Abstract:
A detection device containing of a hybrid nucleic acid assembly. The device contains a nucleic acid polymer, a first complementary oligonucleotide annealed to a first consensus sequence on the nucleic acid polymer, a second complementary ogligonucleotide annealed to a second consensus sequence on the nucleic acid polymer, a first nanoparticle conjugated with the first complementary oligonucleotide, a second nanoparticle conjugated with the second complementary oligonucleotide, means for introducing energy into the first nanoparticle, means for withdrawing energy from the second nanoparticle, means for detecting the withdrawal of energy from the second nanoparticle, and means for determining a physical property of the nucleic acid polymer while energy is introduced into the first nanoparticle.

Description:
FIELD OF THE INVENTION  
         [0001]    An assembly comprising a strand of nucleic acids joined to a signal transceiver, such as an electrically conductive carbon nanotube device.  
         BACKGROUND OF THE INVENTION  
         [0002]    In an article by Hans-Werner Fink and Christian Schonenberger, published in Nature (Volume 398, Apr. 1, 1999, at pages 407-410), the authors stated that: “The question of whether DNA is able to transport electrons has attracted much interest . . . . Experiments addressing DNA conductivity have involved a large number of DNA strands doped with intercalated donor and acceptor molecules, and the conductivity has been assessed from electron transfer rates as a function of the distance between the donor and acceptor sites. But the experimental results remain contradictory, as do theoretical predictions.” 
           [0003]    The prior art techniques for measuring DNA conductivity are relatively crude; with many of such techniques, the acts of measurement influence the very variables being measured.  
           [0004]    Additionally, to the best of applicants&#39; knowledge, none of the prior studies of DNA conductivity measured such conductivity with the DNA in an environment similar to its natural environment.  
           [0005]    It is an object of this invention to provide a process for measuring DNA conductivity which is substantially more accurate than prior art processes.  
           [0006]    It is another object of this invention to provide a process for measuring DNA conductivity (of electrons, photons, and vibration) while such DNA is undergoing its normal processes (such as transcription or replication) in substantially its normal environment.  
           [0007]    It is another object of this invention to provide a process for measuring the shape structure of DNA.  
           [0008]    It is another object of this invention to provide a novel hybrid nucleic acid assembly useful in practicing the processes of this invention.  
         SUMMARY OF THE INVENTION  
         [0009]    In accordance with this invention, there is provided a hybrid nucleic acid assembly comprised of a partially denatured double strand of nucleic acid, a first probe attached to a proximal end of such strand, and a second probe attached to a distal end. Each of the first and second probes is comprised of a conductive fiber. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    The present invention will be described by reference to the following drawings, in which like numerals refer to like elements, and in which:  
         [0011]    [0011]FIG. 1 is a flow diagram of one preferred process of the invention;  
         [0012]    [0012]FIG. 1A is a flow diagram of a process for making certain transceivers;  
         [0013]    [0013]FIGS. 2A, 2B, and  2 C are schematic representations of various transceiver assemblies which may be used in the process of the invention;  
         [0014]    [0014]FIGS. 3A and 3B are schematic diagrams of a measurement device utilizing the hybrid nucleic acid assembly of FIG. 2; and  
         [0015]    [0015]FIG. 4 is a flow diagram of an imaging process for detecting the shape structure of DNA. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0016]    [0016]FIG. 1 is a flow diagram of one preferred process of the invention. FIG. 1A is a schematic diagram illustrating how preferred oligonucleotide assemblies used in the process of FIG. 1 may be assembled.  
         [0017]    Referring to FIG. 1, and in the preferred embodiment depicted therein, in step  10  of the process, a single strand of nucleic acid  12  is attached to a reactive surface  14  comprised of reactive sites  16 ,  18 , and  20 .  
         [0018]    One may prepare single stranded DNA by conventional means, such as, e.g., cDNA preparation techniques; see, e.g., U.S. Pat. Nos. 6,184,017, 6,180,612, 6,180,385, 6,177,244, and 6,172,197, the entire disclosure of each of which is hereby incorporated by reference into this specification.  
