Cerenkov Imaging of Microfluidic Chips

Overview

The standard analytical tools of the radiochemistry lab, namely the dose calibrator, radio-HPLC, and radio-TLC, do not permit detailed study of what goes on inside microfluidic chips that handle radiolabeled compounds (e.g. synthesizer chips, assay chips, etc.).

Radio-TLC and radio-HPLC can only analyze the composition of radioactive species in liquids that can be removed from the chip. While this gives insights into the progress of radiochemical reactions, if radiolabeled substances are absorbed or adsorbed by the chip materials, they are not reflected in the chromatogram, and so it is necessary to be careful in the interpretation of the data. Furthermore, because the volume of microfluidic chips is so tiny, performing radio-TLC or radio-HPLC consumes a large portion of the liquid on the chip and often is an end-point measurement only.

Similarly, a dose calibrator measures only the total radioactivity in the whole chip at the time of measurement. In rare cases, if the chip can be disassembled during or after an experiment, the dose calibrator can also measure the radioactivity in different portions of the chip. Generally, however, it is not possible to track the amount of radioactivity in a specific part of a chip over time.

To solve these challenges, Dr. Arion Chatziioannou's group in the Crump Institute for Molecular Imaging at UCLA has developed a "radioactivity camera" based on the detection of Cerenkov radiation emitted by high-energy positrons travelling through nearby transparent materials such as solvent and the materials from which the microfluidic chip is made (see Figure 1). Together we have been developing the system for in situ monitoring of processes involving radioisotopes (e.g., radiochemical synthesis) in microfluidic chips. This system is capable of near real-time imaging inside the chip at multiple time points, and can quantitate the amount of radioactivity in a selected region of interest (ROI) in the image for a variety of studies.

Results

Using Cerenkov imaging, we have studied various aspects of the radiosynthesis of 2-[F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG) in poly(dimethylsiloxane) (PDMS) microfluidic chips, and also the synthesis of several F-18-labeled compounds in electrowetting-on-dielectric (EWOD) microfluidic chips.

Figure 1: (A) Cerenkov radiation (faint blue light) is produced when energetic particles travel through a medium faster than the speed of light in that medium. This image shows the reactor core of the Advanced Test Reactor (Source). (B) Cerenkov radiation is emitted as positrons decay within a microfluidic chip. (C) Photograph of a PDMS microfluidic chip. (D) Cerenkov image of the same chip when filled with radioactive solution.

Current Status / Next Steps

The systems are in routine use in the laboratory for troubleshooting and optimization of microfluidic radiochemistry projects.

Related Publications

J. S. Cho, R. Taschereau, S. Olma, K. Liu, Y.-C. Chen, C. K.-F. Shen, R. M. van Dam, and A. F. Chatziioannou, “Cerenkov radiation imaging as a method for quantitative measurements of beta particles in a microfluidic chip,” Physics in Medicine and Biology, vol. 54, no. 22, pp. 6757–6771, 2009. (PDF Link)
W.-Y. Tseng, J. S. Cho, X. Ma, A. Kunihiro, A. Chatziioannou, and R. M. van Dam, “Toward reliable synthesis of radiotracers for positron emission tomography in PDMS microfluidic chips: Study and optimization of the [18F] fluoride drying process,” in Technical Proceedings of the 2010 NSTI Nanotechnology Conference and Trade Show, Anaheim, CA, 2010, vol. 2, pp. 472–475. (PDF Link)
P. Y. Keng, S. Chen, H. Ding, S. Sadeghi, G. J. Shah, A. Dooraghi, M. E. Phelps, N. Satyamurthy, A. F. Chatziioannou, C.-J. Kim, and R. M. van Dam, “Micro-chemical synthesis of molecular probes on an electronic microfluidic device,” PNAS, vol. 109, no. 3, pp. 690–695, 2012. (PDF Link)
A. A. Dooraghi, P. Y. Keng, S. Chen, M. R. Javed, C.-J. “CJ” Kim, A. F. Chatziioannou, and R. M. van Dam, “Optimization of microfluidic PET tracer synthesis with Cerenkov imaging,” Analyst, vol. 138, no. 19, pp. 5654–5664, Aug. 2013. (PMC Link)

Team Members and Collaborators

Former:

Jennifer Cho (graduate student from Chatziioannou lab)
Nam Vu (graduate student from Chatziioannou lab)
Wei-Yu Tseng (postdoctoral scholar)
Xiaoxiao Ma (graduate student)
Andrew Kunihiro (undergraduate student)
Kabir Mahal (undergraduate student)
Prof. Arion Chatziioannou (collaborator)
Prof. Pei Yuin Keng (postdoctoral scholar; then collaborator)
Alex Dooraghi (graduate student then postdoctoral scholar from Chatziioannou lab)

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