Concentration Match Based Modulation for Clogging-Free Filtration Through Micropore Arrays

Liquid biopsy techniques for the rare tumor cell separation from various body fluids have shown enormous promise in cancer detection and prognosis monitoring. High throughput is a critical index in practical application for the liquid biopsy of a large-volume (>10 mL) clinical sample. The micropore array based filtration has been well known as the most promising technique to realize a high throughput at mL/min level, along with a high recovery rate of rare cells. However, restricted by the filtration area and density of micropore number, clogging often happens in the operation of practical clinical samples with complicated components, and thus results in a failure of the specific target separation. Therefore, an effective strategy to solve the clogging problem is urgent in the micropore array filtration based liquid biopsy. This paper proposes a concentration match based modulation mechanism for the first time, and develops a dilution aiding method to solve the clogging problem in the micropore array filtration. Theoretical analysis and experimental verifications demonstrate this strategy could simply and reliably fulfill a clogging-free filtration and thus a high-efficiency separation of different targets from complicated clinical samples. This strategy will be widely applicable as a common and key technology to guide clinical sample pretreatments and device designs in the micropore array filtration based liquid biopsy.