title: A beta-camera integrated with a microfluidic chip for radioassays based on real-time imaging of glycolysis in small cell populations.
abstract: An integrated β-camera and microfluidic chip was developed that is capable of quantitative imaging of glycolysis radioassays using (18)F-FDG in small cell populations down to a single cell. This paper demonstrates that the integrated system enables digital control and quantitative measurements of glycolysis in B-Raf(V600E)-mutated melanoma cell lines in response to specific B-Raf inhibition.
  
  
  METHODS
  The β-camera uses a position-sensitive avalanche photodiode to detect charged particle-emitting probes within a microfluidic chip. The integrated β-camera and microfluidic chip system was calibrated, and the linearity was measured using 4 different melanoma cell lines (M257, M202, M233, and M229). Microfluidic radioassays were performed with cell populations ranging from hundreds of cells down to a single cell. The M229 cell line has a homozygous B-Raf(V600E) mutation and is highly sensitive to a B-Raf inhibitor, PLX4032. A microfluidic radioassay was performed over the course of 3 days to assess the cytotoxicity of PLX4032 on cellular (18)F-FDG uptake.
  
  
  RESULTS
  The β-camera is capable of imaging radioactive uptake of (18)F-FDG in microfluidic chips. (18)F-FDG uptake for a single cell was measured using a radioactivity concentration of 37 MBq/mL during the radiotracer incubation period. For in vitro cytotoxicity monitoring, the β-camera showed that exposure to 1 μM PLX4032 for 3 days decreased the (18)F-FDG uptake per cell in highly sensitive M229 cells, compared with vehicle controls.
  
  
  CONCLUSIONS
  The integrated β-camera and microfluidic chip can provide digital control of live cell cultures and allow in vitro quantitative radioassays for multiple samples simultaneously.
authors.affiliation: Crump Institute for Molecular Imaging, University of California, Los Angeles, California 90095-1770, USA.
authors.forename: Nam T
authors.initials: NT
authors.lastname: Vu
authors.forename: Zeta T F
authors.initials: ZT
authors.lastname: Yu
authors.forename: Begonya
authors.initials: B
authors.lastname: Comin-Anduix
authors.forename: Jonas N
authors.initials: JN
authors.lastname: Søndergaard
authors.forename: Robert W
authors.initials: RW
authors.lastname: Silverman
authors.forename: Canny Y N
authors.initials: CY
authors.lastname: Chang
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Hsian-Rong
authors.initials: HR
authors.lastname: Tseng
authors.forename: Arion F
authors.initials: AF
authors.lastname: Chatziioannou
mesh_terms: D001610:Beta Particles; D001692:Biological Transport / Q000187:drug effects; D002138:Calibration; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D046210:Microfluidic Analytical Techniques; D057054:Molecular Imaging / Q000295:instrumentation / Q000379:methods*; D011874:Radiometry; D059010:Single-Cell Analysis; D013449:Sulfonamides / Q000494:pharmacology; D018511:Systems Integration; D013997:Time Factors; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D000077484:Vemurafenib; D005947:Glucose