         [0019]    The single stranded DNA used in the process depicted in FIG. 1 is the sequence to be analyzed. It may, e.g., contain promoter and/or enhancer regions, structural genes (including introns, exons, and the like), etc.  
         [0020]    It is preferred that the single stranded DNA  12  be purified, i.e., it be substantially homogeneous. DNA purification may be effected by conventional means; see, e.g., U.S. Pat. Nos. 6,187,578, 6,187,575, 6,187,564, 6,187,559, 6,187,552, and the like, the entire disclosure of each of which is hereby incorporated by reference into this specification.  
         [0021]    Reactive surface  14  may be any surface commonly used in the preparation of DNA chips. Such DNA chips are well known and are sold, e.g., by the Affymetrix Company, by the Incyte Company, etc. Alternatively, the reactive surface  14  may be a passive derivatized polymeric or glass surface. The preparation of derivatized reactive surfaces is well known; see, e.g., U.S. Pat. Nos. 5,641,539, 5,453,199, 5,372,719, and the like, the entire disclosures of each of which is hereby incorporated by reference into this specification.  
         [0022]    In one embodiment, the reactive surface  14  is described in an article by Brett A. Stilman et al. Entitled “FAST Slides: A Novel Surface for Microarrays” appearing in the September, 2000 edition (Volume 29, No. 3) of BioTechiques, at pages 630-635.  
         [0023]    Referring again to FIG. 1, one may attach single stranded DNA  12  to reactive surface  14  by conventional techniques. Thus, by way of illustration and not limitation, one may attach strand  12  to surface  14  by covalent bonding. See, e.g., U.S. Pat. Nos. 5,472,888 and 6,177,247, the entire disclosure of each of which is hereby incorporated by reference into this specification.  
         [0024]    In step  22 , another strand of preferably purified DNA  13  is attached to reactive surface  15 , which preferably has characteristics similar to surface  14  but may differ therefrom. It is preferred that DNA strand  13  have a base sequence that differs from DNA strand  12 . As will be apparent to those skilled in the art, DNA strand  13  also is derived from the DNA to be analyzed.  
         [0025]    In another embodiment, two different reactive surfaces are used to bond to DNA strands  12  and  13 , respectively.  
         [0026]    In one embodiment, strands  12  and  13  have similar base sequences. What is required however, in all embodiments, is that end  24  of strand  10  and end  25  of strand  13  have complementary base pairs to facilitate annealing therebetween.  
         [0027]    In one preferred embodiment, depicted in FIG. 1, each of steps  10  and  22  occur in different environments, such as, e.g., separate test tubes. In this embodiment, two distinct, noncontiguous reactive surfaces are used.  
         [0028]    In step  26  of the process, an oligonucleotide  28  is annealed to DNA strand  12  by conventional means; see, e.g., U.S. Pat. Nos. 6,083,723, 6,083,698, 6,051,379, 6,017,731, 5,972,604, and the like, the entire disclosure of each of which is hereby incorporated by reference into this specification. As will discussed in detail elsewhere in this specification, oligonucleotide  28  (and oligonucleotide  29 ) is attached to a device, which is capable of generating an electrical or magnetic or optical signal or otherwise transmitting information.  
         [0029]    It is preferred that oligonucleotide  28  contains base pairs complementary to the base pairs in the region of DNA strand  12  to which oligonucleotide  28  is to be annealed. Similarly, oligonucleotide  29  preferably contains base pairs complementary to a region of DNA strand  13 ; and in step  28  oligonucleotide  29  is similarly annealed to DNA strand  13 .  
         [0030]    In steps  30  and  32 , the annealed DNA strands  12  and  13  are optionally caused to be released from reactive surfaces  14  and  15 , respectively. This is preferably done by the breaking of the chemical bond between strands  12 / 13  and surfaces  14 / 15 . This breaking may be effected by conventional means such as, e.g., restriction enzyme cleavage.  
