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A beta-camera integrated with a microfluidic chip for radioassays based on real-time imaging of glycolysis in small cell populations.

ABSTRACT: An integrated ?-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.The ?-camera uses a position-sensitive avalanche photodiode to detect charged particle-emitting probes within a microfluidic chip. The integrated ?-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.The ?-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 ?-camera showed that exposure to 1 ?M PLX4032 for 3 days decreased the (18)F-FDG uptake per cell in highly sensitive M229 cells, compared with vehicle controls.The integrated ?-camera and microfluidic chip can provide digital control of live cell cultures and allow in vitro quantitative radioassays for multiple samples simultaneously.

SUBMITTER: Vu NT

PROVIDER: S-EPMC3270819 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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A beta-camera integrated with a microfluidic chip for radioassays based on real-time imaging of glycolysis in small cell populations.

Vu Nam T NT Yu Zeta T F ZT Comin-Anduix Begonya B Søndergaard Jonas N JN Silverman Robert W RW Chang Canny Y N CY Ribas Antoni A Tseng Hsian-Rong HR Chatziioannou Arion F AF

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20110501 5

<h4>Unlabelled</h4>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.<h4>Methods</h4>The β-camera uses a position-sensitive avalanche photodiode to detect c ...[more]

PMID: 21536929

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Project description:The performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by physiological barriers such as shear stress and proteins present in blood, endothelial wall, extracellular matrix, and eventually cancer cell membrane. While early disassembly will result in a premature drug release, extreme stability of the nanocarriers can lead to poor drug release and low efficiency. Therefore, comprehensive understanding of the stability and assembly state of supramolecular carriers in each stage of delivery is the key factor for the rational design of these systems. One of the main challenges is that current 2D in vitro models do not provide exhaustive information, as they fail to recapitulate the 3D tumor microenvironment. This deficiency in the 2D model complexity is the main reason for the differences observed in vivo when testing the performance of supramolecular nanocarriers. Herein, we present a real-time monitoring study of self-assembled micelles stability and extravasation, combining spectral confocal microscopy and a microfluidic cancer-on-a-chip. The combination of advanced imaging and a reliable 3D model allows tracking of micelle disassembly by following the spectral properties of the amphiphiles in space and time during the crucial steps of drug delivery. The spectrally active micelles were introduced under flow and their position and conformation continuously followed by spectral imaging during the crossing of barriers, revealing the interplay between carrier structure, micellar stability, and extravasation. Integrating the ability of the micelles to change their fluorescent properties when disassembled, spectral confocal imaging and 3D microfluidic tumor blood vessel-on-a-chip resulted in the establishment of a robust testing platform suitable for real-time imaging and evaluation of supramolecular drug delivery carrier's stability.

Dataset Information

A beta-camera integrated with a microfluidic chip for radioassays based on real-time imaging of glycolysis in small cell populations.

Publications

A beta-camera integrated with a microfluidic chip for radioassays based on real-time imaging of glycolysis in small cell populations.

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