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Separation Science and Technology
ISSN: 0149-6395 (Print) 1520-5754 (Online) Journal homepage: https://www.tandfonline.com/loi/lsst20
Microfluidics-based separation of actinium-225
from radium-225 for medical applications
Sandra Davern, David O’Neil, Hannah Hallikainen, Kathleen O’Neil, Steve
Allman, Larry Millet, Scott Retterer, Mitchel Doktycz, Robert Standaert, Rose
Boll, Shelley Van Cleve, David DePaoli & Saed Mirzadeh
To cite this article: Sandra Davern, David O’Neil, Hannah Hallikainen, Kathleen O’Neil,
Steve Allman, Larry Millet, Scott Retterer, Mitchel Doktycz, Robert Standaert, Rose Boll,
Shelley Van Cleve, David DePaoli & Saed Mirzadeh (2019): Microfluidics-based separation of
actinium-225 from radium-225 for medical applications, Separation Science and Technology, DOI:
10.1080/01496395.2019.1614956
To link to this article: https://doi.org/10.1080/01496395.2019.1614956
Published online: 20 May 2019.
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Microfluidics-based separation of actinium-225 from radium-225 for medical
applications
Sandra Davern
a
, David O’Neil
b
, Hannah Hallikainen
b,d
, Kathleen O’Neil
b
, Steve Allman
c
, Larry Millet
c,e
,
Scott Retterer
c,f
, Mitchel Doktycz
c,f
, Robert Standaert
c,g
, Rose Boll
a
, Shelley Van Cleve
a
,
David DePaoli
a
, and Saed Mirzadeh
a
a
Isotope and Fuel Cycle Technology Division, Oak Ridge National Laboratory, Oak Ridge, USA;
b
Oak Ridge Associated Universities, Oak Ridge,
TN;
c
Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN, USA;
d
Arizona State University, Tempe, USA;
e
Joint Research
Activity, Bredesen Center, University of Tennessee, TN, USA;
f
Center for Nanophase Materials Sciences Division, Oak Ridge National
Laboratory, Oak Ridge, USA;
g
Chemistry, East Tennessee State University, Johnson City, USA
ABSTRACT
Separation of
225
Ra (t
1/2
= 15 d) from its daughter isotope
225
Ac (t
1/2
= 10 d) is necessary to obtain
pure
225
Ac for cancer alpha-therapy. In this study, microscale separation of
225
Ra from its daughter
225
Ac using BioRad AG50X4 cation exchange resin was achieved with good reproducibility across
microdevices, and ≥90% purity was achieved for
225
Ac, which is comparable to conventional
chromatography. These results indicate the potential for greater use of microfluidics for biome-
dical radiochemistry. The modularity of the system and its compatibility with different resins
allows for quick and easy adaptation to the various needs of a separation campaign.
ARTICLE HISTORY
Received 23 December 2018
Accepted 1 May 2019
KEYWORDS
Microfluidics; Actinium-225;
Radium-225; Ion
chromatography; Targeted-
Alpha-Therapy
Introduction
Radioisotopes have applications for medicine, industry,
and basic scientific research in areas such as super heavy
elements and for the advancement of knowledge about
the periodic table of elements.
[1–4]
Many of these radio-
isotopes are limited in quantity and expensive, and gen-
erally they can only be handled in gloveboxes and/or hot
cells. Many different types of ion-exchange and extrac-
tion resins have been applied during extensive chemical
separations for the purpose of obtaining radioisotopes of
interest. With advancements in microfabrication and
technologies for scaling-down and automating chemical
separations, the ability to capture, store, and release
custom-made radioisotopes on an increasingly smaller
scale is within reach. Research on microfluidic purifica-
tion strategies has the potential to open new opportu-
nities for isotope preparations on small scales.
Microfluidic generators and separators can improve the
delivery of small quantities of radioisotopes and enable
the production of customized doses for medical applica-
tions. Through this approach, the microfluidic separa-
tion of radioisotopes has the potential to increase the
availability of rare and expensive isotopes, limit radiolo-
gical exposure of personnel, and improve the efficiency
of the research and development efforts that can be
performed in radiological fume hoods while allowing
expensive hot cells to be kept free for production efforts.
Current expanding interest in the application of alpha
and beta emitting radioisotopes such as
223
Ra,
225
Ac,
213
Bi,
and
177
Lu for cancer therapy is driving research into the
production and application of these isotopes.
[5–9]
For exam-
ple,
225
Ac can serve as a generator for
213
Bi production, thus
creating two lines of alpha therapeutics from a single
225
Ac
source.