         [0031]    In one embodiment, step  30  and/or step  32  is omitted. In one embodiment, only one of strands  12  or  13  is released. Thus, e.g., one may have a situation in which the bond energy between strand  12  and surface  14  is substantially greater than the bond energy between strand  13  and surface  15 , in which case the latter bond is preferentially broken after strands  12  and  13  are hybridized. By way of illustration, surfaces  14  and  15  may exist on a flat or spherical surface (such as, e.g., beads).  
         [0032]    One may cleave the DNA strands  12 / 13  by conventional means such as,e.g., those disclosed in U.S. Pat. Nos. 6,183,993, 6,180,402, 6,180,338, 6,175,001, 6,174,724, and the like; the entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.  
         [0033]    The released strands  12 / 13  which are bonded to oligonucleotides  28 / 29  are then preferably pooled by charging them to the same container, which preferably contains a buffer, such as tris-buffer. Thereafter, in step  34 , the released strands  12 / 13  anneal to each other in mutually complementary region.  
         [0034]    The annealed structure  38  is partially single stranded and partially double stranded. In step  40 , annealed structure  38  is made completely double stranded by exposing it to base building blocks (nucleotides) in the presence of polymerase and ligase, in accordance with standard protocols for DNA vector construction. See, e.g., U.S. Pat. Nos. 4,853,323, 6,184,034, 6,184,000, 6,177,543, 6,171,861, and the like.  
         [0035]    In the embodiments depicted in FIG. 1, oligonucleotides are depicted as being disposed on opposite strands  12  and  13 . In another embodiment, not shown, the oligonucelotides are disposed on the same strands. In yet another embodiment, not shown, the oligonucleotides are disposed on both the same and on opposite strands. Other combinations will be apparent to those skilled in the art.  
         [0036]    Referring again to FIG. 1, the double-stranded structure  42  produced by this process has incorporated within it oligonucleotides  28  and  29 .  
         [0037]    [0037]FIG. 1A illustrates one preferred process for constructing oligonucloetide devices containing oligonucleotide  28  or  29  and, attached to each such entity, an information interface. In step  50  of this process, the desired oligonucleotide  53  with the desired base sequence(s) is constructed by conventional means and/or purchased.  
         [0038]    In step  52  of the process, the oligonucleotide is activated at sites  55  and  57 ; as will be apparent to those skilled in the art, the oligonucleotide activation step is variable. Some of the oligonucleotides are not activated, some are activated at one site, and some or activated at two or more sites.  
         [0039]    The term oligonucleotide activation, as used in this specification, refers to chemical modification of the nucleic acid(s) within the oligonucleotide to enable such nucleic acid(s) to react with another molecule located on a transceiver. One may activate the oligonucleotide by conventional means. Thus, e.g., one may use alkylthio functionalization activation of DNA; see, e.g., an article by Gregory P. Mitchell et al. Entilted “Programmed Assembly of DNA Functionalized Quantum Dots” (Journal of the American Chemical Society, 1999, 121, pages 81232-8123). Thus, one may use methylation of DNA. Thus, e.g., one may use the techniques described in an article by Jens-Peter Knemeyer et al. Entitled “Probes for Detection of Specific DNA Sequences . . . ,” appearing in Analytical Chemistry, Volume 72, pages 3717 to 3724 (Aug. 15, 2000). Thus, e.g., one may use one or more of the activation techniques described in U.S. Pat. Nos. 6,013,789, 5,577,694, 5,747,244, 5,712,383, 5,612,468, 5,525,711, and the like; the entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.  
         [0040]    A suitable transceivor  59 , as defined below, is constructed in step  51 , and the transcivor  59  is activated in step  53  at sites  61  and  63 .  
         [0041]    In a similar manner, the surface of the transceiver may be activated in transceiver activation step  53 . As used herein, the term transceivor refers to any molecule, compound, structure, or article capable of either conducting a signal, transducing a signal from one form to another, initiating a signal, etc.  
