scholarly journals Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2 from solid Ni targets

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Johan Svedjehed ◽  
Christopher J. Kutyreff ◽  
Jonathan W. Engle ◽  
Katherine Gagnon
Keyword(s):  
High Purity ◽  
Radiochemical Yield ◽  
Proof Of Concept ◽  
Automated Method ◽  
Production Run ◽  
Separation Factors ◽  
Single Use ◽  
Target Production ◽  
Dissolution Efficiency ◽  
Hcl Concentration

Abstract Background A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics, and generally lengthy separation chemistries for 64Cu/64Ni, upon which 61Cu chemistry is often based. Methods A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [61Cu]CuCl2, removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions. Results 61Cu saturation yields of 190 ± 33 MBq/μA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4% with an average radiochemical yield of 90.4 ± 3.2% (N = 5). The isolated activity was collected approximately 65 min post end of bombardment in ~ 2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10− 5% vs. 61Cu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 106, EoB molar activities 85 ± 23 GBq/μmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively. Conclusion High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.

scholarly journals Automated, cassette-based isolation and formulation of high-purity [61Cu]CuCl2 from solid Ni targets

2020 ◽  
Author(s):  
Johan Svedjehed ◽  
Christopher J Kutyreff ◽  
Jonathan W Engle ◽  
Katherine Gagnon
Keyword(s):  
High Purity ◽  
Radiochemical Yield ◽  
Proof Of Concept ◽  
Automated Method ◽  
Production Run ◽  
Separation Factors ◽  
Single Use ◽  
Target Production ◽  
Dissolution Efficiency ◽  
Hcl Concentration

Abstract Background: A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics and generally lengthy separation chemistries for 64Cu/64Ni, upon which 61Cu chemistry is often based. Methods: A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [61Cu]CuCl2, removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions. Results: 61Cu saturation yields of 190 ± 33 MBq/µA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4 % with an average radiochemical yield of 90.4 ± 3.2 % (N = 5). The isolated activity was collected approximately 65 minutes post end of bombardment in ~2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10-5 % vs. 61Cu by activity, Ni separation factors ≥ (2.2 ± 1.8) × 106, EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively. Conclusion: High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.

scholarly journals Automated, Cassette-Based Isolation and Formulation of High-Purity [61Cu]CuCl2 from Solid Ni Targets

2020 ◽  
Author(s):  
Johan Pettersson ◽  
Christopher J Kutyreff ◽  
Jonathan W Engle ◽  
Katherine Gagnon
Keyword(s):  
High Purity ◽  
Radiochemical Yield ◽  
Proof Of Concept ◽  
Automated Method ◽  
Production Run ◽  
Separation Factors ◽  
Single Use ◽  
Target Production ◽  
Dissolution Efficiency ◽  
Hcl Concentration

Abstract Background: A need for improved, cassette-based automation of 61Cu separation from irradiated Ni targets was identified given the growing interest in theranostics and generally lengthy separation chemistries for 64Cu/ 64Ni, upon which 61Cu chemistry is often based.Methods: A method for separating 61Cu from irradiated natNi targets was therefore developed, with provision for target recycling. Following deuteron irradiation, electroplated natNi targets were remotely transferred from the cyclotron and dissolved in acid. The dissolved target solution was then transferred to an automated FASTlab chemistry module, where sequential TBP and TK201 (Triskem) resins isolated the [ 61Cu]CuCl2 , removed Ni, Co, and Fe, and concentrated the product into a formulation suitable for anticipated radiolabelling reactions.Results: 61Cu saturation yields of 190 ± 33 MBq/µA from energetically thick natNi targets were measured. The average, decay-corrected, activity-based dissolution efficiency was 97.5 ± 1.4 % with an average radiochemical yield of 90.4 ± 3.2 % (N = 5). The isolated activity was collected approximately 65 minutes post end of bombardment in ~2 mL of 0.06 M HCl (HCl concentration was verified by titration). Quality control of the isolated [61Cu]CuCl 2 (N = 5) measured 58Co content of (8.3 ± 0.6) × 10-5 % vs. 61Cu by activity, Ni separation factors ≥(2.2 ± 1.8) × 106 , EoB molar activities 85 ± 23 GBq/µmol and NOTA-based EoB apparent molar activities of 31 ± 8 MBq/nmol and 201 MBq/nmol for the 30 min and 3.3 h (N = 1) irradiations, respectively.Conclusion: High purity 61Cu was produced with the developed automated method using a single-use, cassette-based approach. It was also applicable for 64Cu, as demonstrated with a single proof-of-concept 64Ni target production run.

