Abstract
287
Objectives Biomolecules provide an enormous reservoir for developing specific Positron Emission Tomography (PET) imaging probes to visualize biological processes and detect biomarkers of interests in vivo. However, efficient radiolabeling of delicate biomolecules still remains challenging. As a result, biologics-based PET probe development has been greatly hampered by the high-cost screening and optimization of radiolabeling conditions using traditional bench-scale methods at the initial stage. Our idea is to create a microfluidic device capable of searching optimal radiolabeling condition with significantly reduced amount of biomolecule. The ultimate goal is to utilize our digital microfluidic platform for preparing various biologics-based, target-specific PET probes on demand, in an automated fashion with minimal operator skill.
Methods Micro-droplets, resembling an isolated, miniature batch reactor which can be composed of different reagents, allow an unprecedented degree of control over reaction conditions. A digital microfluidic chip based on a droplet generator was designed and fabricated to facilitate the microscale radiolabeling of biomolecules using a 18F-tag, N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB).
Results Consuming only small amounts of samples (200-2000 fold reduction of biomolecule), the optimal conjugation parameters were obtained rapidly by screening individual droplets with different compositions. Batches of products can be then generated in the optimal condition from one single droplet to a mouse-dose scale for probe evaluation or/and in vivo studies.
Conclusions We demonstrated the use of our digital microfluidic chip to rapidly scout conditions for [18F]SFB labeling of biomolecules. Our vision is to make PET probes easily accessible so that researchers can use them to study the underlying biology of diseases and, at the same time, clinicians can use them to gather more detailed molecular information about each individual patient before therapeutic selection or/and monitoring progress after targeted treatments.
Research Support DOE