Abstract

Large-area micropore arrays with a high porosity are in high demand because of their promising potential in liquid biopsy with a large volume of clinical sample. However, a micropore array with a large area and a high porosity faces a serious mechanical strength challenge. The filtration membrane may undergo large deformation at a high filtration throughput, which will decrease its size separation accuracy. In this work, a keyhole-free Parylene molding process has been developed to prepare a large (>20 mm × 20 mm) filtration membrane containing a 2.5-dimensional (2.5D) micropore array with an ultra-high porosity (up to 91.37% with designed pore diameter/space of 100 μm/4 μm). The notation 2.5D indicates that the large area and the relatively small thickness (approximately 10 μm) of the fabricated membranes represent 2D properties, while the large thickness-to-width ratio (10 μm/ < 4 μm) of the spaces between the adjacent pores corresponds to a local 3D feature. The large area and high porosity of the micropore array achieved filtration with a throughput up to 180 mL/min (PBS solution) simply driven by gravity. Meanwhile, the high mechanical strength, benefiting from the 2.5D structure of the micropore array, ensured a negligible pore size variation during the high-throughput filtration, thereby enabling high size resolution separation, which was proven by single-layer and multi-layer filtrations for particle separation. Furthermore, as a preliminary demonstration, the prepared 2.5-dimensional Parylene C micropore array was implemented as an efficient filter for rare cancer cell separation from a large volume, approximately 10 cells in 10 mL PBS and undiluted urine, with high recovery rates of 87 ± 13% and 56 ± 13%, respectively.

Highlights

  • 21 Ni microcavity array26 3D Parylene C micropore 9 μm (top membrane) μm (top membrane) 1 cm[2] arrays (double-layer) 8 μm (bottom membrane) μm (bottom membrane)

  • The successful separation of rare cancer cells from a clinical sample is extremely important for liquid biopsies in precision medicine[1,2,3,4,5,6,7,8,9,10,11]

  • The SEM image of the cross-sectional view of the Parylene C microstructure depicted in Fig. 3a4 exhibits a concave surface after keyhole removal during the annealing treatment of the modified molding process performed after reactive ion etching (RIE)

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Summary

21 Ni microcavity array

26 3D Parylene C micropore 9 μm (top membrane) μm (top membrane) 1 cm[2] arrays (double-layer) 8 μm (bottom membrane) μm (bottom membrane). Owing to the fabrication difficulties and mechanical limitations, the previously reported micropore-array filtration structures[15,16,17,18,19,20,21,22,24,25,26,27,28] usually had a relatively large supporting space (edge-to-edge distance) between the adjacent micropores and thereby had a low porosity (the maximum reported was 18%24), which led to a limited, high enough for CTC-based liquid biopsy, filtration throughput (

Materials and methods
23 À 9μ 252ð1 À μÞ
Results and discussion
Conclusions
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