         [0042]    By way of illustration, the transceiver may be a metal fiber such as, e.g., a gold fiber. By way of further illustration, the transceivor may be a carbon nanotube fiber, a chromophor (which changes its optical properties upon excitaton), a fluorophor (which also changes its optical properties upon excitation), a lumiphor (which emits photons upon receipt of electrons), a molecular battery (which releases electricity upon photon stimulation), a radio frequency antenna (which receives or transmits radio frequency energy upon excitation), and the like. Additionally, the transceivor may be comprised of a radioactive material whose decay initiates one or more chemical reactions, resulting in the discharge of electrons.  
         [0043]    Regardless of the structure of the transceivor, or its form or composition, it is preferred to activate such transceiver in step  53  so that it will readily bond to the activated oliogonucelotide, preferably by chemical means. The bonding may occur by any known mechanism such as, e.g., by Van Der Waals forces, by ionic forces, by polar forces, by combinations thereof, and the like. In one preferred embodiment, the bonding is effected primarily by covalent bonds.  
         [0044]    Referring again to FIG. 1A, and in the preferred embodiment depicted therein, in step  54  the activated oligonucleotide is reacted with the activated transceiver to produce an assembly adapted to receive information from or transmit information to a DNA sequence.  
         [0045]    In step  56 , the reaction products produced in step  54  may be purified by conventional means such as, e.g., chromatography to insure that the reaction products are substantially homogeneous. See, e.g., U.S. Pat. Nos. 6,187,578, 6,187,585, 6,187,564, 6,187,559, and 6,187, 552; the entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.  
         [0046]    [0046]FIG. 2A is a representation of a transceiver assembly  70  comprised of a double stranded DNA  72  produced in accordance with steps  28  and  40  of the process depicted in FIG. 1. In the embodiment depicted in FIG. 2A, the transceivers  59  are carbon nanotubes which have a length  74  such that they preferably extend out of the environment in which the double stranded DNA  72  is disposed. Thus, for example, if the DNA  72  is disposed within a test tube (not shown), the tops  76  of transceivers  59  preferably extend beyond the top of the test tube. As will be apparent, this feature enables other devices to be readily attached to the tops  76  of the nanotubes  59 ; and it also facilitates the use of such other devices whose use might be interefered with given the physical constraints of the test tube.  
         [0047]    In the embodiment  70  depicted in FIG. 2A, each of the transceivers  59  is a carbon nanotube. In the transceiver assembly  80  depicted in FIG. 2B, each of the transceivers  82  and  83  is a molecule which, preferably, is a fluorophore (a potentially fluorescent group of atoms in a molecule) which will fluoresce upon being excited; see, e.g., U.S. Pat. Nos. 6,187,567, 6,187,566, 6,187,250, 6,184,027, 6,183,984, and the like, the entire dislcosure of each of which is hereby incorporated by reference into this specification. Transceivors  82  and  83  may consist essentially of the same material, or they may consist essentially of different materials.  
         [0048]    If a photon  84  impinges upon the surface  86  of fluorophoric transceivor  82 , the transceiver  82  will emit an electron (not shown) which will travel into the double stranded DNA  72  in the direction of arrow  88  and thence through the DNA  72  in the direction of arrows  90  until it is received by receptor transceivor  82 ′, which attracts it because of a potential difference. When the electron is received by trasceivor  82 ′, it will emit a photon, fluoresce, and then return to its base state potential which existed before it received the electron. As will be apparent, this device enables the construction of more complicated circuits.  
         [0049]    The embodiment depicted in FIG. 2C is similar to that depicted in FIG. 2B with the exception that the transceiver  92  is comprised of a multiplicity of fluorophoric sites  94 ,  96 ,  98 , and  100 . When such a transceiver  92  is excited by a multiplicity of electrons (not shown), it will emit substantially more electrons than the single fluorophore depicted in FIG. 2B; and it will thus cause the transceiver  83  to fluoresce substantially longer and/or more frequently.  
