Nanotechnology, Biomolecular Electronics
Biomolecular Electronics and Self-Assembly
Are These Technologies ready for Commercialization?
In a article by Felix Hong (Sixth Newsletter of Molecular Electronics and BioComputing, 1996), he asks the question "Can a single molecule possess intelligence?" In discussing this question he suggests that because of the limited capabilities of computers, scientists are beginning to seek inspiration from biology. Living organisms operate with functional elements that are of molecular dimensions and that exploit quantum and thermal fluctuation phenomena.
Biomaterials had not been seriously considered for the construction of electronic devices until Nikolai Vsevolodov and his colleagues first produced an imaging device and microfilm made from biological materials called Biochrom film. The key substance was bacteriorhodopsin. Since this first study, several attempts to produce imaging and information storage devices using biological materials have been published. Many of these publications have come from the laboratory of Robert Birge at Syracuse University where he has developed a three dimensional information storage device that incorporates bacteriorhodopsin as the storage element.
With the availability of self-assembling membrane systems (SAMs) the stage has been set for the rapid development of biomolecular electronic devices and their assembly using SAM type technologies. As an example, it is obvious that a biological motor cannot be assembled in any way that could be commercially viable other then through a self-assembling process.
Biological molecules, particularly proteins and lipids have all the basic properties necessary for the assembly of nanoscale electronic devices. These biological materials conduct current, transfer molecules from one location to another, are capable of major color changes on application of current or light and can produce cascades that can be used for amplification of a optical or electronic signal. All of these properties can be applied to electronic switches, gates, storage devices, biosensors and biological transistors to name just a few.
The following white paper prepared by Dr. Steven Kornguth, University of Texas is an attempt to look at biomolecular electronics as a technology or group of technologies ready for exploitation.
After reading this document, comments and additional papers would be most welcome. Those that add to the present white paper will be added to the website for further reading and discussion. It is the hope of ATP that commercial firms and their partners both in industry, government and academia will consider the possibilities of this technology area for further research and development. ATP looks forward to further discussions of this topic and to proposals that suggest applications that will lead to commercialization. Further detailed information is available on this ATP website.
Nanotechnology and Biomolecular Electronics
The rapid advances experienced during the past two decades in biotechnology, electronics and computer systems provide new opportunities for convergent technology development utilizing all three sectors. One of the major developments in biotechnology has been the characterization of the structural/functional correlates of biopolymers. This white paper addresses the potential uses of biopolymers as self-assembling monolayers, as electronic and photonic conductive elements and as molecular motors. Interest in the material properties of biopolymers arises from 1) their self assembly properties; 2) their low cost of production in single cell growth chambers; 3) the environmental compatibility of aqueous systems used for biopolymer production in cell culture and 4) the ability to use genetic engineering for transfer of genes to bacteria or plants. The self assembling monolayers can serve as matrices for electronic and photonic conductive elements having 1-10 nanometer thicknesses and mm lengths. Biopolymers can function as transducers of light to electric pulses (photon/electron transducers) with applications in information storage and retrieval. Some biopolymers function as molecular motors having dimensions on the 10 nanometer scale. The technological challenges that must be overcome for cost effective production of end items will also be considered.
Biopolymers and biomimetics have several advantages over many other materials. Many have evolved with the capacity to self-assemble into organized structures. The dimensions of the biopolymers and of functional biopolymeric assemblies (e.g. molecular motors, electron/photon conducting elements, light transducers) are on the nanometer scale (10s of Angstroms). The instructions for synthesizing biopolymers resides in the genetic code (DNA) of living organisms. Current genetic engineering tools allow specific DNA sequences from one organism to be inserted into another organism thereby resulting in large scale production of such materials in cell growth chambers/fermenters and in aqueous systems that are environmentally compatible.
Electron and photon conducting biopolymers have been selected for properties of self- assembly in membrane systems. Biological organisms convert the energy released by oxidation of foodstuffs (protein, lipid and carbohydrate) into a common energy rich compound, adenosine triphosphate (ATP), by a process involving electron transfer in and proton transfer across membranes of mitochondria. The polymers involved in the electron transfer processes are proteins containing a functional heme (i.e. metallo porphyrin) group. These proteins are embedded in phospholipid bilayers that provide boundaries for the transfer of electrons and protons in a vectoral manner.
