 5 also includes a secondary
or redundant connection interface 510 that is selectively connectable to the
fluid
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handling system 504 via a connection block 512 connected to a lever arm 514.
In
operation, only one of the connection interface 506 and the secondary
connection
interface 510 is connected to the fluid handling system 504 via the connection
block 512.
[0081] Further, in this embodiment, the connection block 512
includes a disposable portion 516 that is connected to the connection
interface 506
(specifically, outlet ports of the connection interface 506) via disposable
tubing,
such as silicone tubing (not shown in FIG. 5). The disposable portion 516 and
disposable tubing are designed to be discarded after a batch of radionuclide
generators (e.g., eight) is assayed with the assay system 500.
[0082] FIG. 6 is a perspective view of the connection interface 506
of the assay system 500 shown in FIG. 5. The secondary connection interface
510
has an identical configuration to the connection interface 506. The connection
interface 506 is configured to fluidly connect a plurality of radionuclide
generators
602 to the collection reservoirs of the radiation detection devices 502 such
that
eluate from the radionuclide generators 602 can be directly delivered to the
collection reservoirs via the fluid handling system 504. As shown in FIG. 6,
in this
embodiment, the connection interface 506 is configured for connection to eight
radionuclide generators 602. Specifically, the connection interface 506
includes
eight inlet ports 604 for connecting to the inlet of a radionuclide generator,
and
eight outlet ports 606 for connecting to an outlet of the radionuclide
generator. In
this embodiment, each inlet port 604 and each outlet port 606 includes a
septum
configured to be pierced by a corresponding inlet needle or outlet needle of a
radionuclide generator.
[0083] A plurality of eluate supply lines 608 are connected to the
outlet ports 606 of the connection interface 506. Only a portion of each
eluate
supply line 608 is shown in FIG. 6. Further, a bubble sensor 610 is connected
to
each of the eluate supply lines 608 for detecting the presence of gas or
bubbles
within the respective eluate supply line 608.
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[0084] Referring again to FIG. 5, in this embodiment, the fluid
handling system 504 includes two eluant fluid sources 518, one for each of the
connection interfaces 506, 510. Each of the eluant fluid sources 518 is
connected
to a respective one of the connection interfaces 506, 510 for supplying eluant
fluid
(e.g., saline) to each of the radionuclide generators 602 during elution. In
this
embodiment, each of the eluant fluid sources 518 includes a plurality of fluid
reservoirs 520 for holding the eluant fluid, a pump (not shown in FIG. 5), and
a
fluid conduit 522 for supplying eluant fluid to the fluid reservoirs 520. The
fluid
reservoirs from the eluant fluid source 518 of the secondary connection
interface
510 are not shown in FIG. 5.
[0085] As shown in FIG. 6, in this embodiment, the fluid reservoirs
520 are syringe barrels configured to hold a fixed amount of eluant fluid
(e.g., 10
mL). Further, in this embodiment, each eluant fluid source 518 includes 8
fluid
reservoirs 520, although other embodiments may include more or less than 8
fluid
reservoirs. The fluid reservoirs 520 of the eluant fluid source 518 are
connected in
fluid communication with the radionuclide generators 602 via the connection
interface 506. In this embodiment, the inlet of each radionuclide generator
602 is
connected to a corresponding fluid reservoir 520 via the connection interface
506.
[0086] FIG. 7 is an enlarged view of one of the fluid handling
subsystems 508 of the fluid handling system 504 shown in FIG. 5. With the
exception of the vent line 336 and the associated venting operations, each of
the
fluid handling subsystems 508 includes substantially the same components and
operates in substantially the same manner as the fluid handling system 306
described above with reference to FIG. 3. Specifically, in this embodiment,
each
fluid handling subsystem 508 includes a fluid supply line 702, a suction line
704, a
fluid discharge line 706, a common discharge line 708, a first valve 710, a
first
eluate supply line 712, a second eluate supply line 714, a rinsing fluid
supply line
716, a second valve 718, and a third valve 720. Each of the fluid supply line
702,
the suction line 704, and the fluid discharge line 706 are fluidly connected
to the
collection reservoir of a corresponding radiation detection device 502. The
first
valve 710, the second valve 718, and the third valve 720 operate in the same
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manner as the first valve 334, the second valve 348, and the third valve 350
of the
fluid handling system 306 described above with reference to FIG. 3 to carry
out the
fluid handling operations described herein.