[10–13]
Both
225
Ac and
213
Bi have short half-lives of
10 days and 45.6 min respectively, and both of them decay
by alpha emission. These factors make
255
Ac and
213
Bi
highly effective for treating small metastatic cancers. To
improve treatment outcomes, the therapeutic effectiveness
of these alpha emitters may be increased by targeting the
radioisotopes directly to tumor sites. Antibodies, peptides,
and other biomolecules that selectively recognize cancer
cells enable delivery of the radiotherapeutic alpha particle
to diseased cells and tissues. There, the short pathlength and
high energy deposition of alpha particles produce numer-
ousdouble-strandDNAbreaksthatareefficientlydestruc-
tive to living cells.
[14,15]
The intended outcome of radiation
therapy is to impose critical damage to cancerous tissues
while minimizing exposures to healthy tissues; in general,
healthy tissues have a greater propensity to recover from
radiation-induced damage than many cancer cells due to
theirslowerreplicationrates.
[16–21]
CONTACT Sandra Davern davernsm@ornl.gov Isotope and Fuel Cycle Technology Divisions
This article has been republished with minor changes. These changes do not impact the academic content of the article.
SEPARATION SCIENCE AND TECHNOLOGY
https://doi.org/10.1080/01496395.2019.1614956
© 2019 Taylor & Francis Group, LLC
Due to successful clinical trials using
225
Ac as a cancer
therapeutic,
[22]
maintaining and improving
225
Ac avail-
ability is crucial to allow individuals access to much
needed treatments. Recently, efforts to produce
225
Ac
have focused on the high energy proton irradiation of
232
Th targets using linear accelerators.
[13,23–25]
However,
the most common method of production of
225
Ac for
clinical trials is via the decay of the long-lived
229
Th
(t
1/2
= 7932 yr). Thorium-229 decays to
225
Ac via the
intermediate
225
Ra, and separation of these two isotopes
is a necessary step in the purification process.
[11]
The
conventional columns used for this process include two
AG50X4 columns with 4 mL and 0.4 mL bed volumes
(BVs), each column removing ~90%
225
Ra, with the final
225
Ac sample having <1%
225
Ra impurity.
[11]
This con-
ventional ion-exchange resin was successfully adapted to
a microfluidic format with BVs on the order of 80-fold
less than those typically used.
[11]
The equivalent separa-
tions achieved using our microfluidic ion-exchange plat-
form clearly demonstrates the potential of this approach
for future novel separations chemistry using rare and or
expensive radioisotopes. Decreasing the quantity of radio-
isotope required for novel separations chemistry will
increase research opportunities among a wider pool of
researchers. This microfluidic chromatographic process
can also be applied to the use of expensive extraction
resins such as the Eichrom® Normal DGA (N,N,N’,N’-
tetrakis-2-ethylhexyl-diglycolamide) and Branched
(B-DGA) resins for radioisotopes separations. In this
case, limiting the amount of resin used is important due
to their cost, as is controlling fluid flow since these extrac-
tion resins are notoriously slow under gravity-flow opera-
tions. Further, the process has been automated to add
greater control over the flow rate, and eluent volume
while allowing improved throughput by monitoring the
separation in real-time, to allow efficient collection of the
eluted product. Automation of the separation process has
the added advantage of reducing worker exposure
(increased distance from radiation source) and improving
reproducibility (by controlling the fluid flow and moni-
toring the real-time elution) of ion-exchange separations.
Materials and methods
Microfluidic masters were fabricated through conventional
photolithographic processes using quartz-chrome masks,
AZTFP-650 photoresist, and 1.0 µm thermal silicon diox-
ide-coated silicon wafers as detailed previously.
[26]
Microscale chambers for microfluidic separations were cre-
ated through replica molding with polydimethylsiloxane
(PDMS) (Sylgard 184 two-part kit). The PDMS pre-
polymer and curing agents were combined at a 10:1 ratio,
mixed (5 min) and poured in a two-stage process. First
liquid PDMS was placed at the base of the Helix silastic
medical tubing segments that were temporarily held in place
(Duco Cement) on the silanized wafer, and then it was cured
(70°C, 15 min). After curing the tubing in place with PDMS,
liquid PDMS was poured across the wafer and degassed
under vacuum before the second application of PDMS was
cured (70°C, 30 min). PDMS replicas were removed from
the wafer, and the dry glue plugs were removed from the
tube segments. The PDMS was trimmed and cleaned with
Scotch tape before plasma treatment and annealing (70°C,
20 min) to plasma-cleaned microscope slides.
