Optical Tracing Of Intracellular Drugs On Microfluidic Chips

As human pay more attention to personal health,the demand for fast,portable and comprehensive medical treatment becomes more and more urgent.In recent years,the development of the microfluidic platform in the field of biological analysis has begun to miniaturize and integrate cellular drug assays.Surface-Enhanced Raman Scattering(SERS)has attracted more attention due to the advantages of non-organizational damage,high sensitivity and in-situ real-time detection.The combination of microfluidic and SERS technology not only satisfies the need of high throughput intracellular detection,but also provides a bionic,controllable detection platform for drug analysis.In this paper,the microfluidic platform is designed for multiple synchronization detection and in vitro tissue simulation.And the optical tracing technology of biomolecule is realized by using label-free SERS and Raman-label SERS.First,a microfluidic chip has been fabricated to perform simultaneous pharmacokinetic analysis of multiple drugs.Using controllable pneumatic valve that made by dual-layer PDMS chip,independent culture of He La and SKBR3 cells can be achieved.Besides,simultaneous characterization of intracellular 6MP and MMI can also be performed using SERS signals.In addition,the analysis of the distribution,absorption,and metabolism of 6MP and MMI was accomplished using intracellular silver substrate.The label-free SERS technology can also provide fingerprints to monitor the structural changes of intracellular drugs.Taking the platform as a simplified model,expanding the scale of the chip and testing type,there is an opportunity to achieve high throughput cellular drug analysis in future.Besides,we demonstrate a combined microfluidic platform that can be used for three-dimensional culture of vascular endothelial cells as well as the optical monitoring of paracrine activity.The platform consists of two parts: a 3D culture chip and a quantitative detection chip.The 3D culture chip has two hydrogel channels for 3D co-culture and two fluid channels as an arterial/venous.Endothelial cells(HUVECs)can be co-cultured with fibroblasts or breast cancer cells,respectively,to mimic the microenvironment of tumor angiogenesis in vivo.Vascular endothelial growth factor(VEGF),secreted by cell-cell or cell-matrix interactions,can be captured by the quantitative detection chip and enables highly sensitive SERS characterization.Au@Ag NRs embedded with DTNB are prepared as SERS probes with a detection limit of 1 pg/m L.The results show that fibroblasts and tumor cells play different roles in angiogenesis and stimulate the VEGF secretion of different concentrations.Moreover,the vascular morphology and VEGF content in the platform can respond to activators and inhibitors respectively.Therefore,the microfluidic platform combined with SERS technology has great potencial in tissue analysis and in vitro tumor therapy.