[0087] In this embodiment, the eluate supply lines 712 and 714 of
each fluid handling subsystem 508 are constructed of small inner diameter
(e.g.,
1/8 of an inch or less) tubing to minimize or reduce liquid hold up between
the
radionuclide generator 602 and the collection reservoir of a corresponding
radiation detection device 502. Further, the tubing is sloped downward along
the
flow path to facilitate fluid flow towards the collection reservoir and to
reduce or
minimize liquid hold-up between the radionuclide generator 602 and the
collection
reservoir.
[0088] In this embodiment, the fluid handling system 504 includes a
single vacuum pump. The vacuum pump is connected to the first valve 710 of
each
fluid handling subsystem 508 to enable selective fluid communication between
the
suction line 704 of each fluid handling subsystem 508 and the vacuum pump, and
the fluid discharge line 706 of each fluid handling subsystem 508 and the
vacuum
pump.
[0089] In operation, each of the radionuclide generators 602 is
connected to the fluid handling system 504 via the connection interface 506,
and is
eluted directly (i.e., without any intervening transfer vials or containers)
into the
collection reservoir of one of the radiation detection devices 502. In this
embodiment, the controller of the assay system 500 controls operation of the
fluid
handling system 504 to simultaneously elute four of the radionuclide
generators
602 directly into four corresponding radiation detection devices 502.
Specifically,
the controller controls operation of the first valve 710, the second valve
718, and
the third valve 720 of each of the fluid handling subsystems 508, along with
the
vacuum pump, to elute four of the radionuclide generators 602, and deliver an
eluate from each of the four radionuclide generator 602 into the collection
reservoir
of a respective radiation detection device 502.
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[0090] Each of the radiation detection devices 502 then measures
the radioactive content of the eluate within the corresponding collection
reservoir,
and the controller determines the radioactive content of each eluate based on
the
measurements taken by the radiation detection devices 502. In this embodiment,
the radiation detection device 502 and/or the controller determines both a
Molybdenum-99 content and a Technetium-99m content of each eluate. Once the
assay process on the first four radionuclide generators is completed, the
controller
controls operation of the fluid handling system 504 to elute the other four
radionuclide generators into four corresponding radiation detection devices to
assay the remaining radiation nuclide generators.
[0091] Referring again to FIG. 5, in this embodiment, each radiation
detection device 502 includes and/or is connected to a radiation-shielding
plug 524
to prevent external radiation from entering the radiation detection device
502. The
tops of the radiation-shielding plugs 524 are shown in FIGS. 5 and 7.
[0092] FIG. 8 is a sectional view of one of the radiation-shielding
plugs 524 connected to a collection reservoir 802 of one of the radiation
detection
devices 502 shown in FIG. 5. The radiation-shielding plug 524 includes a
cylindrical housing 804 constructed of radiation shielding material. Suitable
radiation shielding materials from which the cylindrical housing 804 may be
constructed include, for example and without limitation, lead, depleted
uranium,
and tungsten.
[0093] The cylindrical housing 804 has an interior cavity 806
through which the fluid supply line 702, the suction line 704, and the fluid
discharge line 706 extend. The interior cavity 806 is filled with radiation
shielding
material (e.g., molten lead, not shown in FIG. 8) to provide radiation
shielding.
Further, as shown in FIG. 8, the point at which each of the lines 702, 704,
706
enters the plug 524 is axially offset relative to the point at which each of
the lines
702, 704, 706 exits the plug to avoid forming a shine path that would allow
external
radiation to stream directly into the radiation detection device 502 and
affect assay
measurements.
