Abstract: A method and a kit for separating double-stranded nucleic acid molecules from a mixture containing both single-stranded and double-stranded nucleic acid molecules. The method is particularly suitable for separating hybridized from unhybridized probe nucleic acid.

Abstract: A method for screening bacteria to select strains which inhibit the weed downy brome in small grain crops under field conditions and method for field application of the bacteria to inhibit downy brome in small grain crops in a commercial setting are described. Three Pseudomonas strains initially determined as non-fluorescent which passed the screen test are disclosed.

Abstract: A process for removing endotoxin from Gram-negative polysaccharides such as H. influenzae polyribosylribitol phosphate by mixing with a nonionic resin, a detergent and a chelating agent.

Abstract: Particles which enclose cavities can be produced by adding a water-insoluble solid, liquid or gaseous cavity generating compound to an aqueous solution of matrix material. Subsequent to forming particles by dispersion in a water-insoluble dispersion medium, the matrix is rendered insoluble in water by cooling, by covalent cross-linking or by polymerization. The cavity generating compound is washed out, whereafter the particles can be used as ion exchangers in gel filtration processes, in hydrophobic chromatography or in affinity chromatography, optionally subsequent to derivatizing the particles. The particles can also be used to advantage as microcarriers in the cultivation of anchorage-dependent cells.

Abstract: A gel contactor receives a fluid media produced in a bio-reactor and containing a product to be extracted, cells and other particles. The gel contactor has a cylindrical container with a cylindrical filter mounted inside the container. A freely rotatable wiper blade sweeps the upstream side of the filter in a closely spaced relationship. The container holds a supply of beads of an absorptive chromatography media such as an ion-exchange or affinity type gel, that selectively bond to the product. An orbital drive causes the blade, process fluid and gel to revolve. The rotation of the blade depolarizes the filter and circulates the process fluid process fluid and gel within the container so that they are well mixed, with substantially no dead spots. After mixing and filtration an elution buffer solution strips the product from the gel. There are no rotary seals connecting to the container.

Abstract: A solid phase binding member for the detection of an analyte in a test sample is described. The binding member comprises: (1) a solid support having micropores; (2) a polymer reversibly water-soluble before its application to the solid support; and (3) a ligand covalently attached to the polymer, the ligand interacting specifically with the analyte. The solid support can have micropores throughout or on its surface, and can be rayon, paper, fabric, plastic, agarose or polyacrylamide beads, glass, microcrystalline cellulose, or acid-treated plastic. The polymer can be carrageenan or sodium alginate. The ligand can be an antibody, a univalent antigen-binding fragment of an antibody, an antigen, a hapten, an enzyme, a hormone, or a single-stranded nucleic acid. Methods of use of the binding member are also described involving incorporation into a test device. The test device can be a dip stick, a hollow vessel, a slide, or a porous bead.

Abstract: Membrane separation of monosaccharides from an aqueous solution containing higher saccharides and saccharifying enzyme is considerably improved when the separation is performed under conditions where the polarization modulus for the enzyme is between 10 and 1,000, especially when the latter is between 50 and 500. A process utilizing this constraint affords a considerable savings in enzyme residence time and enzyme usage, and permits glucose of at least 94% purity to be prepared using membranes with a molecular weight cutoff as high as 70,000 with partial saccharification of thinned starch to give glucose levels in the range of 65-90%.

Abstract: A method of measuring chain breakage in the DNA of a eucaryotic cell is disclosed. This method includes (a) contacting the cell with a stripping solution that lyses and solubilizes the cell without denaturing its DNA, thereby forming a nucleoid having a halo, (b) measuring the width of the halo, and (c) determining the number of chain breaks from the measured width. The halo includes at least one loop of undenatured DNA, and has a width related to the number of DNA chain breaks in the loop. The cell to be examined may be adhered to a support prior to its contact with the stripping solution. The number of DNA chain breaks can be determined by compairing the measured width of the nucleoid halo with a reference value.

Abstract: Fast high resolution separations of biopolymers with retention of biological activity have been achieved by hydrophobic interaction chromatography using trialkoxy silyl ethers of the general formula(RO).sub.3 Si--(CH.sub.2).sub.m --O--(CH.sub.2 CH.sub.2 O).sub.n 13 (CH.sub.2).sub.p R'chemically bonded to silica-based chromatographic supports. In the formula R is alkyl of from one to five carbons, m is an integer from two to five, n is an integer from one to five, p is an integer from zero of ten, and R' is methyl, phenyl, or substituted phenyl. Stable and reproducible bonded phases are prepared in a novel solventless procedure by a bonding process which uses a defined and controlled amount of water on the silica surface and a gaseous or volatile basic catalyst such as ammonia to produce a controlled amount of silane polymerization and cross-linking in addition to extensive bonding between silane and silica.