scholarly journals Microdroplet-based system for culturing of environmental microorganisms using FNAP-sort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kanako Saito ◽  
Yuri Ota ◽  
Dieter M. Tourlousse ◽  
Satoko Matsukura ◽  
Hirotsugu Fujitani ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
High Purity ◽  
Droplet Microfluidics ◽  
Individual Growth ◽  
Proof Of Concept ◽  
Widespread Adoption ◽  
Technical Challenges ◽  
On Chip ◽  
Uncultured Microorganisms ◽  
Environmental Microbes

AbstractDroplet microfluidics has emerged as a powerful technology for improving the culturing efficiency of environmental microorganisms. However, its widespread adoption has been limited due to considerable technical challenges, especially related to identification and manipulation of individual growth-positive droplets. Here, we combined microfluidic droplet technology with on-chip “fluorescent nucleic acid probe in droplets for bacterial sorting” (FNAP-sort) for recovery of growth-positive droplets and droplet microdispensing to establish an end-to-end workflow for isolation and culturing of environmental microbes. As a proof-of-concept, we demonstrate the ability of our technique to yield high-purity cultures of rare microorganisms from a representative complex environmental microbiome. As our system employs off-the-shelf commercially available equipment, we believe that it can be readily adopted by others and may thus find widespread use toward culturing the high proportion of as-of-yet uncultured microorganisms in different biomes.

scholarly journals Smart Pooling: AI-Powered COVID-19 Informative Group Testing

2021 ◽  
Author(s):  
Maria Escobar ◽  
Guillaume Jeanneret ◽  
Laura Bravo-Sánchez ◽  
Angela Castillo ◽  
Catalina Gómez ◽  
...  
Keyword(s):  
Machine Learning ◽  
False Negative ◽  
Group Testing ◽  
Error Rates ◽  
Molecular Testing ◽  
Proof Of Concept ◽  
Efficiency Gains ◽  
Automated Method ◽  
Sociodemographic Data ◽  
False Negative Error

Abstract Massive molecular testing for COVID-19 has been pointed out as fundamental to moderate the spread of the pandemic. Pooling methods can enhance testing efficiency, but they are viable only at low incidences of the disease. We propose Smart Pooling, a machine learning method that uses clinical and sociodemographic data from patients to increase the efficiency of informed Dorfman testing for COVID-19 by arranging samples into all-negative pools. To do this, we ran an automated method to train numerous machine learning models on a retrospective dataset from more than 8,000 patients tested for SARS-CoV-2 from April to July 2020 in Bogotá, Colombia. We estimated the efficiency gains of using the predictor to support Dorfman testing by simulating the outcome of tests. We also computed the attainable efficiency gains of non-adaptive pooling schemes mathematically. Moreover, we measured the false-negative error rates in detecting the ORF1ab and N genes of the virus in RT-qPCR dilutions. Finally, we presented the efficiency gains of using our proposed pooling scheme on proof-of-concept pooled tests. We believe Smart Pooling will be efficient for optimizing massive testing of SARS-CoV-2.

scholarly journals Automated Light-Induced Synthesis of 89Zr-Radiolabeled Antibodies for Immuno-Positron Emission Tomography

2021 ◽  
Author(s):  
Simon Klingler ◽  
Jason Holland
Keyword(s):  
Positron Emission Tomography ◽  
Nuclear Medicine ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Desferrioxamine B ◽  
Automated Method ◽  
Isolation And Characterization ◽  
Positron Emission ◽  
The Many ◽  
Radiolabeled Antibodies

Abstract Clinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography (PET) imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in <25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our Good Laboratory Practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in <25 min with an overall decay-corrected radiochemical yield of 20.1±2.4% (n=3), a radiochemical purity >99%, and chemical purity >99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

Improving Network Management by XML to Relational Data Translation

2013 ◽  
Vol 5 (3) ◽  
pp. 34-48
Author(s):  
Mahabubul Alam ◽  
Salam Salloum ◽  
Mohammad Husain
Keyword(s):  
Network Management ◽  
Wireless Network ◽  
Information Needs ◽  
Relational Databases ◽  
Proof Of Concept ◽  
Process Data ◽  
Automated Method ◽  
Extensible Markup ◽  
Data Translation ◽  
Logging Tool

Network management is a critical component in both wired and wireless network. In wireless networks, the network dynamics changes rapidly and the network management information needs to be updated frequently. Due to its structured form and ease of usage in communication, eXtensible Markup Language (XML) is preferred as a configuration and logging tool in network management. However, it is convenient to use relational databases such as SQL to store and process data of wireless network management where frequent updates are necessary. In this paper, the authors show an automated method of converting XML documents to store in relational. We have implemented a proof of concept and compared performance to existing approach.