         [0050]    As will be apparent, a photon can cause the emission of an electron in a fluorphoric device. It will be apparent, however, that this process is reversible, and that an electron can cause the emission of a photon from a fluorophoric device.  
         [0051]    One can determine, under normal conditions for a specified double stranded DNA, how much a specified amount of excitation energy causes a current to flow, especially if measuring devices are connected to the transceivers. Consequently, one can determine when there is any aberrant condition with such DNA that would affect such current flow, and/or one can determine when normal DNA processes (such as transcription or replication) are occurring. Reference data can be generated as to the current flows normally existing during these events, and such data can be correlated with readings taken from the DNA when it is in a substantially in vivo environment.  
         [0052]    [0052]FIG. 3A is a schematic representation of a circuit  100  in which transceivers  59  are conductively connected by conductor  102  to form a closed circuit comprised of such transceivers  59 , such conductor  102 , and double stranded DNA  72 . Disposed within such circuit  100  is controller  104  which is capable of sending energy  106  around the circuit  100  in the directions of arrows  108 ,  110 , and  112 . The energy transmitted by controller  104  may be thermal energy, and/or light energy, and/or vibrational energy, and/or magnetic energy, and/or electrical energy. Any of the forms of such energy commonly available or producible may be sent by controller  104 .  
         [0053]    By way of illustration and not limitation, the energy transmitted may be electrical energy that is either direct current energy or alternating current energy. When alternating current energy is sent, it may be amplitude modulated energy, frequency modulated energy, phase modulated energy, and the like. As will be apparent, one may vary the amplitude, voltage, frequency, current, and impedance of such energy, as is well known in the electrical art.  
         [0054]    By way of further illustration., the energy transmitted may be light energy, either in the form of waves and/or particles, at various frequencies, wavelengths, or combinations thereof. In this embodiment, the conductor  102  may be a fiber optic conductor.  
         [0055]    The controller  104 , in addition to emitting energy, also is capable of measuring the characteristics of the DNA between points  114  and  116 . As will be apparent, although only two connection points  114  and  116  are depicted in FIG. 3A, more of such connections could be made so that one could determine the electrical characteristics between any two points on DNA strand  72 .  
         [0056]    The electrical properties of DNA strand  72  will vary depending upon its geometry and chemical composition. These characteristics will, in turn, vary when events such as protein binding, transcription, replication, denaturation, and the like occur. Thus, the circuit  100  may be used to determine when a particular strand  72  of DNA is undergoing such an event and/or whether a particular strand of DNA  72  evidences an aberrant behavior or composition or geometry which affects such electrical characteristics.  
         [0057]    The controller  104  is preferably comprised of a programmable logic chip which enables it to modify its performance upon evaluation of the data it collects from DNA strand  72 .  
         [0058]    In one embodiment, the circuit  100  is disposed in an environment (not shown) which substantially simulates and/or is substantially identical to the environment the DNA strand  72  normally is in. Thus, one may charge circuit  100  to an aqueous environment comprised of buffer, essential biological components (such as nucleotides, adenosine triphosphate, protein enzymes), and the like. Thus, one may ligate circuit  100  into a DNA vector (not shown) by means of linkers  115  and  117 , in accordance with standard biotechnical protocols; see, e.g., U.S. Pat. Nos. 6,187,757, 6,183,753, 6,180,782, 6,136,568, 6,136,318, and the like, the entire disclosure of each of which is hereby incorporated by reference into this specification. Thus, the circuit  100  may be introduced into a functional biological entity such as a bacteria or eukaryotic cell and, thereafter, used to monitor the in vivo activity within the bacterium or eukaryotic cell. As will be apparent, the vector containing circuit  100  can be made part of any nucleic entity (such as, e.g., a plasmid, a chromosome) and, after such modification, undergoes precisely the same occurrences as would an endogenous species. Thus, the circuit  100  may be used to evaluate and monitor and modify a wide variety of in vivo activities.  
