Date of Completion

5-4-2015

Embargo Period

5-4-2015

Advisors

Quing Zhu, Guoan Zheng

Field of Study

Biomedical Engineering

Degree

Master of Science

Open Access

Open Access

Abstract

Cancer has long been one of the major causes of death worldwide. It has been studied and known that cancer can distort the mechanical properties of cells. Recent advancement in biomechanics refers to a significant relationship between cell stiffness and cell condition. Mechanical stiffness can be used to identify abnormal cell populations as in tumors in detecting cancer and can be employed as a diagnostic parameter for various diseases. In this study, we introduced micro fabrication technology to develop polymer based cantilevers integrated with thin chromium film resistor as a transduction scheme. Cantilevers are beam like micro structures anchored only at one end with the other end freely suspended. When a force or load is applied along the length of the cantilever or at the free end, the cantilever bends and stresses are induced on the cantilever surface which changes the resistance of thin chromium film resistor. A custom built amplifier allows for a sensitive response to the deflection.

Cantilevers with different dimensions and stiffness were calibrated. The force detection was in the range of 5-500μN. The cantilever based sensor was used to find the stiffness of an elastic Polydimethylsiloxane (PDMS) micro pillar of diameter 200μm and height 100μm. The purpose of this experiment was to realize cantilevers to manipulate an elastic micro structure mimicking cantilever manipulation with cluster of cells or cancer spheroid of comparable size. A PDMS film containing micro pillars was fabricated using UV lithography and soft lithography techniques. When the cantilever was moved against the PDMS micro pillar with the help of mechanical stage displacement, the cantilever deflected and the PDMS micro pillar displaced as well. Using the measurements and calculations from cantilever calibration and cantilever manipulation with elastic PDMS micro pillar, the stiffness of elastic PDMS micro pillar of diameter 200μm and 100μm was measured which was 0.97 Nm-1.

The cantilever based sensor was also used to measure force in cancer cell manipulation. The purpose of this experiment was to show the capability of handling cells. A cell holding device was fabricated using UV lithography and soft lithography techniques. The cell holding device was a PDMS film that consisted of a circular well of depth 100μm and PDMS micro pillars of diameter 300μm and height 100μm. MCF-7 cancer cells were centrifuged and an aggregation of MCF-7 cancer cells was pasted onto the circular well of the PDMS film. Using the measurements and calculations from cantilever calibration and cantilever manipulation with aggregation of cancer cells, the stiffness of the whole system consisting of the PDMS film with PDMS micro pillars and aggregation of MCF-7 cancer cells was measured which was in the range 2.0-2.3 Nm-1. A force range of 5-90μN was detected and applied which resulted in indentation of aggregation of MCF-7 cancer cells seen under the microscope.

These cantilever based sensors are compatible to explore the stiffness of cluster of cancer cells or cancer spheroids. These findings suggest that the polymer based micro scale force sensing cantilevers designed, fabricated and tested in this study can be used for biosample manipulation and measurements.

Major Advisor

Kazunori Hoshino

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