Abstract: This invention relates to processive DNA polymerases and methods for using them.

Abstract: This invention relates to a novel method for assaying 1,5-anhydroglucitol, which is expected to serve as a marker for diabetes, and a kit therefor. More particularly, it relates to:(1) a method for assaying 1,5-anhydroglucitol, which comprises selectively removing sugars from a specimen containing 1,5-anhydroglucitol; allowing pyranose oxidase or L-sorbose oxidase to act on 1,5-anhydroglucitol contained in the sample thus obtained in the presence of oxygen; and determining 1,5-anhydroglucitol from the amount of the hydrogen peroxide thus formed; and(2) a reagent kit for assaying 1,5-anhydroglucitol which comprises an agent for removing sugars, a reagent for detecting hydrogen peroxide and an enzyme for oxidizing 1,5-anhydroglucitol.

Abstract: 2-Keto-L-gulonic acid is separated from a fermented medium containing the calcium salt of 2-keto-L-gulonic acid, by carrying out the following operations: separation of insolubles; removal of inorganic cations; and separation of the 2-keto-L-gulonic acid.

Abstract: A new method for releasing sample nucleic acids from cells, bacteria and viruses comprises non-invasively sonicating the sample contained within a sample container brought into physical contact with the vibrating element of a sonicator tuned to resonate at a frequency of 40 KHz or greater.

Abstract: A method is disclosed for the analysis of gene expression in human biopsy that is useful in the diagnosis and prognosis of disease and evaluation of risk for disease. The method comprises the steps of compiling data regarding the level of expression of certain individual cloned gene sequences from patients having defined pathological conditions and from normal patients and thereafter identifying sequences that characterize the pathological condition.The data regarding the expression of the individual cloned genes are stored in a defined pattern or array. Replicas of this array are hybridized to radioactive probes made using the RNA isolated from biopsy tissue. The extent of hybridization of the probe to each of the cloned sequences is proportional to the level of expression of the cloned sequence in the tissue from which the probe was made. This may be done by exposing the hybridized clones to x-ray film and scanning the x-ray films to quantify the cloned sequences.

Abstract: Disclosed is a process and device for fusing cells in which the cells are doped with magnetic particles and exposed to a nonhomogeneous magnetic field which permeates the fusion space in such a way that the doped cells collect close together, and then, in order to create the disruptions in the membrane structures of the adjacent cells, the cells are exposed either to the pulse of an electric field of at least the level of the breakdown voltage or to chemicals which cause the disruptions in the membrane structure such as polyethylene glycol, or to inactivated viruses which cause the disruptions in the membrane structure such as Sendai viruses.

Abstract: Hydrated sodium silicate particles can be expanded by heat to form thin-walled bubbles that can be broken, neutralized, washed and dried to provide hydrated silica flakes. These flakes can be mixed with non-swelling sorptive particles such as TLC grade silica and used to make chromatographic articles. One such article is a composite of a poly(tetrafluoroethylene) fibril matrix in which those particles and hydrated or fired silica flakes are enmeshed. The hydrated silica flakes can be fired to a refractory state and then incorporated into protective coatings to enhance their resistance to abrasion while also better protecting the coated substrates from corrosion.

Abstract: A process for determining the presence of a particular nucleic acid sequence in a test sample comprising(a) chemically modifying nucleic acids in the test sample either to introduce a label or a reactive site in a manner that supports their hybridizability,(b) contacting under hybridization conditions the chemically modified sample nucleic acids with a hybridizable nucleic acid probe which either, when the sample nucleic acids have been modified to introduce a label, carrys a reactive site or, when the sample nucleic acids have been modified to introduce a reactive site, is labeled,(c) contacting the solution resulting from step (b) with a immobilized form of a reactive partner to the reactive site to form a stable bond with the reactive site on the sample nucleic acids or the probe, respectively,(d) separating the resulting immobilized fraction from the remaining solution, and(e) determining the presence of the label in the separated immobilized fraction or a decrease in the label in the remaining solution.