         [0059]    When the circuit  100  is disposed within a cell, e.g., and when the oligonucleotides  28  and  29  are disposed on opposite strands  12  and  13 , when such a cell divides, each daughter cell will then receive one end of the circuit  100 , in which case the circuit  100  measures conductivity across two or more cells.  
         [0060]    In another embodiment, not shown, the circuit  100  is encapsulated in a lipid derived delivery system prior to being incorporated within a cell. This technique is well known and is described, e.g., in U.S. Pat. No. 6,187,760, the entire disclosure of which is hereby incorporated by reference into this specification. As is disclosed in such patent, the introduction of foreign nucleic acids and other molecules is a valuable method for manipulating cells and has great potential both in molecular biology and in clinical medicine. Many methods have been used for insertion of endogenous nucleic acids into eukaryotic cells. E.g., see Graham and Van der Eb, Virology 52, 456 (1973) (co-precipitation of DNA with calcium phosphate); Kawai and Nishizawa, Mol. Cell. Biol. 4, 1172 (1984) (polycation and DM80); Neumann et al., EMBO Journal 1, 841 (1982) (electroporation); Graessmann and Graessmann in Microinjection and Organelle Transplantation Techniques, pp. 3-13 (Cells et al., Eds., Academic Press 1986) (microinjection); Cudd and Nicolau in Liposome Technology, pp. 207-221 (G. Gregoriadis, Ed., CRC Press 1984) (liposomes); Cepko et al., Cell 37, 1053 (1984) (retroviruses); and Schaffher, Proc. Natl. Acad. Sci. USA 77, 2163 (1980) (protoplast fusion). Both transient and stable transfection of genes has been demonstrated.  
         [0061]    Some of the first work on liposome delivery of endogenous materials to cells occurred about twenty years ago. Foreign nucleic acids were introduced into cells (Magee et al., Biochim. Biophys. Acta 451, 610-618 (1976), Straub et al., Infect. Immun. 10, 783-792 (1974)), as were foreign lipids (Martin and MacDonald, J. Cell Biol. 70, 5 15-526 (1976)), Proteins (Magee et al., J. Cell. Biol. 63, 492 (1974), Steger and Desnick, Biochim. Biophys. Acta 464, 530 (1977)), fluorescent dyes (Leventis and Silvius), and drugs (Juliano and Stamp, Biochem. Pharm. 27, 2127 (1978), Mayhew et al., Cancer Res. 36, 4406 (1976), Kimelberg, Biochim. Biophys. Acta 448, 531 (1976)), all using positively charged lipids.  
         [0062]    Of the many methods used to facilitate entry of DNA into eukaryotic cells, cationic liposomes are among the most efficacious and have found extensive use as DNA carriers in transfection experiments. See, generally, Thierry et al. in “Gene Regulation: Biology of Antisense RNA and DNA,” page 147 (Erickson and Izant, Eds., Raven Press, New York, 1992); Hug and Sleight, Biochim. Biophys. Acta 1097, 1(1991); and Nicolau and Cudd, Crit. Rev. Ther. Drug Carr. Sys. 6, 239 (1989). The process of transfection using liposomes is called lipofection. Senior et al., Biochim. Biophys. Acta 1070, 173 (1991), suggested that incorporation of cationic lipids in liposomes is advantageous because it increases the amount of negatively charged molecules that can be associated with the liposome. In their study of the interaction between positively charged liposomes and blood, they concluded that harmful side effects associated with macroscopic liposomeplasma aggregation can be avoided in humans by limiting the dosage.  
