Abstract

Worldwide, prostate cancer sits only behind lung cancer as the most commonly diagnosed form of the disease in men. Even the best diagnostic standards lack precision, presenting issues with false positives and unneeded surgical intervention for patients. This lack of clear cut early diagnostic tools is a significant problem. We present a microfluidic platform, the Time-Resolved Hydrodynamic Stretcher (TR-HS), which allows the investigation of the dynamic mechanical response of thousands of cells per second to a non-destructive stress. The TR-HS integrates high-speed imaging and computer vision to automatically detect and track single cells suspended in a fluid and enables cell classification based on their mechanical properties. We demonstrate the discrimination of healthy and cancerous prostate cell lines based on the whole-cell, time-resolved mechanical response to a hydrodynamic load. Additionally, we implement a finite element method (FEM) model to characterise the forces responsible for the cell deformation in our device. Finally, we report the classification of the two different cell groups based on their time-resolved roundness using a decision tree classifier. This approach introduces a modality for high-throughput assessments of cellular suspensions and may represent a viable application for the development of innovative diagnostic devices.

Highlights

  • Various diagnostic techniques have been developed over the last decades, where biochemical markers were investigated to assess the presence and stage of the disease

  • Using atomic force microscopy (AFM) they could discriminate between primary benign prostate hyperplasia (BPH) and two well-characterised and widely used prostate cancer cell lines, LNCaP and PC-3

  • We report the results of the mechanical characterisation and phenotyping of prostate cell lines: PNT2, commonly used as healthy control cells and DU145, known to possess a moderate metastatic potential[22]

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Summary

Introduction

Various diagnostic techniques have been developed over the last decades, where biochemical markers were investigated to assess the presence and stage of the disease. An earlier work by Faria et al.[8] showed how prostate cells of different stages in the disease progression can be discriminated based on their elastic properties. Using atomic force microscopy (AFM) they could discriminate between primary benign prostate hyperplasia (BPH) and two well-characterised and widely used prostate cancer cell lines, LNCaP and PC-3. They were not able to find any mechanical difference between normal PNT2 and PC-3 cell lines which are known to have the highest metastatic potential[22]. We describe a microfluidic device capable of characterising the time-resolved deformability of single cells subjected to hydrodynamic stress. We classified the two cell groups as a result of their different temporal mechanical response using a decision tree classifier

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