Packing microfluidics with chromatographic separa-
tion media for
225
Ra and
225
Ac separation was performed
in a manner similar to that described in the previously
published process.
[26]
The assembled microfluidic plat-
form was prepared for fluid injection by holding the
microfluidics under vacuum (5–10 min) to degas the
PDMS elastomer material. After returning the microflui-
dics to the room atmosphere, water was injected into the
microfluidic through one of the helix tubing ports. First
the separation media, AG50X4 resin, was resized with cell
strainers to retain beads in the 40–70 µm size range. Then
the resized resin beads were inserted into the bed to
ensure uniform distribution and packing.
[26]
The filtered
resin was then conditioned with 150 µL, (3 BVs) of 8 M
HNO
3
under gravity flow through the device, followed by
a column wash with 250 µL (5 BVs) of 0.1 M HNO
3
.
Finally, packed and equilibrated microfluidic columns
were stored in 0.1 M HNO
3
until ready for use.
For
225
Ra and
225
Ac separations, a mixed solution of
225
Ra/
225
Ac (5–12 µCi) in a 0.1 M HNO
3
solution was
loaded using gravity flow. The resin was washed with
250 µL (5 BVs) of 0.1 M HNO
3
. Controlled elution was
achieved by using a syringe pump set to a flow rate of
20 µL per minute. Three separate microfluidic devices
were fabricated, packed with resin, and used to deter-
mine the reproducibility of the
225
Ra/
225
Ac separation
process in the semi-automated system.
To elute
225
Ra, the loop was loaded with 500 µL (10
BVs) of 1.2 M HNO
3
, and 50 µL (1 BVs) fractions were
collected every two and a half minutes for 30 minutes. To
elute
255
Ac, the loop was loaded with 10 BVs (500 µL) of
8 M HNO
3
, and 1 BV (50 µL) fractions were collected
every two and a half minutes for 30 min. Fractions were
analyzed in real time using a Canberra Cadmium Zinc
Telluride (CZT) detector monitoring a window of 20–-
60 keV for
225
Ra (40.3 keV γ-ray, 30.0% intensity) and
200–240 keV for
225
Ac (217.6 keV, 11.6% intensity from
4.9 m
221
Fr α-decay daughter). Counts were verified for
each fraction using a Canberra sodium iodide gamma-ray
detector and the associated Genie software monitoring
two windows set at 35–60 keV for
225
Ra and 200–240 keV
for
225
Ac. The amount of
225
Ra and
225
Ac in each of the
2S. DAVERN ET AL.
eluents was determined by expressing the total activity in
the each of the eluent fractions (1.2 M and 8 M HNO
3
)as
a percentage of the total activity for all fractions collected.
Column performance was evaluated by measuring
resolution (R), which is defined as the quotient of two
times the difference of the elution volumes (
225
Ra and
225
Ac) and the sum of the base widths of the elution
peaks, with units expressed in microliters:
R¼2V225Ac V225Ra
ðÞ=W225Ra þW225Ac
ðÞ(1)
Results and discussion
Radiochemical separations are essential to obtaining
highly purified radioisotopes of interest. Many different
types of ion-exchange and extractions resins have been
used for this purpose. Few studies have examined the
applicability of scaling radiochemical separations to the
microscale.
[27–29]
The majority of such studies has
focused on the miniaturization of production and synth-
esis of short-lived positron-emitting radioisotopes and
corresponding biomolecule synthesis for applications in
positron emission tomography (PET) such as
18
F-fluorodeoxyglucose (
18
F-FDG).
[30–33]
Microfluidic
separation platforms were previously developed to purify
recombinant proteins produced from bacterial extracts
and cell-free protein synthesis reactions (Fig. 1).
[26]
Here,
the size and access ports of the microfluidic platforms
were tailored to improve the packing process of chro-
matographic media and for inserting the microfluidic
module into an in-line process for radiochemical ion-
exchange separations.
Specifically, conventional column chromatography for
the radiochemical separation of
225
Ra from its daughter
isotope
225
Ac was down-scaled 80-fold to a microfluidic
BV capacity (Fig. 1). PDMS, a silicone-based organic
polymer, was used to fabricate microfluidic ion-
exchange columns of 12 and 55 µL BVs. PDMS is highly
resistant to many solvents and acids. For example, PDMS
has previously been reported to withstand exposure to
concentrated nitric acid with minimal leaching in a 24 h
period.
