UNC Chapel Hill's Computer Integrated Systems for Microscopy and Manipulation facility is an NIH-funded National Research Resource. U.S. researchers doing suitable investigations in the biological sciences are invited to use the facility to carry out their experiments. This page describes the available resources and application procedure. 

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Available Resource: nanoManipulator

• NanoManipulator:  The nanoManipulator is a modified Atomic Force Microscope with which the sample can be not only imaged but also manipulated in a controlled matter. It is realized by interfacing a hand-held force stylus with the scanning tip of the microscope. When the microscope is switched to manipulating mode, the scanning tip moves according to the motion of  the hand-held stylus, thus enabling controlled manipulation of the sample. The manipulation force, speed and direction of manipulation are under total user control. After a manipulation, the microscope can be switched back to imaging mode to view the manipulation. This cycle can be repeated as desired.  Furthermore, all features encountered by the tip can actually be felt by the user in the hand-held stylus, as it is connected to the scanning tip by an integrated force feed-back loop. While the manipulation is done, several parameters of interest (modifying force, lateral force [friction], topography, and others) are recorded simultaneously.   This system has already provided results in manipulating experiments on tobacco mosaic virus (Falvo M. R., et al., Biophys. J. 72 1396-1403 (1997)), Adenovirus (Rajeev insert ref), fibrin, mucin, and  carbon nanotubes (Falvo M. R. et al., Nature 389 583-584 (1997)). For more references click here.
• Topometrix Discoverer and Explorer:   The nanoManipulator can be connected to a Topometrix Discoverer or Explorer.
• Imaging in buffer:  For most biological samples it is imperative to image the samples in buffer to assure their integrity and activity. Our system can be operated in liquids or in ambient conditions. It is, therefore, possible to conduct all imaging and manipulation experiments in buffers with a wide range of salt, pH or other parameters. In addition to the regular contact or oscillating imaging modes, which are standard for all microscopes, we also have recently implemented a novel magnetic tapping mode which makes imaging in liquids easier and more reliable.
  
• Equipment and facilities for sample preparation: Our facility has the necessary equipment for most sample preparations such as nanopure water, substrates (mica, silicon, graphite, glass and others), common chemicals for sample preparations, ingredients for biological buffers, bench space for visitor, pipettes, centrifuges, tubes, freezer, refrigerator and other standard lab equipment.  We also have the necessary accessories for Scanning probe microscopy work and a large variety of cantilevers (NT-MDT, Nanosensors, Park Scientific).

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Available Resource: 3D Magnetic Force Microscope

• 3DMFM:  The 3D Magnetic Force Microscope is a combination optical/magnetic microscopy and manipulation system designed for operation inside liquids. [Rajeev, insert picture from Rich's 3DFM page here of Jeremy holding the pen]. This instrument has been used to track 1 micron beads attached to beating cilia on lung epethelial cells while forces were applied to modify the trajectories of the beads. [Rajeev, Rich should fill in the rest of this section.]

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Some Experimental Results

Manipulation experiments on biological samples

Manipulation of DNA

These two images show a controlled manipulation of two 1100 bp long DNA fragments. The left image shows the fragments before the manipulation; the black arrow indicates the path of the tip during the manipulation process. The right image shows the two fragments after the manipulation (rupturing) of these fragments.  In these experiments a DNA rupture force of about 500 pN was measured. Image size: 300 nm.  (Images: Martin Guthold)

Manipulation of adenovirus

The image sequence below shows a manipulation of the adenovirus in the center of the image.  The two virus particles above it may be used as stationary reference points.  The virus particle underwent two controlled pushes from left to right. These images were taken in buffer with the magnetic tapping mode.  In the future we would like to measure the interaction of these viruses with different funtionalized surfaces. Size of virus particle: ~ 90 nm. (Images: Garrett Matthews)
 
   

 Manipulation of tobacco mosaic virus (TMV)

Controlled dissection and manipulation of TMV particle on graphite. The sequence shows the TMV particle in its original position and orientation (a), then dissected, (b), rotated, (c), translated, (d), and straightened so that it is parallel with the remaining TMV piece, (e) and (f). The vertical line in (a) is a graphical tool indicating the location of the AFM tip while manual control is being employed. (Images: Michael  Falvo)

 
Ridge of manipulated TMV and a fitted equation to calculate elastic properties of TMV.

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Application Procedure

If you are interested in using our facility, please submit a brief statement of the intended research to Dr. Timothy O'Brien. The statement should outline the proposed research and how use of the nanoManipulator and/or 3D Magnetic Force Microscope will benefit the experiments. It can be submitted electronically via e-mail or fax, or just via regular mail.  Please also contact Dr. O'Brien if you have any questions about the facility.
Address:   Dr. Timothy O'Brien
                University of North Carolina
                Department of Computer Science
                Sitterson Hall CB 3175
                Chapel Hill, NC 27599-3175
                e-mail: etobrien@email.unc.edu
                Office: (919) 843-2798
                Fax: (919) 962-0480

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Costs

All the services, assistance, expertise and use of the facility are provided  for free as part of our resource.  Other incurred costs, namely travel, hotel  and used, non re-usable items (such as scanning tips) will be borne by the visitor.