Abstract

Although high strain and strain-rate impacts to the human body have been the subject of substantial research at both the systemic and tissue levels, little is known about the cell-level ramifications of such assaults. This is largely due to the lack of high throughput, dynamic compression devices capable of simulating such traumatic loading conditions on individual cells. To fill this gap, we developed and characterized a high speed, high actuation force, magnetically driven MEMS chip to apply stress to biological cells at unprecedented strain (10% to 90%), strain rate (30,000 to 200,000 s−1), and throughput (12,000 cells/min). To demonstrate the capabilities of the $\mu $ Hammer, we applied biologically relevant strains and strain rates to human leukemic K562 cells and then monitored their viability for up to 8 days. We observed significantly repressed proliferation of the hit cells compared to both unperturbed and sham-hit control cells, accompanied by minimal cell death. This indicates success in applying cellular damage without compromising the overall viability of the population, allowing us to conclude that this device is well suited to study the subtle effects of impact on large populations of inherently heterogeneous cells. [2019-0132]

Highlights

  • A T THEIR most basic level, cells are transducers – entities that receive signals from their environment and transform them into actions that alter the states of the cells and their surroundings

  • Such parameters are useful for probing low force cellular processes and characteristics, but fall short of replicating the loading conditions of external impacts transmitted to brain cells during a Traumatic Brain Injury or to connective tissue cells during skeletal movement

  • A simpler and more effective approach is through pulse width modulation (PWM), which produces a square wave with the same amplitude as steady state (SS), but with adjustable on and off times

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Summary

INTRODUCTION

A T THEIR most basic level, cells are transducers – entities that receive signals from their environment and transform them into actions that alter the states of the cells and their surroundings. The effects of mechanical force have been explored on numerous cell types subjected to a variety of loading conditions including dynamic compression, cyclic tensile loading, and subsonic vibration [4]–[11] Such experiments are common on tissue and groups of cells embedded in synthetic matrices, they are rarely performed on individual cells in vitro. The existing device platforms that are capable of applying compressive forces to individual cells (e.g. AFM, magnetic tweezers, microplates) are each limited to some combination of low force magnitude (sub-μN), strain (

Channel and Impact Face Design
Spring Design
Magnetic Assembly Design
DEVICE FABRICATION
Strobing μHammer Actuation
Validating Pre-Arrival Time
Device Hit Severity Parameters
DEVICE IMPLEMENTATION
Membrane Damage and Cell Death Assay
Apoptosis Assay
Proliferation Study
DEVICE APPLICATIONS
Findings
CONCLUSIONS
Full Text
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