Abstract: A process for the isolation and separation of lysozyme and avidin from egg white is carried out by:step (a) contacting egg white with a weakly acidic cation exchange resin whereby lysozyme and avidin are adsorbed on to the resin; separating the resin from the egg white and washing the resin to remove residual egg white therefrom; and contacting the washed resin with a low ionic strength eluting buffer whereby lysozyme is eluted from the resin while avidin remains adsorbed on the resin; andstep (b) repeating the complete procedure defined in step (a) for two or more times; andstep (c) finally contacting the resin containing accumulated adsorbed avidin with a high ionic strength eluting buffer whereby avidin is eluted from the resin.Lysozyme and avidin are both commercial products useful, for example, in pharmaceutical applications.

Abstract: Recombinant DNA transfer vectors containing DNA inserts which are complementary to either the human LDL receptor gene, or its mRNA transcript, are disclosed. Also disclosed are methods which utilize these genetic probes for diagnosing Familial Hypercholesterolemia (FH) in a suspected individual. A case study of numerous such individual are disclosed wherein the genetic deletion mutation is detailed with great precision through the practice of this invention.

Abstract: This invention pertains to an improved process for the preparation of gamma-irone by bioconversion comprising treating an iris rhizome substrate selected from the group consisting of iris rhizomes, iris rhizome parts, iris rhizome extracts, iris rhizome extraction wastes, plant cell cultures of iris rhizomes, and mixtures thereof, with a bacteria selected from the genera group consisting of Enterobacteriacea, Pseudomonacea, the active enzyme fractions of such bacteria, and mixtures thereof, in the presence of a plant cell culture medium.

Abstract: A method for sequencing a strand of DNA, including the steps of: providing the strand of DNA; annealing the strand with a primer able to hybridize to the strand to give an annealed mixture; incubating the mixture with a deoxyribonucleoside triphosphate, a DNA polymerase, and a chain terminating agent under conditions in which the polymerase causes the primer to be elongated to form a series of DNA products differing in length of the elongated primer, each DNA product having a chain terminating agent at its elongated end; the number of each DNA product being approximately the same for substantially all DNA products differing in length from 1 to 20 bases.

Abstract: Gas containing granules of a resiliently compressible material having a density variable with pressure are used as a solid phase support in liquid phase reactions such in immunological reactions. Varying pressure causes the density of the granules to change and is used for mixing and separating the granules in liquid phase. In an immunological reaction, the granules having an attached antibody are combined with a solution containing an antigen, then varying pressure is applied to the solution to mix the granules in the solution to fix the antigen to the antibody and then pressure on the solution is varied to force the granules to the top or bottom of the solution whereby the solution can be separated from the granules.

Abstract: Determination of microorganisms in body fluids for diagnosis is carried out by passing a body fluid through a column packed with a sorbent which traps microorganisms contained by the body fluid. A culture medium is added to the column, and after culturing the presence of microorganisms is determined. The column is a substantially cylindrical body and is connected via a porous partition to a conical terminal at each end. One conical terminal is an inlet and the other is an outlet. A sorbent porous material is positioned between the partitions and the partitions have different porosities. Total inner volume of the column is about 30 to 300 ml, and volume ratio of the cylindrical body to the conic terminals is about 1:0.3 to 1:5. Preferably, the volume of the cylindrical body is about 10 to 100 ml and the total volume of the both conic terminals is about 20 to 200 ml.

Abstract: A process for the purification of alcohol oxidase from whole cells of Pichia pastoris grown on methanol by the sequential steps of autolysis, crossflow filtration, ultrafiltration and recrystallization.

Abstract: A bioaffinity separation method is provided along with a solid affinity support utilized in that method. Additionally, immobilized enzyme systems are provided for use as enzyme electrode systems. The support is based on an inert perfluorocarbon polymer carrier with ligands or binders attached to its surface through a highly fluorinated isocyanate anchor group. Methods for preparing such supports and their use in capturing target molecules from samples and in analytical applications are also provided.

Abstract: A method for detecting and localizing single base substitutions in RNA or DNA that involves RNAase A cleavage of single base mismatches in RNA:RNA or RNA:DNA heteroduplexes. A RNA probe complementary to wild type DNA is annealed to the test DNA containing a single base substitution. Many of the possible single base mismatches can be cleaved by RNAase A. The location of the single base substitution can be determined by analyzing the sizes of the RNA cleavage products.

