Abstract

Microfluidics have been applied to filtration of rare tumor cells from the blood as liquid biopsies. Processing is highly limited by low flow rates and device clogging due to a single function of fluidic paths. A novel method using multifunctional hybrid functional microposts was developed. A swift by-passing route for non-tumor cells was integrated to prevent very common clogging problems. Performance was characterized using microbeads (10 µm) and human cancer cells that were spiked in human blood. Design-I showed a capture efficiency of 96% for microbeads and 87% for cancer cells at 1 ml/min flow rate. An improved Design-II presented a higher capture efficiency of 100% for microbeads and 96% for cancer cells. Our method of utilizing various microfluidic functions of separation, bypass and capture has successfully guaranteed highly efficient separation of rare cells from biological fluids.

Highlights

  • Microfluidics have been applied to filtration of rare tumor cells from the blood as liquid biopsies

  • We introduce an innovative microfluidic platform with an array of uniquely designed multifunctional microposts to achieve very high capture efficiency and flow rates with the absence of detrimental clogging problems

  • Each part collaboratively contributed towards ensuring high capture efficiency while overcoming the generic problems of low flow rates and clogging in existing microfluidic technologies

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Summary

Introduction

Microfluidics have been applied to filtration of rare tumor cells from the blood as liquid biopsies. An unmet need in particle-based biomedical research is efficient capture and retrieval of viable cells for downstream liquid biopsy investigations (e.g., drug sensitivity testing of rare circulating tumor cells (CTCs) from cancer patients’ blood), while maintaining a high flow rate and clog-free device f­eatures[4]. Many microfluidic techniques that incorporate size-based enrichment (such as membrane ­microfiltration[7], pinched flow ­fractionation[8], deterministic lateral d­ isplacement[9], and h­ ydrophoresis10) have the potential for a wide range of applications in biomedicine Another major challenge is to efficiently capture rare cells in a viable state from various media like aerosols, blood, or other body fluids. Most of the studies conducted using microfluidic devices have revealed the need for very low flow rates (< 0.05 ml/min) to maintain an acceptable level of capture efficiency, these lead to prolonged and Scientific Reports | (2021) 11:16685

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