Innovative Microfluidic Chips For Investigating Intercellular Interactions

In multicellular organisms,cells worked together to perform physiological functions.Cell–cell interactions were crucial components of many biological functions,for example,cell proliferation,differentiation,and apoptosis.Microfluidic system was an excellent platform for cell research.The size of the channel was suitable for flexible manipulation of cells.The chip was transparent and had good gas permeability.In addition,microfluidics was very compatible and could be combined with a variety of technologies.Microfluidic chip has been widely used in the field of cell biology.In this paper,we proposed several chips for studying paracrine,gap junction,drug resistance,and lipid metabolism.The main contents were as follows.Cell pairing was constructed to study the interactions between cells.Hydrodynamics was used to achieve cell pairing,without external equipment.The chambers were isolated by oil to reduce cross-talk.The chip has the flexibility to adjust the ratio between cells,the distance between cells,and assemble cell patterns.Stromal cells played an important role in the metastasis of cancer cells.On this basis,the chip was used to explore the interaction of stromal cells with cancer cells at the single cell level.The results showed that endothelial cells promoted the proliferation of cancer cells.Gap junction was a direct communication between cells.A novel microchip was presented to align cells linearly,and fluorescent signals were monitored in real time.Hydrodynamics was used to non-specifically capture and immobilize single cells.Primary rat kidney fibroblast cells were used.After gap junction was formed,the fluorescent signal was transmitted between cells.In the past,to investigate gap junction,the signal was tracked on a plane.With this chip,the signal could be tracked on a line,with higher precision.Drug resistance was a problem in the cancer treatment.Drug test in vitro often lacked the discussion about cell density factor.To solve this problem,a new microchip was proposed.Different cell capture structures were designed in the chip,and the cell density gradient could be formed by adjusting the size of the capture structure.This chip was used to explore the relationship between drug resistance and cell density.Lipid metabolism of blood cell was related to the metabolic diseases.We expected to find disease markers associated with lipid metabolism in peripheral blood cells.Peripheral blood was a suspension system.The advantage of Hyperspectral SRS was label-free imaging of lipid,but imaging suspension cells was a challenge.After trying a variety of materials,agarose gel was chose.Suspension cells were fixed and arrayed with agarose gel,then intracellular lipid was detected using Hyperspectral SRS.After the cells were treated with TNF,no phenotypic differences were detected using flow cytometry,but intracellular lipids were found to be altered using Hyperspectral SRS.In this paper,based on the microfluidic platform,we proposed new methods for studying paracrine,gap junction,drug resistance,and lipid metabolism.The above new methods had advantages such as convenience,easy operation,high throughput,which were expected to facilitate related researchs.