Abstract: This invention features vectors and a method for sequencing DNA. The method includes the steps of:(a) ligating the DNA into a vector comprising a tag sequence, the tag sequence includes at least 15 bases, wherein the tag sequence will not hybridize to the DNA under stringent hybridization conditions and is unique in the vector, to form a hybrid vector,(b) treating the hybrid vector in a plurality of vessels to produce fragments comprising the tag sequence, wherein the fragments differ in length and terminate at a fixed known base or bases, wherein the fixed known base or bases differs in each vessel,(c) separating the fragments from each vessel according to their size,(d) hybridizing the fragments with an oligonucleotide able to hybridize specifically with the tag sequence, and(e) detecting the pattern of hybridization of the tag sequence, wherein the pattern reflects the nucleotide sequence of the DNA.

Abstract: Fragments of a biopsy sample on the order of about 50 to 5000 cells are preferred for establishing viable tumor cell cultures for purposes such as establishing cell lines, chemotherapeutic assays and the like. Such fragments retain the three-dimensional cellular structure or organization of the original tumor and, therefore, can be cultured more readily. To obtain such fragments suitable for culturing, the biopsy sample can be enzymatically digested in a proteolytic or nucleolytic enzyme, such as collagenase, or by mechanical dissociation, or both where necessary. The fragments can then be suspended in an aqueous medium so that non-aggregated cells (e.g., red blood cells, lymphocytes, macrophages) and cellular debris will form a supernatant while the remaining fragments containing aggregated tumor cells are deposited in a sediment layer.

Abstract: The method of this invention is applicable to rapid separation, isolation, and purification of DNA or RNA from biological samples. The DNA/RNA may be in double-stranded or single-stranded form. The method is particularly advantageous for resolving genetic DNA or RNA found in bacteria, virus, and mammalian cells, and for use with samples of human bodily fluids and tissues, including stool, sputum, urine, and blood samples. DNA or RNA can be separated effectively from interfering components, particularly proteins, biological pigments and mucopolysaccharides. The method of the present invention can utilize commercially available strong or weak anion exchanger materials with selected solutions of known ionic strength for adsorption and elution.

Abstract: A process for the specific adsorption of heparin and other heparin-like substances which comprises flowing a buffered solution of whole blood, from which corpuscular blood constituents have been removed, plasma and/or solutions containing whole blood or plasma through an adsorber capsule containing a medium that adsorbs heparin and other heparin-like substances at an acid pH, preferably in the range of 4.0 to 5.5. Preferably, the process is carried out in a closed, extracorporeal circulation and the medium possesses anion exchange resin properties.

Abstract: Oligonucleotide probes reactive with regions of neu oncogenes of mammalian origin in which the mutation causing activation of such oncogenes is contained are described, as are methods for their use in detecting the presence of neu oncogenes in tumor cells. Antibodies specific for gene products encoded by neu oncogenes are also described.

Abstract: A method for carrying out a nucleic acid hybridization test to detect a target nucleic acid sequence, the method including the steps of(1) providing a polymer molecule bonded to a first single-stranded nucleic acid sequence which is either (a) a first probe capable of hybridizing to the target nucleic acid sequence, or (b) a second nucleic acid sequence capable of hybridizing to a third nucleic acid sequence bonded to a first probe capable of hybridizing to the target nucleic acid sequence; provided that, where the polymer molecule comprises DNA, the DNA is of heterogeneous base sequence;(2) where the polymer used in step (1) is bonded to (b), providing the first probe bonded to the third nucleic acid sequence;(3) denaturing the target nucleic acid sequence;(4) contacting the denatured target nucleic acid sequence with the polymer molecule bonded to the first single-stranded nucleic acid sequence and, if the first nucleic acid sequence is (b), to the first probe bonded to the third nucleic acid sequence; and(

Abstract: A method is provided for isolating DNA from eukaryotic cell and flow sorted chromosomes. When DNA is removed from chromosome and cell structure, detergent and proteolytic digestion products remain with the DNA. These products can be removed with organic extraction, but the process steps associated with organic extraction reduce the size of DNA fragments available for experimental use. The present process removes the waste products by dialyzing a solution containing the DNA against a solution containing polyethylene glycol (PEG). The waste products dialyze into the PEG leaving isolated DNA. The remaining DNA has been prepared with fragments containing more than 160 kb. The isolated DNA has been used in conventional protocols without affect on the protocol.

