‘Betabox’ micro molecular imaging system could spur drug trials

In vitro drug trials could get a boost from a micrometer-small molecular imaging system that captures cells and tests their response to a miniscule flood of radio-pharmaceuticals, according to a study published Aug. 26 in the Journal of Nuclear Medicine.

The tiny technology is based on a microfluidic chip called the RIMChip that is mounted directly onto the face of a beta-particle camera, which together make a “Betabox” that allows for imaging and quantitative metabolic analysis of cells in the presence of a drug.

Heading up the research team studying kinetics of the imaging system is bioengineer Jun Wang, PhD, from the NSB Cancer Center and division of chemistry and chemical engineering at California Institute of Technology in Pasadena, Calif.

The system works similarly to former in vitro 96-well plate and microchip formats, but the Betabox has perks.

“Most assay steps were similar to those of standard 96-well plate radioassays, but the Betabox assay required far fewer cells, permitted quantitation of the signal per cell, and used live cells,” wrote Wang et al.

The RIMchip is created from photolithography and elastomer molding techniques that allow the building of miniscule channels where drugs interact with a small number of cells. Each chip includes five microchannels coated in a glycoprotein called fibronectin to help cells spread and become attached to each microchannel’s four microchambers housing singular assays. Each chamber includes a waffle-structured array comprised of microwells that are 200 micrometers deep and separated by walls 30 micrometers across. The beta camera is also miniaturized and has a resolution of 600 micrometers. Breathing room of 50 micrometers separates the camera from the cell capture chamber floor.

The radiopharmaceutical is piped into the RIMchip and from there, radioassays of either suspended or adherent cells are incubated for 30 minutes and tested for the kinetics of drug response. In the case of this study, a range of cancer cell lines were tested for their response using F-18 FDG. Researchers evaluated the kinetics of response to the cancer treatments gemicitabine and erlotinib.

“We investigated the kinetics of responses of model lymphoma and glioblastoma cancer cell lines to F-18 FDG uptake after drug exposure,” the authors wrote. “Those responses were correlated with kinetic changes in the cell cycle or with changes in receptor tyrosine kinase signaling.”

Beta particle counts were normalized for each cell chamber and cell numbers to assess radiopharmaceutical uptake per cell. Results showed that the recently updated Betabox enabled an 11-fold uptick in the signal level from prior design.

Results of the radioassays revealed 8 percent variation across the RIMchip’s microchambers. T-cell assays that included 70-110 cells showed 30-fold more signal than controls.

“The Betabox platform provides a rapid screening tool for a variety of drug and cell line combinations as well as a powerful tool for mechanistic investigations.”

Interestingly, although the Betabox was able to assess uptake signal as it relates to these drugs, no cell death was found during the experiment. Further study may be needed to better understand the kinetics of different cell states.