         [0063]    Feigner et al., Proc. Natl. Acad. Sci. USA 84, 7413 (1987), demonstrated that liposomes of dioleoylphosphatidylethanolamine (DOPE) and the synthetic cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTI VIA) are capable of both transiently and stably transfecting DNA. Rose et al., BioTechiques 10, 520 (1991), tested lipofection with liposomes consisting of DOPE and one of the cationic lipids cetyldimethylethylammonium bromide (CDAB), cetyltrimethylethylammonium bromide (CTAB), dimethyldioctadecylammonium bromide (DDAB), methylbenzethoniurn chloride (MBC) and stearylamine. All of the liposomes (except that with CTAB) successfully transfected DNA into HeLa cells. At high concentrations; however, CDAB and MBC caused cell lysis. Only DDAB was found to be effective in mediating efficient DNA transfection into a variety of other cell lines. Malone et al., Proc. Natl. Acad. Sci. USA 86, 6077 (1989), successfully transfected RNA, in vitro, into a wide variety of cells lines. Zhou and Haung, J. Controlled Release 19, 269 (1992), disclosed successful lipofection by DOPE liposomes stabilized in the lamellar phase by cationic quaternary ammonium detergents. The authors noted, however, that the relatively high cytotoxicity of these compounds would limit their use in vivo.  
         [0064]    Hawley-Nelson et al., Focus 15, 73 (1990, BRL publications), disclosed the cationic lipid “LIPOFECTAMH′4E”, a reagent containing 2,3-dioleyloxy-N-[2(spermineearboxyaniido)ethyl]-N,N-dimethyl-1-propanamin ium trifluoroacetate (DOSPA). “LEPOFECTAMJNE” was found to have higher transfection activity than several monocationic lipid compounds (“LIPOFECTIN”, “LIPOFECTACE”, and DOTAP) in six of eight cell types tested. They observed toxicity when both lipid and DNA were included in the same mixture. These encapsulating agents are sold by Gibco BRL Systems, Inc. of Bethesda, Md.  
         [0065]    Referring again to FIG. 3A, and in the embodiment depicted therein, an antenna  118  is operatively connected to the controller  104  and is adapted to transmit signals in response to instructions from such controller. In one aspect of this embodiment, the antenna  118  emits signals in response to readings taken of the DNA strand  72 . Inasmuch as the electrical properties of DNA strand  72  vary substantially instantaneously when various biochemical events occur, a remote receiver  120  disposed outside of circuit  100  may be used to monitor the status of and the activity of such DNA. This is especially useful when circuit  100  is disposed within a living being.  
         [0066]    [0066]FIG. 3B depicts a circuit  130  similar to circuit  100  but differing therefrom in that the energy  132  is introduced from a source remote from circuit  130 . One may use any conventional remote energy source such as, e.g., a laser, sound, radio frequency energy, magnetism, and the like. In the embodiment depicted, upon the introduction of photonic energy  132 , an electron  134  is caused to flow within the DNA strand  72  and flows to the lower potential transceivor  83 , which it causes to emit energy in the form of a photon and causes it to fluoresce. The fluorescence may be detected by a photodector  136  which, depending upon the intensity and frequency of the fluorescence, will monitor and measure activity within DNA strand  72 .  
         [0067]    [0067]FIG. 4 is a flow diagram of a process for imaging chromosomal events in biological systems. In the first step of the process depicted in FIG. 4, in step  160 , a neutron stream is produced by conventional means such as, e.g., a cyclotron. See, e.g., U.S. Pat. Nos. 5,699,394, 5,386,114, 4,853,550, 4,701,792, 4,176,093, and the like; the entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.  
         [0068]    Thereafter in  162  of the process, the flow of the neutron stream is regulated by means of, e.g., supercooled fluid. See, e.g., U.S. Pat. Nos. 5,872,826, 5,610,956, 5,367,547, 5,174,945, 5,128,097, and the like. The entire description of each of these United States patents is hereby incorporated by reference into this specification.  
         [0069]    In step  164  of the process, the slowed neutron stream is focused onto a nucleus of a cell which one wishes to scan. See, e.g., U.S. Pat. Nos. 6,054,708, 5,658,273, 5,076,993, etc., the entire disclosure of each of which is hereby incorporated by reference in to this specification. In this step  164 , the cell nucleus is bombarded with the slowed neutron stream, which is preferably focused onto desired target chromosomes.  
