Construction And Application Of Parallel High Throughput Cell Mechanical Phenotyping Instrument Based On Magnetic Field

Malignant cancer cells and normal cells are different in many aspects,such as gene expression and metabolite composition.Studies of these distinguishing characteristics provide insight into mechanisms of cancer development and the identification of tumor markers that can be detected by various immunological,biological and chemical methods for diagnostic applications.Recently,significant differences in the mechanical properties of malignant cancer cells and normal cells have been observed,suggesting that this integrative property might also be exploited for mechanistic and diagnostic investigations.However this characterization requires a large amount of data and consequent extensive statistical analysis,and conventional measurements are slow and examine only a few cells at a time,thus limiting its potential application as a tumor marker.To overcome this problem,we have designed and engineered a parallel high throughput cell mechanical phenotyping instrument based on magnetic tweezers.In particular,using a design similar to that of a single-pole piece electromagnetic lens and applying a novel mechanism to identify the spatial position of magnetic beads,we are able to apply a uniform force of up to 40 p N to micron-sized magnetic beads within a region of 1mm diameter.Using an automated stage,we can measure the mechanical properties of more than 1000 cells within a half hour,readily satisfying the high-throughput demand for routine cell mechanical phenotyping.We have applied this instrument to characterize the mechanical properties of a colon cancer cell line,finding,for the first time,that the epithelial–mesenchymal transition is associated with a significant change in cell elasticity,with the more malignant mesenchymal phenotype unexpectedly markedly stiffer.We anticipate that this device will find broad use in the identification and characterization of the mechanical phenotype of cells,both healthy and diseased,thereby establishing this property as a powerful indicator of cellular state.