A Method of Selectively Masking One or More Sites on a Surface and a Method of Synthesising an Array of Molecules

• US 20160184788A1
• Filed: 08/15/2014
• Published: 06/30/2016
• Est. Priority Date: 08/16/2013
• Status: Active Grant

• Current Assignee: Evonetix Limited
• Original Assignee: Evonetix Limited
• Inventors: Jordan, Christopher John Favero, Hall, Daniel Arthur
• Granted Patent: US 10,195,580 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00427 using masks
• CPC Class Codes: B01J 2219/00441 using lasers
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00716 Heat activated synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C40B 50/18 using a particular method of attachment to the solid support
• CPC Class Codes: C40B 60/14 for creating libraries

Abstract

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 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 semi-conductor chip that uses micro-heaters to modulate a masking layer on areas of the chip surface.

Claims

1-93. -93. (canceled)

94. A method for creating a mask on a surface of a substrate to mask selected functionalised sites on the surface, the surface including a plurality of sites, wherein the substrate includes a plurality of spaced heating elements at respective sites on the surface, the heating elements being disposed on or proximal to the surface, the plurality of sites being functionalised to possess a functional property that is absent from the surface between the sites;

the method comprising;

applying, using a selectively operable dispenser, a layer of masking material onto the surface to cover the plurality of sites;

selectively applying, using a heating controller, an energy through the heating elements at each site to melt and adhere the masking material to the surface at selected sites, whereby the applied energy brings about a phase change in the masking material at the selected sites, and forming a non-porous layer to mask the selected sites; and

treating at least one non-selected site in the plurality of sites.

95. The method according to claim 94, wherein the functional property permits the site to react with at least one of the following:

an extrinsic agent, a substance, a material, and any combination thereof.

96. The method according to claim 95, wherein each functionalised site is derivatised with a surface-bound molecular precursor.

97. The method according to claim 94, wherein said masking material includes a waxy non-polar organic substance having a melting point in the range of approximately 10°

C. to approximately 75°

C.

98. The method according to claim 94, wherein the heating element at each site comprises a micro-heater.

99. The method according to claim 94, wherein the application of energy to the selected sites is controlled by a computer.

100. The method according to claim 94, wherein the masking material is applied to the surface in a first removable phase and the applied energy brings about a phase change in the masking material at the selected sites such that it adheres to the surface for masking the selected sites.

101. The method according to claim 94, wherein said masking material is applied to the surface in a particulate form, and the applied energy causes the particles to melt and coalesce.

102. The method according to claim 94, wherein the applied energy brings about the phase change in the masking material at the selected sites without increasing a temperature of the masking material at the selected sites.

103. The method according to claim 94, further comprising:

(a) providing a surface defining an array of sites, wherein each site includes a heating element;

(b) depositing a layer of masking material in a first removable phase on the surface to cover the plurality of the sites;

(c) applying thermal energy to the masking material at one or more selected ones, but not all, of the plurality of sites to cause or allow the masking material to undergo a first localised phase change to a second phase at said selected sites; and

(d) removing the remainder of the masking material in the first phase from the surface.

104. The method according to claim 96, wherein the treating includes treating the at least one non-selected site with at least one extrinsic reagent to produce at least one synthesized molecule.

105. The method according to claim 104, wherein the treating includes

reacting the surface-bound molecular precursor at at least one non-selected site with an extrinsic molecular chain extender to extend the surface-bound molecular precursor, wherein the surface-bound molecular precursor includes a reactive chemical moiety.

106. The method according to claim 105, wherein the surface-bound molecular precursor is a surface-bound oligonucleotide including a protected free terminal reactive group, and the molecular chain extender including a nucleosidic chain extender having a first unprotected reactive group capable of reacting with the protected free terminal reactive group of the surface-bound molecular precursor and a second protected reactive group;

the reacting including

de-protecting the surface-bound oligonucleotide; and

reacting the surface-bound oligonucleotide with the nucleosidic chain extender to extend the surface-bound oligonucleotide at at least one non-selected site.

107. The method according to claim 106, further comprising

removing the masking material from the surface after completion of the reacting of the surface-bound oligonucleotide with the nucleosidic chain extender;

re-masking the at least one selected site in the plurality of sites on the surface;

de-protecting the free terminal reactive group on the surface-bound oligonucleotide at at least one non-selected site; and

repeating the reacting of the surface-bound oligonucleotide with the nucleosidic chain extender using at least one of the nucleosidic chain extender and another nucleosidic chain extender

repeating the treating to obtain at least one synthetic oligonucleotide having a desired sequence.

108. An apparatus for selectively masking one or more sites on a surface of a substrate having a plurality of sites, the plurality of sites being functionalised to possess a functional property that is absent from the surface between the sites, the apparatus comprising:

a plurality of heating elements, a heating element being at each site in the plurality of sites;

a selectively operable dispenser for applying a layer of masking material onto the surface to cover the plurality of the sites; and

a heating controller for selectively applying an energy at each site through the heating elements to melt and adhere the masking material to the surface at selected sites to form a non-porous layer to mask the selected sites;

wherein at least one non-selected site in the plurality of sites is treated.

109. The apparatus according to claim 108, wherein the functional property permits the site to react with at least one of the following:

an extrinsic agent, a substance, a material, and any combination thereof.

110. The apparatus according to claim 108, wherein each functionalised site is derivatised with a surface-bound molecular precursor.

111. The apparatus according to claim 108, wherein each heating element comprises at least one of the following:

a micro-heater, a plate, a wafer of metal, another conductive material, and any combination thereof.

112. The apparatus according to claim 108, wherein said masking material includes a waxy non-polar organic substance having a melting point in the range of approximately 10°

C. to approximately 75°

C.

113. The apparatus according to claim 108, further comprising a computer and corresponding interfaces for controlling operation of the heating controller and the selectively operable dispenser.