The primary challenges to be overcome include the need to:
Self-Assembling MonolayersSelf assembling monolayers (SAM) can be prepared using biopolymers deposited in an ordered manner and uniform thickness on elastomers, silicates, gold or other metallic monolayers. One method for the preparation of SAMs involves reacting omega thiol alkane carboxylic acids with a monolayer of gold deposited on a stable matrix (Jordan, Frey, et al. Langmuir 10: 3642-3648 1994; Frey, Jordan et al. 1995 Analytical Chemistry 67: 4452-4457 1995; Kornguth, Corn, et al. U.S. Patent No. 5629213. May 13, 1997. US Patent Office). A co-valent linkage forms between the thiol functional group and gold. A uniform carpet of carboxylated fatty acids is generated creating a polyanionic surface. Polycationic compounds (e.g. polylysine) may then be deposited electrostatically on the carpet, resulting in a uniformly coated surface with amine functional groups bound to the polyanionic lipid surface and exposed to the surface. Approximately two amine functional groups are bound to the lipid surface for each amine facing the aqueous solution. The free amino groups (i.e. not bound to the surface) may be coupled to oligonucleotides, antibodies, other proteins, porphyrins/phthalocyanins. The resulting antibody and oligonucleotide platforms may serve as sensors for biomedical, biodefense or environmental monitoring. The proteins/porphyrins/phthalocyanins that are bound to the surface may function as electron/photon conductive elements with nanoscale dimensions (Ostuni and Whitesides. Colloids and Surfaces B-Biointerfaces 15: 3-30 1999). One advantage of the thiol alkane-gold complex is the lability of this bond to uv light. With appropriate masks, it is possible to prepare patterned arrays where each single element contains a specific binding entity. One product of this strategy is a multi-array sensor or optical read/write disc. A second product may be a nanoscale electronic/photonic circuit with attendant benefits of miniaturization, low power requirements, high efficiency, low heat generation. Self assembling biopolymers, that form right or left handed helical structures, can be produced. In some cases, the addition of ions changes the helicity of these nanostructures with resulting applications for optoelectronic devices including sensors (Engelkamp, Middelbeek and Nolte Science 284 785-788 1999)
Optical detection systems have been developed using SAMs. One optical detection system relies on surface plasmon resonance (Kornguth, Corn, et al. U.S. Patent No. 5629213. May 13, 1997) to detect changes in the thickness of biopolymers covering a set of thin films comprised of glass, thiol alkane, polylysine and specific high affinity molecular binders. A second utilizes fiber optics coated with a film containing antibodies, oligonucleotides, or receptors. The binding of target to a precoated fiber results in changes in the intensity of light emerging from the evanescent wave. The KD of the binding agents for selected targets approximates 10-8 for antibodies and 10-14 for certain receptors. Amperometric sensor systems have been constructed utilizing SAMs coated with high affinity binders and an electron conducting biomimetic such as polypyrrole (Cosnier, Stoytcheva et al. Anal. Chem 71:3692-3697 1999). The advantages of the SAMs is the low cost of production, and the capability of recycling gold coated glass wafers following irradiation with uv light (uv light dissociates thiol alkane from the gold). The disadvantage is the necessity to maintain alignment of a light source with the surface containing the specific binder (i.e. antibody, antigen, oligonucleotide, toxicant). While not a difficulty in clinical laboratories, this may present a challenge to utilization of the technology in field situations. The development of monolithic sensors, having a light emitter and detector on a common plane, in a microenvironment separated by binder and target, would facilitate construction of a field hardened end item.
Electron/Photon Conductive Biopolymers and Nanotubes
Several biopolymers have well documented properties as organic electron conductors. These materials, exemplified by the cytochrome systems, have tetrapyrrole components (porphyrins) that are usually metal centered. The tetrapyrrole is a highly conjugated system that can interact with other tetrapyrroles in a face to face orientation with P bonding. Using model systems Collman and colleagues (J Amer Chem Soc 102:6027-6036 1980) has demonstrated that electron transfer is maximized when the face-to-face distances are maintained at 5-8 Angstroms. Electron transfer may be mediated both through P stacking and redox of the metal center. Phthlocyanins are biomimetics of porphyrins and these have been shown to exhibit modest electron conductivity when doped (Marks, Science 227:881-889 1985). Amperometric sensors have been constructed utilizing biotinylated polypyrroles (Cosnier et al. Analytical Chemistry 71: 3692-3697 1999) and proteins containing porphyrins (Mizutani, Sato et al. Electrochimica Acta 44: 3833-3838 1999). A challenge presented by this technology is the production of filaments of the heme or phthalocyanine entities in most efficient alignment for electron transfer. The development of biopolymer based molecular switches enable more rapid development of molecular transistors and integrated circuits.
Nucleic acids can function both as organic electron transfer materials and as templates for the deposition of electron conducting metals. The rate of electron transfer through organic conductors is approximately four orders of magnitude slower than through good metallic conductors. Double stranded deoxyribonucleic acid (dDNA) has now been demonstrated to function as an organic electron transfer material ("wire"). The electron transfer is effected through stacking and orientation of the bases (SO Kelley, JK Barton. Science 283: 375-381 1999; Wan, Fiebig et al. Proc Natl. Acad. Sci US, 96: 6-14-6019, 1999; Henderson, Jones et. al Proc. Natl. Acad Sci US, 96: 8353-8358 1999). DNA has also been shown to serve as a matrix for adsorption to gold or silver in the construction of nanowires and sensors (Elghanian, Storhoff et al. Science 277: 1078 - 1081 1997; Braun, Eichen et al. Nature 391: 775 1998). The nanowires are capable of electron conduction as metallic materials. The problems associated with this technology include the formation of uniform diameter and oriented polynucleotide fibers. Methods have yet to be developed for production of an ordered deposition of the "nanowires" (DNA or DNA gold complex with deposited metal)" on a support surface. An end product would be a nanoscale integrated circuit.