Abstract: A system for continuous production and removal of a biological substance from a dispersed cell culture. The system comprises a reactor adapted to maintain the cell culture under incubating conditions and means for pumping limited volumes of the culture fluid from the reactor and through an external substance separation device adapted to extract the substance in a limited time on a continuous basis without collection of, or damage to, the dispersed cells. Less than 5% of the total culture fluid volume is outside the reactor (Volume outside or Vo) at any time and a given dispersed cell is outside the protective environment of the reactor for less than about two minutes, as expressed by the following relationship, ##EQU1## In preferred embodiments the external device comprises a plurality of substance-extracting, porous, hollow fibers through which the culture fluid, substance, and dispersed cells are continuously passed.

Abstract: An improved hollow fiber bioreactor system is disclosed that includes an arrangement for removing the plasticizer that is typically found within the hollow fibers of hollow fiber cartridges so as to prevent this material from contaminating the nutrient fluid. The plasticizer is removed without jeopardizing sterility of the bioreactor.

Abstract: A specific high molecular weight antigen (gp650) is detected in the sera of cancer patients with gastrointestinal cancer, cancer of the liver, breast cancer, cancer of the lung, cancer of the tongue, fallopian cancer, lymphoma and multiple myeloma. A monoclonal antibody specific for the 650 kD high molecular weight glycoprotein antigen has been harvested from mouse ascites and culture supernatants and used for the detection of antigen in cancer patient sera. Disclosed are (1) the method for preparing the antigen, (2) the properties of the antigen, (3) the method for preparation of the monoclonal antibody, (4) the characteristics and specificity of the monoclonal antibody and (5) a diagnostic kit based upon the specific monoclonal antibody.

Abstract: A method and device are provided for separating magnetized particles from biological fluids. Cells such as cancer cells coated with magnetized particles can be separated from uncoated healthy cells. A fluid mixture of cancer cells, healthy cells and magnetizable particles is introduced into a container such as a disposable blood bag which is attached in a cassette on an underlying plane magnetic plane that provides a magnetic field. Incubation is carried out during which the cancer cells become coated with the magnetizable particles. The magnetic field pulls the coated cells down towards the bottom of the bag and anchors them, and uncoated healthy cells are removed from the bag. The separated uncoated healthy cells may be advanced through a final separation unit where any loose magnetizable particles are removed. There is provided means for adjusting vertical distance between the cassette and the magnetic plane and for agitating fluid within the container attached to the cassette.

Abstract: This invention provides methods for the detection of a target genetic material having a desired base sequence or gene. Also disclosed are methods for the detection of mutations. Also provided are components for use in such methods.The methods are based upon techniques which utilize two labeled single stranded polynucleotide segments which are complementary to the same or the opposite strands of the target genetic material. The methods of the invention result in the formation of a double hybrid and/or multihybrid.

Abstract: In accordance with the practices of this invention, there is provided a heterologous detection system and components useful in conjunction therewith and kits for carrying out the heterologous detection system. The heterologous detection system employs a heterologous entity and a signalling entity. The heterologous entity contains two free complex forming sites that form different complexes, i.e., two kinds of complexes can be formed. The first free complex forming site is utilized to recognize the labeled probe and the second free complex forming site is utilized to recognize the signalling entity, with each complex formed being different. The signalling entity contains a free complex forming site that can recognize the second free complex forming site of the heterologous entity and a signalling portion that is capable of generating a signal.

Abstract: A stable, single-stranded nucleoprotein filament adapted to complex specifically and stably with a target duplex DNA having a selected base sequence. The filament is composed of a single-stranded DNA probe having a region of homology with the target base sequence, and RecA protein bound stably to the DNA probe by adenosine 5'-(.gamma.-thio)triphosphate. The filament is useful in a novel system and method for enriching target duplex DNA which contains a region homologous to the probe sequence, for blocking selected restriction endonuclease sites in the target DNA, and in other DNA methodologies in which stable rapid triple-strand synaptic formation in duplex DNA can be exploited.

Abstract: Improved method for the purification of LPF-HA (Leucocytosis promoting far hemagglutinin) on industrial scale which comprises contacting a LPF-HA-containing solution from culture media of Bordetella pertussis with a cellulose sulfate gel, a crosslinked polysaccharide sulfate gel, or a polysaccharide gel chemically bound with dextran sulfate, thereby adsorbing LPF-HA on the gel, and then eluting LPF-HA from the gel. Said method can give a highly purified LPF-HA which does not contain any other proteins, lipid, saccharides, etc. and further undesirable endotoxin, and hence can be used for producing various reagents, medicines and pertussis vaccine.