         [0070]    In one embodiment, streams of neutrons are simultaneously focused on different portions of the nucleus to produce a three-dimensional image. In this embodiment, one may scan the beams over the portions of the nuclei being examined to produce a real time image.  
         [0071]    The neutrons impacting the cell nuclei are transmitted and deflected. In step  166 , these deflected neutron beams are measured. The extent of the transmission and deflection of the neutron beam, and the intensity of each, varies with the mass contacted by the neutron beam. Thus, one can determine deflection patters of neutron beams for standardized DNA samples and compare this data with the deflection patterns produced with any particular DNA sample. This data correlation will indicate whether any particular DNA is aberrant, and/or is undergoing an event such as replication or transcription.  
         [0072]    The transmitted and/or deflected neutron beams are anaylzed in a controller comprised of a neutron detector, a monitor, image processing software, so that the shape, structure, motion, configuration, and relative positioning of the chromosomal moieties within the nuclei may be viewed and evaluated. By way of illustration and not limitation, one may thus examine, evaluate, and quantify phenomena such as the positioning of the histones and nucleosomes within chromatin, the spatial relationship between chromosomes, looping of the DNA, psuedo knot formation within the DNA, supercoiling within the DNA, unwinding of the DNA, the energy state of the DNA, and any other structural property normally or abnormally exhibited by chromatin. The observation, evaluation, and compilation of these properties allow one to prepare a database of normal and aberrant states of the cell.  
         [0073]    In step  168 , steps  160 ,  162 ,  164 , and  166  are repeated as the focus of the neutron beam is changed. Thus, one can scan a DNA segment in real time and instantaneously generate data indicate its condition and what events, if any, it is undergoing.  
         [0074]    The steps  160  through  168  can be repeated with a wide variety of standardized DNA samples, and test DNA samples, to produce a database that can thereafter be correlated with any particular set of readings. By way of illustration, such a database will have data regarding the phenotypes of individuals with specific maladies, such as disease state, age, etc. When a scanning of any particular DNA sample matches such a malady phenotype, one then gains an indicium of the possibility of such malady existing or developing.  
         [0075]    In practicing the techniques described in this specification, one may use procedures described in prior art patents. Thus, one should refer to U.S. Pat. No. 5,612,468 (Pteridine nuleotide analogs as fluorescent DNA probes),U.S. Pat. No. 5,846,708 (Optical and electrical methods and apparatus for molecule detection), U.S. Pat. Nos. 4,447,546, 4,582,809, 4,909,990, 5,776,672 (Gene detection niethod), U.S. Pat. No. 6,146,593 (High density array fabrication and readout method for fiber optic biosensor), U.S. Pat. No. 6,146,593, etc. The entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.  
         [0076]    As indicated elsewhere in this specification, the transceivors  59  (see FIG. 3A) are preferably nanotubes. As used this specification, the term nanotube includes a nanoparticle, which can be fabricated from gold, from carbon, from other materials, and may be fabricated in substantially any shape.  
         [0077]    In one embodiment, the nanoparticle consists essentially of gold. In another embodiment, the nanoparticle is a nanotube which can contain a single wall, or a double wall, or a multiplicity of walls. These walled nanotubes are well known to those skilled in the art. See, e.g., U.S. Pat. Nos. 6,187,760, 6,187,823, 6,183,174, 6,159,742, and the like. The entire disclosure of each of these United States patents is hereby incorporated by reference into this specification.  
         [0078]    The invention has been described by reference to deoxyribose nucleic acid structures, as well as ribonucleic acid structures. It is equally applicable to protein structures, to which an antibody may be bonded in conventional manner to different moieties on the protein entity.  
         [0079]    It is to be understood that the aforementioned description is illustrative only and that changes can be made in the apparatus, in the ingredients and their proportions, and in the sequence of combinations and process steps, as well as in other aspects of the invention discussed herein, without departing from the scope of the invention as defined in the following claims.