[34–36]
In contrast, PDMS can be etched with sul-
furic acid and other solvents.
[37,38]
Each microfluidic ion-
exchange column has a resin loading port, in addition to
inlet and outlet ports. Silicone master wafers were first
prepared using a photolithography method to etch the
template. The PDMS was poured onto these wafer tem-
plates with silicone tubing positioned at the inlet, outlet,
and loading ports. The PDMS was allowed to cure to
prepare the microscale chromatography columns.
[26]
The retaining posts of these microscale columns were
spaced 40 µm apart (Fig. 2b), so the beads were sized to
exclude those less than 40 µm. Resin beads below this size
could escape into the microfluidic channels arrayed along
the edge of the device adjacent to the resin-retaining posts
(Fig. 2c). Beads larger than ~70–100 µm are difficult to
load into the microfluidic device and promote the devel-
opment of voids, thus compromising an efficiently packed
resin. Themicrofluidic channel height was on the order of
120 µm, which allowed for a maximum stacking of 2–3
beads across the length of the device. Layering of AG50X4
beads within a microfluidic device was observed as shown
in Fig. 2d, and an example of the efficient packing of
a small (12 µL, BV) device is shown in Fig. 3. The resin
completely fills the device from edge to edge, and no
extraneous beads are observed in any of the fluid-inlet
and outlet channels on either side of the device (Fig. 3).
The spherical AG50X4 resin exhibits an even, homoge-
neous packing within both the 12 µL and the 50 µL BV
devices. The smaller microfluidic structures have (35 ×
60 µm) retaining posts, whereas the larger devices require
the addition of support posts (180 × 180 µm) throughout
the column bed to ensure that the PDMS does not col-
lapse in on itself prior to packing.
[26]
The small device was
1.2 cm in length, 0.7 cm in width, and 0.011–0.012 cm in
depth, and the dimensions of the larger device were 7 cm
in length, 0.7 cm in width, and 0.011 cm in depth. The
resulting BVs are 11–12 µL and 55 µL, respectively. These
BV calculations account for the resin volume around
the loading ports, as can be seen at the top of the image
in Fig. 3, which excludes the area occupied by the internal
supporting posts in the larger microfluidic ion-exchange
column. A working BV of 50 µL was applied for consis-
tency and ease of fraction collection with these larger
devices.
Figure 1. Microfluidic ion-exchange chromatographic modules
for separating
225
Ra from its daughter isotope
225
Ac to obtain
pure
225
Ac. Each of the channel systems used in this work has
an integrated silastic medical grade tubing for a pressure con-
nection at the inlet (left end), outlet (right end), and the media
filling port between the two ends. The smaller module (top) is
1.2 cm long, 0.7 cm wide, and 0.011 cm deep, having a 11 µL
BV. The larger ion exchange module (bottom) is 7.0 cm long,
0.7 cm wide, and 0.011 cm deep with a 55 µL BV. A working BV
of 50 µL was applied for consistency and ease of fraction
collection with these devices.
SEPARATION SCIENCE AND TECHNOLOGY 3
Actinium-225 is derived from the serial alpha-decay of
233
Uto
229
Th, as well as
225
Ra, which beta-decays to
225
Ac
(Fig. 4).
10
The
225
Ra/
225
Ac used in this study was derived
from
229
Th generators established at Oak Ridge National
Laboratory (ORNL).
[11]
Based on the affinity of
225
Ra (II)
and
225
Ac (III) to commercial cation-exchange resins and
the known conditions for releasing these radionuclides in
strong acids, the processes for isotope separation were
combined with the microfluidic chromatography mod-
ules that were extensively characterized to test scalability
of this radiochemical separation.
[26]
Packed microfluidic
ion-exchange columns were stored in a humidified envir-
onment at room temperature prior to use. Immediately
before use, the resin was conditioned with 8 M nitric acid
to convert to the resin to the nitrate form. This was
followed by extensive washes with 0.1 M nitric acid.
This process also ensured the removal of potential metal
impurities from the resin, thus allowing for efficient bind-
ing of the
225
Ra/
225
Ac load mixture. To increase the utility
of this process for radiochemistry applications, the micro-
fluidic device was integrated into a semiautomated set-up
comprising a sample injector in-line with an automated
syringe pump, as well as an in-line CZT detector (Fig. 5).
