Non-Confidential Description
INTRO SENTENCE: UCLA researchers in the Departments of Bioengineering and Medical and Molecular Pharmacology have developed a novel high throughput microscale radiosynthesizer capable of optimizing radiolabeling of bioactive molecules for the purpose of cancer imaging or drug development.
TITLE: High-throughput Radiochemistry System
BACKGROUND: The use of radioactive nuclides for the tracing of biological pathways dates to the early 1900s, where researchers utilized radioactive iodine to stage thyroid cancer. Over the past century, radiochemical methodologies have incorporated a vast selection of radioactive nuclides, that can in different mechanisms traces small molecule, peptide, and antibody traffic in the body. The use of specialized gamma cameras leads to empirical images that show regions of uptake of these radiolabeled chemical species. These strategies have led to clinically viable imaging candidates that can more effectively stage cancer development through the body and direct a more personalized strategy to its treatment. However, radionuclide labeling has recently found much interest in drug development in large pharmaceutical companies. The tracing of radiolabeled drug candidates explains the metabolic clearances that drugs face and can also be used to tell if a drug has on target effectiveness. There is however, a current and significant limitation to the widespread use of radiolabeling bioactive analogues, that lies in the synthetic optimization. Typical radiochemical synthesizing systems can only label one substrate in a single session. Should the initial attempt fail, multiple optimization sessions could be needed to produce a viable radiolabeled candidate for imaging biodistribution. Therefore, there is a current unmet need in the field of radiochemistry to develop a radiosynthesizing module that is capable of multiple synthetic labeling attempts in a single session.
INNOVATION: UCLA researchers in the Departments of Bioengineering and Medical and Molecular Pharmacology have developed a novel high throughput microscale radiosynthesizer capable of optimizing radiolabeling of bioactive molecules for the purpose of cancer imaging or drug development. This automated radiosynthesizing system, utilizes flat silicon wafers with 16 site directed spots for reactions, with a set of four separate heating systems. Separation of these silicon wafer reactors allow for optimization in reaction: temperature, solvent, precursor concentration, and time. The automated radiosynthesizer utilizes microliter sized droplets for reaction volumes, limiting precursor and solvent consumption. Due to the disposable nature of the silicon reactor wafers, many new conditions could be attempted by replacement. This invention therefore solves a currently unmet need for optimization of radiochemical reactions and could be applied to cancer imaging or novel pharmaceutical development.
POTENTIAL APPLICATIONS:
• Use as a reusable radiochemical synthesizer for multiple reaction optimizations per session
• The development of a chemical library of radiolabelable bioactive small molecules; novel PET tumor imaging agent discovery
• The labeling of drug candidates for screening potentially poor metabolically stable molecules
ADVANTAGES:
• The use of microliter sized droplets, allows minimal consumption of reagents for the optimization of reactions
• The use of disposable reactor vessels (silicon wafers), leads to a fast way to reuse the synthesizer system with little downtime; it also lessens the chance for radiation worker exposure comparative to a cleaning procedure
• Fully automated system that lowers radiation exposure chances
DEVELOPMENT-TO-DATE: The 16 spot silicon wafer chips have been tested manually, but the automated robot handling system is currently in development.
Related Papers (from the inventors only):
Alejandra Rios, Jia Wang, Philip H. Chao, R. Michael van Dam. A novel multi-reaction microdroplet platform for rapid radiochemistry optimization. RSC Advances 9: 20370-20374, 2019. DOI: 10.1039/C9RA03639C.
Jia Wang, Philip H. Chao, R. Michael van Dam. Ultra-compact, automated microdroplet radiosynthesizer. Lab on a Chip 19: 2415 - 2424, 2019. DOI: 10.1039/C9LC00438F.
Lead Inventor: R. Michael van Dam
OTT/iBridge Category Keywords [link]:
Engineering > Robotics and Automation
TDG Keywords:
Physical Sciences > Mechanical Systems > Robotics, Engines, Turbines, Aerospace, MEM’s
Technology-related keywords (search terms, be liberal): Radiochemistry, Microfluidics, Radiosynthesizer, Robotics, Silicon Wafer, High throughput Synthesizer, Cancer Imaging, Drug Development, PET