A mini-panel PET scanner-based microfluidic radiobioassay system allowing high-throughput imaging of real-time cellular pharmacokinetics†
On-chip radiometric detection of biological samples using radiotracers has become an emerging research field known as microfluidic radiobioassays. Performing parallel radiobioassays is highly desirable for saving time/effort, reducing experimental variation between assays, and minimizing the cost of the radioisotope. Continuously infused microfluidic radioassay (CIMR) is one of the useful tools for investigating cellular pharmacokinetics and assessing the binding and uptakes of radiopharmaceuticals. However, existing CIMR systems can only measure the dynamics of one sample at a time due to the limited field of view (FOV) of the positron detector. To increase the throughput, we propose a new CIMR system with a custom-built miniaturized panel-based positron-emission tomography (PET) scanner and a parallel infusion setup/method, capable of imaging the cellular pharmacokinetics of three samples in one measurement. With this system, the pharmacokinetics of parallel or comparison samples can be imaged simultaneously. The increased throughput is attributed to two innovations: 1) the large 3D FOV of the mini-panel PET scanner, enabling more samples to be imaged in the microfluidic chip; and 2) a parallel infusion method, in which only one reference chamber is needed for indicating the dynamic input of the infused radiotracer medium, thus saving the total reference chambers needed compared to the current sequential infusion method. Combining the CIMR technique and the mini-panel PET scanner, this study also firstly demonstrated the feasibility of using PET, as an imaging modality, for microfluidic radiobioassays. Besides the increased throughput, the 3D imaging of PET also provides possibilities for further applications such as organoid/3D culturing systems, non-planar microfluidics, and organs-on-chips. The system is more practical for a broader range of applications in nuclear medicine, molecular imaging, and lab-on-a-chip studies.