This involved connecting the microfluidic ion-exchange
column to the syringe pump via manual injector and
selector ports (Fig. 5). The injector port allowed the deliv-
ery of a discrete volume of acid (50–500 µL) which is more
difficult to achieve with gravity flow. Automation allows
for a constant flow rate with minimal mixing of the
different eluent and wash phases. The eluents (1.2 M
and 8 M HNO
3
) were injected onto the resin bed through
the manual injector port, delivering exactly 500 µL
volume. For the
225
Ra/
225
Ac separation, the device was
Figure 2. The microfluidic separation module preparation process. (a) During fabrication, the channels are incorporated with medical
silastic tubing during the replicate molding stage. Fragments of tubing are reversibly glued to the master, then liquid PDMS is
poured, degassed, and cured to form the channels and retain the embedded tubing. Two devices (three tubes each) are shown prior
to cutting them off of the master wafer. (b) An electron micrograph image of an inverted section of the channels showing strainer
posts and converging channels. (c) A color image of an assembled microfluidic device loaded with red food coloring to highlight
details including the channels and strainer posts shown in subfigure B. (d) The strainer posts of the microfluidic system retain the
packed AG50X4 ion-exchange resin within the microfluidic separation column.
Figure 3. Brightfield image of a resin-packed (AG50X4 resin)
microfluidic chromatography column (12 µL BV) acquired
through an automated imaging stitching application using an
Andor iXon DU897 Ultra EMCCD camera attached to a Nikon
Eclipse Ti-E inverted microscope.
4S. DAVERN ET AL.
conditioned and loaded under gravity flow. The pump
was set up to pump water at a flow rate of 20 µL/min, and
the 500 µL injection loop was filled with 1.2 M HNO
3
and
8 M HNO
3
to elute the Ra and the Ac, respectively.
Mixtures of
225
Ra/
225
Ac in 0.1 M HNO
3
were loaded
onto the conditioned resin in the microfluidic device via
gravity flow, followed by a wash (~5 BV) with 0.1 M HNO
3
.
The selector valve was then switched to be in-line with the
fluid flow from the syringe pump, the injection loop was
loaded with 1.2 M HNO
3
and then it was switched to inject
onto the resin. After ~15 min, the injection valve was
switched to the load position, and the loop was loaded
with8MHNO
3
. Once the initial
225
Ra peak had been
collected (as observed using the in-line CZT detector)
the 8 M HNO
3
was injected onto the microcolumn to
elute the
225
Ac. The
225
Ac peak elution was monitored
using the gamma spectra for
221
Fr (218 keV),
213
Bi
(440 keV) and
225
Ac (188 keV).
The performance of the microfluidic radionuclide
separation column for one device was assessed by calculat-
ing the resolution of the
225
Ra/
225
Ac separation: R = 2
(750–450)/(250 + 150) = 1.5. Here, resolution values
between 1.0 and 1.5 and at least 98% purity have been
achieved with equal or greater than 98% peak recovery.
The resolution calculated is in general agreement with the
quantitative measures of each peak, 96.5%
225
Ac and 99.2%
225
Ra (Fig. 6). Quantitative measurement was achieved by
analyzing the elution fractions in the gamma counter as
Figure 4. Decay chart for
233
U highlighting the
225
Ra-to-
225
Ac transition by beta decay.
SEPARATION SCIENCE AND TECHNOLOGY 5
described earlier. Any uncertainty between these values
may be associated with the granularity of the time bins
(2.5 min) for the automated scintillation counter or isotope
adherencetothesidewallsoftheintegratedmodule(e.g.,
microfluidic separation module or transport tubing). The
asymmetry factor (AsF) for the column was measured as
an indication of the degree of media packing in the micro-
fluidic column, and the results (
225
Ac AsF = 1.8;
225
Ra
AsF = 1.6) indicate that the media has sufficient packing
for the separation. Excellent resolution was obtained with
reasonable reproducibility
[26]
across three individual
microfluidic platforms packed with resin (Table 1). The
separation of
225
Ac from
225
Ra here approximates the
separationachievedusingthe4mLcolumnIIIainthe
Boll et al. purification process. In two out of the three
microfluidic devices employed, the separation achieved
was on the order of >97%
225
Ra removal, with the third
microfluidic column dropping to ~79%. This may have
been the result of slight packing imperfections or differ-
ences in the amount of
225
Ra/
225
Ac loaded.
Microfluidics offer advantages amenable for
processing minute volumes with precision because they
provide for laminar flow regimes with a high degree of
control to establish stable gradients and complex mixtures
at the microliter-scale. Furthermore, microtechnology
enables the customization and integration of microscale
features that can be used to divert or mix fluids and retain
particles that can separate or combine pure substances. For
these reasons, microfluidic modules are well-suited to
enable the separation of pure substances through chemical
exchanges. Such power allows for good quality chromato-
graphic separations. As we demonstrate here, these micro-
systems can also be combined and implemented through
the automation of separation processes.
