A method is provided for detecting a hybridisation indication indicative of an amount of hybridisation between a set of probe biomolecules provided at a reaction site and a set of sample biomolecules. The method includes supplying the set of sample biomolecules to the reaction site comprising the set of probe biomolecules. The reaction site is heated to cause dissociation of probe/sample-biomolecule-pairs previously hybridized when the set of sample biomolecules were provided to the reaction site. The hybridisation indication is generated based on detecting the dissociation of the probe/sample-biomolecule pairs caused by heating the reaction site.
A reaction duration is controlled for a reaction performed on biomolecule samples on an apparatus comprising temperature control circuitry to independently control temperature for respective reaction sites. A higher temperature is applied to a first subset of reaction sites and a lower temperature is applied to a second subset of reaction sites. The reaction is started at a first time and ended at a second time when the reaction duration has elapsed since the first time. The reaction duration is selected depending on an analysis of dependence of an error rate on the reaction duration, the error rate comprising a rate of errors caused by an unreacted fraction of biomolecule samples at the first subset of reaction sites that remain unreacted at the second time and a reacted fraction of biomolecule samples at the second subset of reaction sites that have already reacted at the second time.
Data storage is provided using double-stranded nucleic acid molecules (70) provided on a thermal control device (52) comprising a plurality of sites (54) and temperature control circuitry (56) to independently control a temperature of each of the plurality of sites. The temperature control circuitry (56), controls the site temperatures to provide a different temperature at a target site compared to other sites of the plurality of sites. The different temperatures at the target site and the other sites provide a greater probability of a read or write operation acting on the target site compared to the other sites. The temperature-based addressing helps to increase physical storage density.
The present invention relates to methods for the high fidelity synthesis of oligonucleotides and polynucleotides on a solid surface. In particular, the invention relates to methods of synthesising oligonucleotides, polynucleotides, and doublestranded polynucleotides/nucleic acids, such as DNA and XNA, wherein the process comprises thermally controlled deprotection steps at the 5'-OH of previously coupled nucleosides or nucleotides at selected sites on the surface of the substrate.
C07H 1/00 - Processes for the preparation of sugar derivatives
C07H 19/073 - Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07H 23/00 - Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
C40B 10/00 - Directed molecular evolution of macromolecules, e.g. RNA, DNA or proteins
6.
ERROR DETECTION DURING HYBRIDISATION OF TARGET DOUBLE-STRANDED NUCLEIC ACID
FEEE comprise at least one erroneous hybridised fragment, and discarding at least part of the erroneous fragment to exclude it from a subsequent further hybridisation step. By detecting and removing erroneous fragments throughout a staged and controlled hybridisation process, erroneous fragments are prevented from diluting the pool of error-free fragments at each hybridisation step, to improve yield.
The present invention relates to chemical linkers and protecting groups, compounds and compositions containing the chemical linkers or protecting groups, and intermediates and processes that can be used to prepare them. The chemical linkers and protecting groups are based on pyrrolidine and piperidine activating groups, which undergo intramolecular cyclisation upon heating with release of carbon dioxide, thereby releasing the organic compound from a substrate. In particular, those chemical linkers and protecting groups are useful in the solid phase synthesis of oligonucleotides according to the following representative schemes.
C07D 207/09 - Radicals substituted by nitrogen atoms not forming part of a nitro radical
C07D 211/26 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
C07H 1/00 - Processes for the preparation of sugar derivatives
C07H 19/073 - Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
C07H 19/173 - Purine radicals with 2-deoxyribosyl as the saccharide radical
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07H 23/00 - Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12
8.
METHOD FOR PRODUCING DOUBLE STRANDED POLYNUCLEOTIDES BASED ON OLIGONUCLEOTIDES WITH SELECTED AND DIFFERENT MELTING TEMPERATURES
A method for identifying a group of single-stranded oligonucleotides for self-assembly into a double-stranded polynucleotide, the group comprising a plurality of overlapping complementary oligonucleotides, wherein each overlap between complementary oligonucleotides is selected to have a melting temperature (Tm) that differs from the melting temperatures of all other overlapping complementary oligonucleotides in the group.
A temperature control device (2) comprises a number of active thermal sites (6) disposed at respective locations on a substrate (10), each comprising a heating element (13) for applying a variable amount of heat to a corresponding site of a medium and a thermal insulation layer (16) disposed between the heating element and the substrate. At least one passive thermal region (8) is disposed between the active thermal sites (6) on the substrate (10), each passive thermal region (8) comprising a thermal conduction layer (18) for conducting heat from a corresponding portion of the medium to the substrate (10). The thermal conduction layer (18) has a lower thermal resistance in a direction perpendicular to a plane of the substrate (10) than the thermal insulation layer (16). This enables precise control over both heating and cooling of individual sites in a flowing fluid, for example.
A technique for measuring the resistance of a resistive element (4) in the presence of a series diode (10) is provided. By supplying three different currents I1, l2, l3 and measuring corresponding voltages V1, V2, V3 across the resistive element (4) and diode (10), the voltages can be combined to at least partially eliminate an error in the measured resistance of the resistive element (4) caused by a voltage drop across the diode (10). A technique for current control in an array of resistive elements (60) is also described in which a column of resistive elements (60) is provided with two or more current sources (70, 72) switched so that while one current source (70) is providing current to the column line (66) corresponding to a selected resistive element (60), another current source (72) has its amount of current adjusted.
G01R 1/20 - Modifications of basic electric elements for use in electric measuring instrumentsStructural combinations of such elements with such instruments
G01K 17/16 - Indicating product of flow and temperature difference directly using electrical means for both measurements
A controller for a thermo-electric cooler is disclosed. The controller comprises a current source for providing current for driving the thermo-electric cooler and a plurality of voltage supply connections for providing a plurality of different voltages for driving current controlled by the current source through the thermo-electric cooler. Voltage selection circuitry is provided for selecting a voltage from the plurality of different voltages, when connected, and for applying the voltage selected to the thermo-electric cooler. When selecting the voltage from the plurality of different voltages, the voltage selection circuitry is configured to select the voltage that, when compared to the other voltages of the plurality of voltages, minimises a potential difference across the current source.
F25B 21/00 - Machines, plants or systems, using electric or magnetic effects
F25B 21/02 - Machines, plants or systems, using electric or magnetic effects using Peltier effectMachines, plants or systems, using electric or magnetic effects using Nernst-Ettinghausen effect
12.
A METHOD OF SELECTIVELY MASKING ONE OR MORE SITES ON A SURFACE AND A METHOD OF SYNTHESISING AN ARRAY OF MOLECULES
A method of creating a mask on a surface of a substrate is disclosed. The substrate comprises a plurality of spaced heating elements on or proximal to the surface. The method comprises applying a layer of masking material to the surface and employing the heating elements to apply energy to the masking material at selected sites, whereby the applied energy brings about a phase change in the masking material at the selected sites such that it adheres to the surface or can be displaced from the surface to mask or unmask the selected sites respectively. A method of synthesising an array of molecules, an apparatus for selectively masking one or more sites on a surface and a semiconductor chip that uses micro-heaters to modulate a masking layer on areas of the chip surface.
B01J 19/00 - Chemical, physical or physico-chemical processes in generalTheir relevant apparatus
C40B 50/18 - Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creationParticular methods of cleavage from the solid support using a particular method of attachment to the solid support
C40B 60/14 - Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
patents
