Adjustable nanopore, nanotome, and nanotweezer

Etching a substrate: processes – Adhesive or autogenous bonding of two or more...

Reexamination Certificate

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C216S056000, C438S733000

Reexamination Certificate

active

06706203

ABSTRACT:

TECHNICAL FIELD
The present invention relates generally to handling, measurement, and cleavage of objects at the molecular size scale, that is, with handling, measurement, and cleavage of objects with characteristic dimensions on the order of nanometers.
BACKGROUND ART
The art of manipulating individual atoms, molecules, and supramolecular particles is called “nanomanipulation”, and is in a very crude state in the year 2001.
The art of nanomanipulation was first proposed by Richard Feynman on Dec. 29, 1959, at the annual meeting of the American Physical Society in a speech titled “There's Plenty of Room at the Bottom”, in which he noted that
“The principles of physics, as far as I can see, do not speak against the possibility of maneuvering things atom by atom. It is not an attempt to violate any laws; it is something, in principle, that can be done; but in practice, it has not been done because we are too big.”
Feynman, the winner of the 1965 Nobel Prize in physics, further noted in his 1959 speech that “The problems of chemistry and biology can be greatly helped if our ability to see what we are doing, and to do things on an atomic level, is ultimately developed—a development which I think cannot be avoided.”
However, progress in nanomanipulation has been slow.
The scanning tunneling microscope (STM) was developed in 1980; see U.S. Pat. No. 4,343,993. The STM provides, in essence, a means of shoving around atoms and molecules on a slab with a pointy stick. It also provides a crude sense of touch. The atomic force microscope (AFM) was developed subsequently and provides another means of shoving atoms and molecules on a slab with a pointy stick, and also provides a crude sense of feel. Other proximal probe microscopy (PPM) techniques were developed subsequently; all consist of a pointy stick whose tip position is controlled and monitored, and which can report on the profile and properties of a surface over which the stick is dragged. The usual means of controlling the stick's tip position is a three-axis piezoelectric driver, and the usual means of sensing the tip position is a combination of sensing the voltages applied to the piezoelectric driver and sensing some other quantity such as tunneling current, piezoresistive change, or optical reflection occurring as close as possible to the tip. Scanning probe techniques have been combined with electron microscopy to provide additional sensing means; see, for example “Three-dimensional manipulation of carbon nanotubes under a scanning electron microscope”, by MinFeng Yu et al,
Nanotechnology
, Vol. 10, no. 3, pp. 244-252 (September 1999).
More recently, naturally occurring pores in cell membranes have been used to characterize long-chain molecules; see, for example, U.S. Pat. No. 5,795,782. These pores have fixed dimensions on the order of nanometers. Subsequently, artificially-produced nanopores of fixed dimensions have been developed for the same purpose. Both types of pores have been used to sense the passage of individual long-chain molecules such as DNA molecules, and have provided some information on the structure of such molecules. The “holy grail” of these techniques, not yet achieved, has been to sense the structure of a molecule passing through a pore to a level as fine as the individual bases in a DNA strand.
The usual means of sensing the passage of a molecule through the pore is to monitor ionic current through a solution filling the pore when a voltage is applied. Reduction in a maximum current implies that the pore is partly blocked by the cross-sectional area of a molecule. Charged molecules float freely in solution, and at random times are pulled through the pore by an electric field existing in the solution. One problem with these techniques is that the passage of an individual molecule through a pore cannot be precisely predicted or controlled; it is a random, stochastic event, and when a molecule enters the pore, it zips through quickly.
Thus, there still exists a need for other means of manipulating and sensing atoms and molecules, and other entities larger than molecules.
DISCLOSURE OF INVENTION
The present invention forms an adjustable nanopore, nanotome, or nanotweezer by placing two substrates in close contact such that they form a small adjustable aperture through which a continuous path extends. A first substrate has a first edge situated at a first surface of the first substrate, the first edge having a first region of sharp curvature in the plane of the first surface. A second substrate has a second edge situated at a second surface of the second substrate. The first surface is placed in close contact with the second substrate such that the first edge and the second edge combine to form an arched aperture, the first edge forming the arch, the first region of sharp curvature forming the crown of the arch, the second edge forming the base of the arch, and the two closest approach points of the first and second edges forming the springing points of the arch. The second edge may be straight, or may be curved either convexly toward or concavely away from the first edge. The second edge can be moved with respect to the first edge, using an adjustable movement mechanism, to vary the height of the arch, the area of the arch, and the shape of the arch. The width of the aperture is defined as the diameter of the largest sphere which can pass through the aperture, and this width can be one hundred nanometers and less. The arched aperture can be usefully employed in characterizing, sorting, sieving, cleaving, and holding nanometer-scale substances including molecules, molecular complexes, and supramolecular complexes, and mixtures thereof.
In accordance with several embodiments of the present invention, two monolithic substrates are provided, each having a through-hole, with the first through-hole in the first substrate intersecting a first surface at a first edge, the first edge having a corner region of sharp curvature in the plane of the first surface with a radius of curvature on the order of 3 nanometers, the first through-hole and the first edge being preferably formed by orientation-dependent etching. The second through-hole in the second substrate intersects a second surface at a second edge, and the second hole and second edge are also preferably formed by orientation dependent etching. The first surface is placed in contact with the second surface such that the first edge and second edge combine to form an arched aperture of substantially triangular cross section, the corner region in the first edge forming the crown of the arch or the apex of the triangle. A mechanism is provided to move one substrate relative to the other so as to adjust the size and shape of the aperture.
In one embodiment (nanopore), the first edge and the second edge combine to create a pore of adjustable area and substantially triangular cross section through which a molecule can pass, so as to provide information about the molecule or to separate molecules of different dimensions, such as separating straight-chain hydrocarbons from branched hydrocarbons.
In a second embodiment (nanotome), the first edge and the second edge combine to create a pore of adjustable area and substantially triangular cross section around a stretched long-chain molecule. The area of the pore is then reduced to create a shearing action so as to cut the molecule at a desired point.
In a third embodiment (nanotweezer), the first edge and the second edge combine to create a pore of adjustable area and substantially triangular cross section around a stretched long-chain molecule. The area of the pore is then reduced to capture the molecule at a desired point without cutting it.
In the three embodiments discussed above, the arched aperture is substantially triangular (symmetrical or asymmetrical), and the height of the triangle is altered by moving one element relative to the other, e.g., moving the second edge (base) closer to or further away from the corner (crown or apex) in the first edge.
Alternatively, a second corner region of sharp curvatu

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