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The mechanical properties of the cell nucleus are increasingly recognized as critical in many biological processes. The deformability of the nucleus determines the ability of immune and cancer cells to migrate through tissues and across endothelial cell layers, and changes to the mechanical properties of the nucleus can serve as novel biomarkers in processes such as cancer progression and stem cell differentiation. However, current techniques to measure the viscoelastic nuclear mechanical properties are often time consuming, limited to probing one cell at a time, or require expensive, highly specialized equipment. Furthermore, many current assays do not measure time-dependent properties, which are characteristic of viscoelastic materials. Here, we present an easy-to-use microfluidic device that applies the well-established approach of micropipette aspiration, adapted to measure many cells in parallel. The device design allows rapid loading and purging of cells for measurements, and minimizes clogging by large particles or clusters of cells. Combined with a semi-automated image analysis pipeline, the microfluidic device approach enables significantly increased experimental throughput. We validated the experimental platform by comparing computational models of the fluid mechanics in the device with experimental measurements of fluid flow. In addition, we conducted experiments on cells lacking the nuclear envelope protein lamin A/C and wild-type controls, which have well-characterized nuclear mechanical properties. Fitting time-dependent nuclear deformation data to power law and different viscoelastic models revealed that loss of lamin A/C significantly altered the elastic and viscous properties of the nucleus, resulting in substantially increased nuclear deformability. Lastly, to demonstrate the versatility of the devices, we characterized the viscoelastic nuclear mechanical properties in a variety of cell lines and experimental model systems, including human skin fibroblasts from an individual with a mutation in the lamin gene associated with dilated cardiomyopathy, healthy control fibroblasts, induced pluripotent stem cells (iPSCs), and human tumor cells. Taken together, these experiments demonstrate the ability of the microfluidic device and automated image analysis platform to provide robust, high throughput measurements of nuclear mechanical properties, including time-dependent elastic and viscous behavior, in a broad range of applications.
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This content will become publicly available on November 22, 2025
Continuous Viscoelasticity Measurement of Cell Spheroids via Microfluidic Electrical Aspiration
Measurement of viscoelastic characteristics of cells cultured in 3D is critical to study many biological processes including tissue and organ growth. In this article, we present a unique electrical aspiration method to measure the viscoelastic properties of cell spheroids. A microfluidic sensor was created to demonstrate this method. Unlike the traditional optical aspiration method, the aspiration of the cell spheroids is monitored via monitoring the dynamic electrical resistance change of a symmetrical microfluidic aspiration channel. We first used the microfluidic device to measure the viscoelastic properties of two types of biological tissues derived from calfskin and porcine left ventricular myocardium. The equilibrium elastic modulus and creep time con-stants were measured to be 148.1±24.1 kPa and 76.7±3.5seconds and 64.5±7.7 kPa and 31.4±2.7 seconds respectively, which matched well with reported data. The test validated the principle of the electrical aspiration method. Next, we applied the method for measuring cell spheroids made of human mesenchymal stem cells at different culture stages. The equilibrium elastic modulus and apparent viscosity decreased with increasing culture time. Compared to optical aspiration methods, this microfluidic electrical aspiration method has no reliance on transparent materials and image processing, which thus allows simple set-up, fast data acquisition and analysis. The use of a symmetric aspiration channel and the linear half-space model enable measurements of a large number of viscoelastic properties via a single measurement with higher accuracy. This method will enable high throughput, continuous viscoelastic measurement of cell spheroids as well as other 3D cell culture models in flow conditions without the need for any optical measurements
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- Award ID(s):
- 2232940
- PAR ID:
- 10596747
- Publisher / Repository:
- American Chemistry Society
- Date Published:
- Journal Name:
- ACS Sensors
- Volume:
- 9
- Issue:
- 11
- ISSN:
- 2379-3694
- Page Range / eLocation ID:
- 5875 to 5884
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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