Methods for manufacturing bioelectronic devices

Semiconductor device manufacturing: process – Having biomaterial component or integrated with living organism

Reexamination Certificate

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C438S049000, C438S800000

Reexamination Certificate

active

06815218

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to fabrication of electronic structures involving biological or biochemically components.
2. Background Information
Electronic and electromechanical components are presently fabricated in large, industrial manufacturing facilities that are tremendously expensive to build and operate. For example, semiconductor device fabrication generally requires specialized microlithography and chemical etching equipment, as well as extensive measures to avoid process contamination.
The fabrication processes ordinarily employed to create electronic and electromechanical components are expensive and limited in the quantities, which they can produce. In addition they typically involve harsh conditions such as high temperatures and/or caustic chemicals. The ability to integrate the manufacture of such electronic and electromechanical components with biological and biorganic molecules is becoming increasingly important. An example of this integration is the so-called “biochip,” i.e., an electronically active or readable substrate having a dense array of different biological materials (e.g., DNA probes). Such a chip can be used, for example, to identify samples of interest or to test for the presence of various molecular sequences. See, e.g., U.S. Pat. Nos. 5,605,662, 5,874,219, and 5,837,832.
SUMMARY OF THE INVENTION
The present invention provides an alternative to traditional fabrication of electronic components that is economical, scalable and facilitates incorporation of delicate materials. In particular, the invention utilizes nanoparticles to create, through deposition and pattering, microelectronic devices that incorporate biological materials. As used herein, the term “biological material” means any biological, biorganic, or organic material exhibiting biological activity or capable of interacting with a biologically active material; examples of biological materials include, without limitation, proteins, polypeptides (ranging from small oligopeptides to large functional molecules), nucleic acids, polysaccharides, carbohydrates, enzyme substrates, antigens, antibodies, pharmaceuticals, etc.
In accordance with the invention, one or more biological materials are associated, either by direct chemical bonding or by contact, with electrically active materials provided (at least initially) in the form of nanoparticles. In one aspect the invention exploits the fact that many physical, electrical, and optical properties that appear constant in the bulk of organic and inorganic materials are size-dependent at the very small scales characteristic of nanoparticles. At these sizes—ranging from nearly 1 to 999 nm—the ratio of surface atoms to interior atoms becomes non-negligible, and particle properties therefore lie between those of the bulk and atomic materials. Monodisperse (i.e., uniformly sized) or polydisperse nanoparticles can form stable colloids in appropriate dispersing media, facilitating their deposition and processing in a liquid state. As a result printing technology can be utilized to deposit and pattern nanoparticles.
Furthermore, a key property that changes at small sizes is melting point. The effect is substantial; in some semiconductors, melting points have been observed to drop more than 1000° C. from the bulk material. The melting point depression observed in nanoparticle systems facilitates the low-temperature sintering, annealing, and melting of nanoparticles into crystalline films. As a result, nanoparticles can be printed and heated at low temperatures to form films of the bulk material, in some cases without damage to associated biological materials, or can instead be printed and left in dispersed form to retain the size-dependent properties characteristic of the nanoparticles. Altematively nanoparticles may be printed to form electronic, microelectromechanical or microfluidic devices and then subsequently biological material may be printed or added to form a bioelectronic component.
Unlike conventional electrically active particles, nanoparticles are formed not by grinding, but instead via chemical methods (such as pyrolysis) or physical methods (such as physical vapor synthesis). Nanoparticles useful in accordance with the present invention may be pristine or surrounded by a “capping” group to passivate the surface, alter surface chemistry, facilitate dispersion in a liquid, or, in many applications, to bind a biological material. Following their deposition, nanoparticles can self-assemble to form highly ordered thin films and superlattices that may exhibit multiple phases.
Accordingly, in a preferred embodiment, the invention comprises a method of fabricating a bioelectronic component. In accordance with the method, nanoparticles are surrounded by attached shells of at least one biological material. The nanoparticles may then be deposited (e.g., using a printing process) onto a surface. By associating the deposited nanoparticles with one or more electrical contacts, electrical measurement across the nanoparticles (and, consequently, across the biological material) may be made. The device may include a plurality of layers formed by nanoparticle deposition. The nanoparticles within each deposited layer may be immobilized (by fusing, melting,or annealing the particles into a continuous material, by curing the carrier into a permanent matrix, by surrounding the nanoparticles with bifunctional surface groups that link adjacent nanoparticles, or merely by evaporating the carrier using heat or low pressure) in order to facilitate performance of the intended function. Also within the scope of the invention are components fabricated in accordance with the methods hereof.


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