Nanotubes have been formed using organic polymers as templates (Rudolph AS, Ratna BR and Kahn B. Nature 352: 52-55 1991). The nanotubes have diameters of 1 nanometer or larger and have utility as molecular tweezers or surface probes (Gimzewski and Joachim Science 283 1683 1999). The molecular tweezers enable one to move single molecules on a solid surface for the construction of sensors and integrated molecular motor systems (Kim and Lieber Science 286: 2148-2150 1999; Baughman, Cui et al. Science 284: 1340-1344 1999). These structures may also be used to map the surface properties (i.e. uniform thickness, electrical conductivity, force required to separate two biomolecular complexes) of thin films (Gimzewski and Joachim Science 283 1683 1999). The nanoscale dimensions of the tubes, their physical strength and electronic conducting properties have utilities in a variety of industries including electronics, biomedicine, communications and QC in the manufacture of thin films. The technical issues to be addressed include mass production of uniformly thick tubules, the deposition of the tubules in an ordered manner and attachment of the tubes to larger electron conducting surfaces.
Living systems require motor devices and energy sources for normal function. Examples of such motors are the protein molecules kinesin and dynein (Howard, Hudspeth and Vale Nature 342 154 1989; Block, Goldstein, Schnapp et al. Nature 348: 348 1990) that serve to propel particles from one portion of a nerve cell to another (the distance to be traversed may be longer than 1 meter), the protein F1-ATPase (Stock, Leslie and Walker Science 286: 1700-1705 1999; Noji Science 282 1844-1845 1998), myosin (Mermall, Post and Mooseker Science 279 527-533 1998) and RNA polymerase (Yin et al. Science 270: 1653 1995; Mehta, Rief et al. ibid). The energy used to drive the motors is present in adenosine triphosphate (ATP), a molecule whose synthesis in mitochondria is coupled to the oxidation of amino acids, carbohydrates and fats. The molecular motors can provide forward propulsion or rotational movement in a preferred direction; these are vectorial in nature (Mehta, Rief, Spudich et al. Science 283: 1689-1695 1999). The direction of the movement by kinesin and dynein are determined by the orientation of tubulin, the molecular matrix that the motors use as tracks
For in vitro applications of molecular motors, some estimate of the force generated is useful. Kinesin moves in steps of 8-16 nm along a tubulin track and movement stalls at loads between 5-7 pN (Mehta, Rief et al. Science 283: 1689-1695 1999). The movement of the kinesin is ATP dependent. Whereas movement of the load slows as a function of increasing load, the rate of ATP hydrolysis does not; this suggests that the increase in load reduces the probability of a mechanical step. The rotational torque required for movement of the F1 ATPase is about 80 pN nm and the energy available from the hydrolysis of a single ATP approximates 100 pN. Therefore the efficiency of this system is high (Noji Science 282: 1844-1845 1998). The actin-myosin system step size is about 10 nm and similar force fields have been identified. The stall force required for stopping the RNA polymerase movement is on the order of 25 pN (Wang et al. Science 282: 902 1998). The RNAP step size is estimated at about 1 base pair separation. All these measurements suggest that the forces involved in the ATP dependent movement of molecular motors are within 1 order of magnitude and are highly efficient. These motors have applications in the design of switching devices and nanometer scale rotary devices.
The scale of the nanomotors (about 2-20 nm) is three orders of magnitude smaller than the advanced micromachined motors (75 microns) generated by X-ray lithography and surface micromachining (H Guckel at the University of Wisconsin-Madison). The biopolymer and biomimetic motors have certain advantages and disadvantages as compared with the LIGA machined devices; novel grafting and SAM technology may however now result in hybrid biomolecular-machined motors. In the hybrid motor, the biopolymer could serve as a light tube switch. The biopolymer would not be expected to control movement of the machined motor to the nanoscale level.
Biopolymers and biomimetic polymers have several materials properties of interest to the industrial sectors of electronics, optics, pharmaceutics. The materials have applications in the design and construction of nanoscale integrated circuits, of laminated structural elements (smart sensor interiors in automobiles, planes and trains), of microsensors that can be embedded in persons or animals or placed on protective clothing. The realization of these opportunities requires solutions to some of the challenges identified in this paper.
The industries affected by the technologies identified above include pharmaceuticals, medicine, food processing, cosmetics, electronics, communications, transportation. The end devices that are envisaged at this time include multi-array sensors, electronic/photonic integrated circuits, read/write discs. The components of devices include molecular light/electron switches, light valves, transistors, drug delivery vehicles. The time is right for the rapid development and exploitation of these new and exciting technologies.
Date created: September 2000
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