Introduction to quartz crystal microbalance on cancer detection - PowerPoint PPT Presentation

Introduction to quartz crystal microbalance on cancer detection Che Sun, Xinya Su, Yang yu

MEMS1082-Final Report Introduction Theory Transduction Mechanisms Transducer Fabrication Process Flow Device Characterization Device Performance Analysis

MEMS1082-Final Report-Introduction General Background

MEMS1082-Final Report-Introduction Definition of QCM-D

MEMS1082-Final Report-Introduction MEMS1082-Final Report-Introduction History Günter Sauerbrey

MEMS1082-Final Report-Introduction MEMS1082-Final Report-Introduction Current Status

MEMS1082-Final Report-Introduction MEMS1082-Final Report-Introduction Future Trends

MEMS1082-Final Report-Theory Theory

MEMS1082-Final Report-Theory Transduction Mechanism • “Piezo-electric effect”: Mechanical strain -> electric potential • Apply electric potential -> Oscillate -> resonant frequency • As mass is deposited on the surface of the crystal, the thickness increases; consequently the frequency of oscillation decreases from the initial value.

MEMS1082-Final Report-Theory Transduction Mechanism • the resonant frequency is highly sensitive to mass change ' ∆" = − 2" ∆+ & , ( ) * )

MEMS1082-Final Report-Theory Cancer Detection • 1. Percentage of ”signal constituents” high-affinity EDFG • 2. Cell surface difference Surface of abnormal cell is softer than normal cell https://www.youtube.com/watch?v=kzmB K9mONq8&list=PLTszL1x5w9QIRQXfv7tPU fg0ClxkSkfnt

MEMS1082-Final Report-Theory Target Cell Detection Stage 1 Stage 3 Stage 2 Stage 4

MEMS1082-Final Report-Theory QCM Fabrication Prepare AT-cut • crystal • Sputter material to define vibration area • Sandwich product with electrodes on top and bottom

Modification for various purposes • Non-damage manipulation & label-free detection for detecting cancer cell (Passive detection mode) Nickel pillar array surface modified QCM Topped with PDMS Nickle pillar array - generating trapping force under a external electric field PDMS microchannel – providing a secure environment to keep the sample reagents fresh Figure [3] photograph image of the microfluidic system integrated with surface modifies piezoelectric sensor.

Modification for various purposes • For multiple sensing system(different thickness-> frequencies): One-chip Multichannel QCM sensor fabricated by deep reactive ion etching (Deep RIE) Sensor with different coating films can be applied to multiple sensing system such as chemometric odor sensor

Modification for various purposes • Improve sensitivity, convenience, portability and able to provide quick results (real-time measurement) Anodic aluminum oxide (AAO) nanostructure is fabricated on the electrode of a QCM based sensor to achieve these goals by enlarging absorption surface area

MEMS1082-Final Report-Theory Device Characterization • Non-invasive and label-free character. The minimal vibrational amplitude on lateral motion could be less than 1 nm and, and there is no need to incorporate chemical labels such as fluorescent moieties. • High sensitivity and excellent time resolution. These attributes allow detailed assessment over time of diverse cellular functions. • Finite sensing depth. The sensing depth in liquid medium is less than 250 nm from the sensor surface, thereby localizing detection to the basal region of the cell layer, a region that cannot be readily isolated for study with techniques used in cell research.

MEMS1082-Final Report-Theory Device Characterization • Simultaneous measurement of more than one property of the cell. In addition to frequency changes, it records simultaneously the energy dissipation factor( Δ D). The maximum frequency penetration depth is on the order of 250 nm in water and decreases when viscoelastic material is absorbed on the surface. • Ease of use. The data are readily viewable in real time while the measurements are being made

MEMS1082-Final Report-Theory Device Performance Analysis For tumors, increase in cell motility has often resulted in a more aggressive phenotype of tumor cells. To explore the capability of the QCM in assessing motility of tumor cells, Tarantola et al. used subtle fluctuations in frequency tracked by the QCM over time as an indicator of micromotility. Figure 3.5.1 the QCM based sensor system

MEMS1082-Final Report-Theory Device Performance Analysis The thickness shear mode resonator is driven by a signal generator and periodically disconnected. An operational amplifier feeds the signal into an A/D-card used to follow and store the free oscillation decay. The decay curves are subject to non- linear fitting which provides the resonance frequency and the decay constant (as a measure for energy dissipation) of the oscillation. Figure 3.5.1 the QCM based sensor system

MEMS1082-Final Report-Theory The raw data plot • Typical time course of Df and Dd as recorded in a D-QCM experiment after addition of 6-7 105 HT-29 cancer cells; the grey background denotes the time regime of attachment and spreading, whereas the green background highlights the cell monolayer in its confluent state.

MEMS1082-Final Report-Theory The raw data plot • The labels Df and Dd denote the maximal shifts in frequency and dissipation. Fluctuations in frequency/dissipation can be extracted from fixed time intervals. Subsequent Fourier transform analysis provides the PSD (power spectral density). Slopes of the PSD curves in the frequency regime from 0.0005 to 0.005 Hz are used as one quantitative parameter to describe cell motility as are variance and detrended fluctuation analysis.

MEMS1082-Final Report-Theory Thank You