Figure 5. Schematic of automated radioisotope separation pro-
cess. Fluid infusions upstream of the microfluidic column are
controlled by gravity flow for column packing and then by
syringe pump for eluting radioisotopes under constant flow.
Two valve units connected in series between the pump and the
microfluidic chip enable access for acid media injections. The in-
line gamma detector is positioned between the microfluidic
chip and the collection vessels for monitoring and documenting
temporal changes in eluted radioactivity.
Figure 6. Elution profile of
225
Ra/
225
Ac separation achieved
using the larger microfluidic device loaded with AG50X4 resin.
A
225
Ra/
225
Ac solution containing 6.56 µCi of
225
Ra and 8.88 µCi
of
225
Ac) was loaded onto the resin. Resolution (Rs) of the peak
separation shows good peak separation; asymmetry factor
(
225
Ac, AsF = 1.8;
225
Ra, AsF = 1.6) shows that the column has
sufficient packing.
Table 1.
225
Ra/
225
Ac separations are consistent across multiple
microfluidic devices.
1.2 M HNO
3
8.0 M HNO
3
Device #
225
Ra
(%)
225
Ac
(%)
225
Ra
(%)
225
Ac
(%)
1 99.0 3.5 1.0 96.5
2 97.9 3.8 2.1 96.2
3 78.9 9.1 21.1 90.9
Average 91.9 5.5 8.1 94.5
SD 11.3 3.2 11.3 3.2
6S. DAVERN ET AL.
From our experience, the greatest limitations for con-
sidering the use of microfluidics in development and
production settings apply to the manufacture of packed
chromatography beds where the introduction of bubbles
into the packed bed is problematic. Without mastery of
media packing techniques, the introduction of bubbles
into the chromatographic bed during assemblyand opera-
tion confounds separation efficiency and resolution.
Presently the packing of chromatography media in micro-
fluidics is a manual process, however, it is one that can be
achieved without the need to work in dedicated radiation
work areas. Optimizations in design and media size
matching to minimize dead volume will also improve
separation capacity and quality. As the ability to manu-
facture plug and play microfluidics improves and systems
are developed to integrate valves into the process flow,
then readily exchangeable modules for improved radio-
isotope separations will be enabled.
Conclusion
This proof-of-concept study demonstrates the utility of
microfluidic systems for radiological separations of medi-
cally important alpha emitters such as
225
Ac. Expanding
the use of this system to more complex separations such as
the +3/+3,
225
Ac/Ln separations, and applying gradient
separations through the use of the automated syringe
pump set-up, will allow the interrogation of many more
challenging separations on the microscale. Reducing the
quantity of materials used in developing radioisotope
separations chemistry results in an associated decrease in
radiation exposure to personnel, eliminating the need for
expensive hot cells and gloveboxes. These updates should
all help to improve access to medical radioisotopes for
researchers who lack the facilities capable of handling
larger quantities of radioactive materials and further the
application of unique separations techniques for radioche-
mical separations.
Acknowledgments
Research on the development of microfluidic devices for
radioisotope separations was sponsored by the Laboratory
Directed Research and Development Program of Oak Ridge
National Laboratory, managed by UT-Battelle, LLC, for the
U. S. Department of Energy and the production of
225
Ra and
225
Ac used in these studies was supported by the DOE Office
of Nuclear Physics, Isotope Program, under contract DE-
00OR22725 with UT Battelle, LLC.
Funding
This work was supported in part by the DOE Office of
Nuclear Physics, Isotope program, and by the Laboratory
Directed Research and Development Program of Oak Ridge
National Laboratory. ORNL is managed by UT-Battelle, LLC,
for the U.S. Department of Energy under contract [DE-
00OR22725].
ORCID
Sandra Davern http://orcid.org/0000-0003-2755-8912
Larry Millet http://orcid.org/0000-0001-6443-2505
Scott Retterer http://orcid.org/0000-0001-8534-1979
Mitchel Doktycz http://orcid.org/0000-0003-4856-8343
Robert Standaert http://orcid.org/0000-0002-5684-1322
Rose Boll http://orcid.org/0000-0003-2507-4834
David DePaoli http://orcid.org/0000-0001-7172-2439
Saed Mirzadeh http://orcid.org/0000-0002-1774-7958
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