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[0094] In this embodiment, the collection reservoir 802 threads into
a tungsten fixture 808, and seals against an elastomeric gasket 810. In other
embodiments, the collection reservoir 802 may be connected to the radiation-
shielding plug 524 using any suitable connection means. Further, in this
embodiment, the collection reservoir 802 is constructed from Type 1
borosilicate
glass, and is coated with a Diamon-Fusion coating to facilitate reducing
adhesion
of eluate to the collection reservoir 802. In other embodiments, the
collection
reservoir 802 may be constructed of other materials.
[0095] As shown in FIG. 8, each radiation detection device 502
also includes a constancy check device 812 to ensure proper functioning of the
radiation detection device 502. In this embodiment, the constancy check device
812 includes a telescopic rod 814 that extends through the cylindrical housing
804.
The telescopic rod 814 includes an outer rod 816 and an inner rod 818 that
telescopes or moves relative to the outer rod 816. A radiation element or
source
820 having a known level of radioactivity is connected to a distal end of the
inner
rod 818. In this embodiment, the radiation source 820 includes a Cesium-137
pellet. The inner rod 818 is moveable relative to the outer rod 816 between a
retracted position (shown in FIG. 8), in which the radiation source 820 is
positioned
within the radiation-shielding plug 524, and an extended position in which the
radiation source 820 is positioned within an ionization chamber of the
radiation
detection device.
[0096] When the radiation source 820 is positioned within the
ionization chamber of the radiation detection device 502, the radiation
detection
device 502 measures the known radiation level of the radiation source 820. The
known background radiation may be subtracted out of the radiation measurement
to facilitate accurate measurement results. The radiation level measured while
the
radiation source 820 is positioned within the ionization chamber of the
radiation
detection device can be used to determine if the radiation detection device
502 is
performing radiological measurements accurately (e.g., by comparing the
measured values to the known level of radioactivity of the radiation source
820). In
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some embodiments, the constancy check device 812 is used to perform daily
constancy checks.
[0097] Embodiments of the assay systems and methods described
herein provide several advantages over known systems. For example,
embodiments described herein facilitate assaying radionuclide generators
without
the use of transfer vials or containers, thereby reducing or eliminating costs
associated with the manufacture and use of sterile evacuated vials typically
used
in performing assay procedures. Additionally, because transfer vials are not
used,
systems and methods of the present disclosure facilitate reducing solid
radiological
waste and remedial processing steps as compared to typical assay procedures.
Further, embodiments of the systems and methods provide an automated assay
procedure in which an automated fluid handling system elutes one or more
radionuclide generators directly into a collection reservoir of radiation
detection
device, thereby eliminating multiple material handling steps associated with
typical
assay procedures that use transfer vials. Thus, embodiments of the systems
described herein can operate autonomously, without personnel involvement.
Additionally, embodiments of the vial-less assay systems and methods have
relatively little or no moving parts as compared to systems that rely on
transfer
vials to assay radionuclide generators, which facilitates reducing or
minimizing
mechanical process failures. Further, embodiments of the systems and the
methods described herein facilitate improving throughput by increasing the
number
of radionuclide generators that can be assayed within a given space and a
given
amount of time. For example, systems and methods described herein can process
four radionuclide generators simultaneously, whereas typical, vial-based
systems
would have roughly half this throughput.
[0098] When introducing elements of the present invention or the
embodiment(s) thereof, the articles "a", "an", "the" and "said" are intended
to mean
that there are one or more of the elements. The terms "comprising",
"including" and
"having" are intended to be inclusive and mean that there may be additional
elements other than the listed elements.
CA 03049013 2019-07-02
WO 2018/136078 30
PCT/US2017/014316
[0099] As various changes could be made in the above
constructions and methods without departing from the scope of the invention,
it is
intended that all matter contained in the above description and shown in the
accompanying drawings shall be interpreted as illustrative and not in a
limiting
sense.