Abstract: The invention provides a method for diagnosis of genetic abnormalities or other genetic conditions which can be readily automated. The method is used to determine the presence or absence of a target sequence in a sample of denatured nucleic acid and entails hybridizing the sample with a probe complementary to a diagnostic portion of the target sequence (the diagnostic probe), and with a probe complementary to a nucleotide sequence contiguous with the diagnostic portion (the contiguous probe), under conditions wherein the diagnostic probe remains bound substantially only to the sample nucleic acid containing the target sequence. The diagnostic probe and contiguous probe are then covalently attached to yield a target probe which is complementary to the target sequence, and the probes which are not attached are removed.

Abstract: An amplified hybridization assay is described in which a family of signal-generating secondary probes bind to a primary probe that hybridizes to the target sequence of interest. Thus, an enormously amplified signal is generated by the hybridization event. The assay can be used for a variety of laboratory and clinical purposes and is automatable.

Abstract: This invention relates to a new protein L and subfragments thereof with binding activity for all classes of immunoglobulins from different species, a process for preparing the same, a reagent kit, a pharmaceutical composition and strain 312 of P. magnus. The process for preparing the protein and subfragments thereof is characterized in that the microorganism P. magnus 312 is treated with proteolytic enzymes or mutanolysin.

Abstract: A cationic detergent having a positively charged group and a hydrophobic group is used to conjugate an enzymatically active enzyme molecule with a single-stranded nucleic acid molecule. The conjugate may be used to detect the presence of nucleic acid molecules having a nucleotide sequence which is complementary to that of the single-stranded molecule of the conjugate.

Abstract: Molecules complementary to nucleotide sequences encoding mutant ras protiens which contain a single-base mutation in the codon encoding amino acids at position 13, 12 or 61 have been produced. These molecules are useful in methods of detecting specific single-base mutations in altered ras genes and the specific cancers associated with such mutations.

Abstract: A process for purifying lysocellin which comprises mixing lysocellin solids with sufficient halogen acid to convert fatty acid ester salt impurities into water-soluble metal halogen salts and water-insoluble free fatty acids and to convert lysocellin salts into water-soluble metal halogen salts and water-insoluble lysocellin acid, separating the halogen salts from the lysocellin acid and fatty acid solids, mixing the lysocellin acid and fatty acid solids with sufficient caustic reagent to convert free fatty acids into water-soluble alkali metal salts and to convert lysocellin acid into a water-insoluble alkali metal lysocellin salts, and separating the water-soluble fatty acid alkali metal salts from the alkali metal lysocellin solids.

Abstract: A method is disclosed to detect the presence of an analyte. The method involves forming a complex comprising the analyte and a binding entity. The binding entity comprises a first partner of an energy transfer system. The complex is then contacted with a reporting entity to form a unit. The reporting entity comprises a second partner of the energy transfer system. The first partner and the second partner are within Furster's radius of each other in the formed unit. The unit is irradiated with energy which can only be absorbed by one of said partners, namely, the energy donor, which then emits fluorescent energy. Some of this energy is absorbed by the other of said partners, namely, the energy acceptor, which also emits fluorescent energy. However, the fluorescent energy of the energy acceptor is of longer wavelength and in addition may be of substantially greater duration than the fluorescent energy of the energy donor.

Abstract: A colored compound containing a cationic group and a cellulose reactive group, especially a compound of the formula:A--Y--B IY'--B IIwhereinA is the cationic group;Y is a chromophore;Y' is a cationic chromophoreandB is the reactive group, which is suitable for the preparation of a protein adsorbent or precipitant for use in the separation of mixtures of proteins.

Abstract: A first mixture is prepared that contains labeled chain fragments which each has a common end adjacent to a primary nucleotide and a termination at a position from the primary through an nth nucleotide, the first mixture containing nucleotide chain fragments of each length from termination at the primary through termination of the nth nucleotide. A second mixture is prepared that contains labeled chain fragments beginning at the common end and terminating at positions from the first through the nth nucleotide, the second mixture containing chain fragments of each length terminating wherever either a first or a second of the four nucleotides occurs. A third mixture is prepared that contains labeled chain fragments beginning at the common end and terminating at a position from the first through the nth nucleotide, the third mixture containing chain fragments of each length terminating wherever the first or a third of the four nucleotide sequences occurs.