Herringbone Microfluidic Probe for Multiplexed Affinity‐Capture of Prostate Circulating Tumor Cells

Abstract

In this work, for first time, circulating tumor cells (CTCs) are captured on an open biofunctionalized substrate with multiplexing capability. This is achieved by developing a new microfluidic probe (MFP) integrated with radially staggered herringbone (HB) elements for microvortex generation. The new tool, named as herringbone microfluidic probe (HB‐MFP), is a channel‐less microfluidic system with physically separated bottom capture substrate and top fluidics delivery system. The concept allows for functionalizing the capture substrate with multiple biorecognition ligands (in this work, stripes of different capture antibodies) and scanning the fluidics delivery system across the substrate in a 2D printing‐like movement. Using the HB‐MFP, CTCs are efficiently captured from prostate cancer blood samples through their specific EpCAM, PSMA, and PSA antigens in a single run, with counts ranging from as low as 6 CTCs mL‐1 (localized cancer patients) to as high as 280 CTCs mL‐1 (metastatic cancer patients). In the process, CTC clusters with sizes of as high as 40–50 cells are also successfully captured. The results indicate that multiplex profiles of CTCs could reveal certain cellular phenotypes based on PSMA and PSA expression levels. The developed HB‐MFP is simple and robust to use, allows for high throughput sample processing, and provides seamless access to captured CTCs for further downstream characterization.

Biomedical Applications of Microfluidic Devices: A Review

“…For curved channels, in addition to induced lift forces, due to the centrifugal force, a drag force is exerted on particles by the formation of a secondary flow called the Dean flow, which is perpendicular to the primary flow. Aside from curved microchannels, other secondary flow generating geometries including spiral channels [ 37 ], serpentine channels [ 1 ], successive contraction and extraction channels [ 3 , 38 ], top surface slanted grooves [ 5 , 39 ], and herringbones structures [ 40 ] have been studied for particle sorting. The inherent high volumetric flow rates in inertial microfluidic devices make it favorable for cell separation [ 41 ].…”

The Crucial Roles of Bmi-1 in Cancer: Implications in Pathogenesis, Metastasis, Drug Resistance, and Targeted Therapies

“…It is related to the clinical stage, pathological classification, and lymph node metastasis, and can be used as one of the predictors for prognosis and recurrence in tumor patients. With the development of molecular biological technology and the application of gene chip technology, development is expected of a microfluidic multi-indicator joint inspection chip, a circulating cancer-cell capture chip, and other devices for automatic detection of Bmi-1 expression [ 208 , 209 , 210 ]. In addition, Bmi-1 is involved in the occurrence and development of many tumors, and the targeted therapy of cancer stem cells is an important measure for future development.…”

Characterizing circulating tumor cells using affinity-based microfluidic capture and AFM-based biomechanics

“…Some of the AFM-Chip limitations can be overcome, for example by employing 3D printing for cost- and time-effective master mold fabrication, fabricating larger channels for increased throughput, and exposing blood to longer capture path by sequentially connecting three AFM-Chips. Recently, on the other hand, we proposed more effective way of multiplex capturing CTCs from whole blood samples of cancer patients by introducing the HB-MFP ( Glia et al., 2021 ). The HB-MFP, which is acronym for herringbone-microfluidic probe, is a fully 3D printed “open microfluidic” device, that allows for multiplex capture of CTCs in a single run, high throughput by processing larger blood volumes for higher CTC capture, complete cell recovery by minimizing cell loses and damage, and seamless external access to captured cells.…”