Expansion of Adipose Derived Stromal Cells from Stromal Vascular Fraction in a Single-Use Bioreactor: Proof of Concept in the Mobius® 3L

Cytotherapy ◽  
2016 ◽  
Vol 18 (6) ◽  
pp. S138
Author(s):  
M. Gadelorge ◽  
M. Bourdens ◽  
C. Bardiaux ◽  
N. Espagnolle ◽  
J. Murrell ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Stromal Vascular Fraction ◽  
Proof Of Concept ◽  
Adipose Derived Stromal Cells ◽  
Single Use

scholarly journals Design, prototyping, and evaluation of a collapsible device for single-operator sheathing of ultrasound probes

2014 ◽  
Vol 5 (1) ◽  
pp. 7-13
Author(s):  
S. A. Lopez ◽  
L. R. Hernley ◽  
E. N. Bearrick ◽  
L. M. Tanenbaum ◽  
M. A. C. Thomas ◽  
...  
Keyword(s):  
Interventional Ultrasound ◽  
Proof Of Concept ◽  
Ultrasound Guided ◽  
Single Operator ◽  
Single Use ◽  
Single User ◽  
Probe Holder ◽  
Ultrasound Probes

Abstract. During interventional ultrasound-guided procedures, sterility is maintained by covering the transducer head and cord with a sterile sheath. The current sheathing technique is cumbersome, requires an assistant to complete, and poses a risk of tangling the probe cord and breaching the sterile barrier. This paper presents the design, proof-of-concept prototyping, and evaluation of a probe holder and cartridge-style, single-use applicator that enables faster, more reliable, single-user sheathing of ultrasound probes, with a decreased risk of compromising sterility.

Multi-chamber single-use bioreactor– A proof of concept prototype

2018 ◽  
Vol 130 ◽  
pp. 113-120 ◽  
Author(s):  
Momen Amer ◽  
Joshua D. Ramsey
Keyword(s):  
Proof Of Concept ◽  
Single Use

scholarly journals Automated light-induced synthesis of 89Zr-radiolabeled antibodies for immuno-positron emission tomography

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon Klingler ◽  
Jason P. Holland
Keyword(s):  
Positron Emission Tomography ◽  
Nuclear Medicine ◽  
Positron Emission Tomography Imaging ◽  
Radiochemical Yield ◽  
Emission Tomography ◽  
Desferrioxamine B ◽  
Automated Method ◽  
Isolation And Characterization ◽  
Positron Emission ◽  
Radiolabeled Antibodies

AbstractClinical production of 89Zr-radiolabeled antibodies (89Zr-mAbs) for positron emission tomography imaging relies on the pre-conjugation of desferrioxamine B (DFO) to the purified protein, followed by isolation and characterization of the functionalized intermediate, and then manual radiosynthesis. Although highly successful, this route exposes radiochemists to a potentially large radiation dose and entails several technological and economic hurdles that limit access of 89Zr-mAbs to just a specialist few Nuclear Medicine facilities worldwide. Here, we introduce a fully automated synthesis box that can produce individual doses of 89Zr-mAbs formulated in sterile solution in < 25 min starting from [89Zr(C2O4)4]4– (89Zr-oxalate), our good laboratory practice-compliant photoactivatable desferrioxamine-based chelate (DFO-PEG3-ArN3), and clinical-grade antibodies without the need for pre-purification of protein. The automated steps include neutralization of the 89Zr-oxalate stock, chelate radiolabeling, and light-induced protein conjugation, followed by 89Zr-mAb purification, formulation, and sterile filtration. As proof-of-principle, 89ZrDFO-PEG3-azepin-trastuzumab was synthesized directly from Herceptin in < 25 min with an overall decay-corrected radiochemical yield of 20.1 ± 2.4% (n = 3), a radiochemical purity > 99%, and chemical purity > 99%. The synthesis unit can also produce 89Zr-mAbs via the conventional radiolabeling routes from pre-functionalized DFO-mAbs that are currently used in the clinic. This automated method will improve access to state-of-the-art 89Zr-mAbs at the many Nuclear Medicine and research institutions that require automated devices for radiotracer production.

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