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Research Projects

Improving Control of Atomic Force Microscopes for Biomedical Applications

Piers Echols-Jones, PhD candidate in Mechanical Engineering

Advisors:

Igor Sokolov, Mechanical Engineering
William Messner, Mechanical Engineering

The original aim of my research is to design a control system for an atomic force microscope (AFM) that will allow a new highly accurate and reliable method potentially suitable for early detection of cervical cancer viable for use in research and general medical use. In this method, developed in Dr. Igor Sokolov's lab, cervical cells are collected and the cells are imaged in the AFM, producing an adhesion map. Fractal dimensional analysis is conducted on the adhesion map to identify malignancy of the cell.

Figure 1: Histogram of fractal dimensionality for 300 cervical cells [M. Dokukin et. al. 2011]

In Figure 1, we see a clear distinction between healthy cells and cancerous cells. At this time, adhesion fractal dimensionality is the only cellular characteristic that shows such a clear distinction. Despite remarkable accuracy surpassing all existing methods, there is serious deficiency of this method. The time of collecting one adhesion map is too long to be practical. When the AFM scanning velocity crosses a threshold, we start to see artifacts in the adhesion map. Artifacts make that particular map useless for analysis and it can be hard to tell when artifacts start appearing.

Figure 2: Adhesion maps of cervical cells (upper) tip velocity is 0.1 um/s (lower) tip velocity is 0.5 um/s [Maxim Dokukin]

In Figure 2, we can see artifacts in the lower image in the form of streaking or blurring. Images are obtained using Peak Force mode. The cause of the artifacts in this case could be tip-crashing, accidental excitation of piezo or sensor dynamics, or some other reason and investigation is ongoing.

The goal of my proposed research is to investigate control methods to significantly decrease the time of recording the adhesion map. The immediate goals of my research are to study AFM probe tip to cell surface interactions, study non-linear control methods, and to research the effectiveness of this technique on a wide variety of biological and synthetic tissues.

Figure 3: AFM z-direction block diagram, relevant functions inside the subsystem blocks

Figure 4: AFM probe deflection excited at 1ms intervals on flat Si wafer (left) experiment (right) simulation

So far, research has yielded a Simulink (Matlab) simulation of probe dynamics and interactions and control in the z-direction. The block diagram and simulation output can be seen above in Figures 3 and 4. With the exclusion of the small interference frequency, the simulation almost exactly matches experiment.
By solving this problem, the AFM will become a powerful tool in the study of biomimetic materials. For example, a potential application is in studying the manufacture of artificial gecko foot pads. The foot pads have long branching hair-like structures which end in a tip that is on the scale of nanometers, and these hairs adhere to surfaces via the van der Waals force. The AFM is the perfect platform for studying the hair structures; by modeling the hairs as a brush and using an indentation mode, a researcher can extract hair density and thickness in a matter of minutes. A simple height image would quickly reveal defects in the structure as well. As another example, one of the largest hurdles present in the soft robotics community is actuation. Ideally, an actuator would closely mimic living muscle tissue which is lightweight, durable, and contains its own energy source, but so far the combination of these characteristics has eluded researchers. The answer may lie in material science, either in the form of an entirely new material, or a cleverly designed composite material. The AFM is an excellent tool to study layering techniques, local compliance or adhesion, potential gradients, or anything else of importance at the micro- or nano-scale.