Devices and Formulations

Abstract

Methods are described of delivering biological material, which methods include the steps of providing a liquid formulation containing the biological material, supplying the liquid formulation to an outlet and subjecting liquid issuing from the outlet to an electrical field thereby causing electrohydrodynamic processing of the liquid without denaturing the biological material. In one example, the liquid formulation is provided by removing salts from a formulation containing biological material that does not denature in alcohol and then adding an alcohol to the formulation before supplying the liquid formulation to the outlet. An acid may be added to the liquid formulation before supplying the liquid formulation to the outlet.

1 . A method of delivering biological material, which method comprises providing a liquid formulation containing the biological material, supplying the liquid formulation to an outlet and subjecting liquid issuing from the outlet to an electric field thereby causing electrohydrodynamic processing of the liquid without denaturing the biological material.  
     
     
         2 . A method of delivering biological material, which method comprises providing a liquid formulation containing the biological material, supplying the liquid formulation to an outlet and subjecting liquid issuing from the outlet to an electric field sufficient to cause comminution of the liquid to produce droplets containing the biological material without denaturing the biological material.  
     
     
         3 . A method according to  claim 1 , which comprises providing the liquid formulation by removing salts from a formulation containing biological material that does not denature in alcohol and then adding an alcohol to the formulation before supplying the liquid formulation to the outlet.  
     
     
         4 . A method according to  claim 3 , which further comprises adding an acid to the liquid formulation before supplying the liquid formulation to the outlet.  
     
     
         5 . A method according to  claim 4 , wherein the acid is acetic acid.  
     
     
         6 . A method according to  claim 3 , wherein the alcohol is ethanol or polyethylene glycol.  
     
     
         7 . A method according to  claim 1 , which comprises providing the liquid formulation by adding surfactant to a formulation containing the biological material before supplying the liquid formulation to the outlet.  
     
     
         8 . A method according to  claim 1 , which comprises providing the liquid formulation by adding polymer to a formulation containing the biological material before supplying the liquid formulation to the outlet.  
     
     
         9 . A method according to  claim 1 , which comprises providing the liquid formulation by adding surfactant and polymer to a formulation containing the biological material before supplying the liquid formulation to the outlet.  
     
     
         10 . A method of delivering biological material by processing a relatively highly conductive liquid such as an aqueous formulation containing the biological material, which method comprises adding polymer to the liquid, then supplying the polymer-containing liquid to an outlet and subjecting polymer containing liquid issuing from the outlet to an electric field sufficient to cause formation of a cone and j et.  
     
     
         11 . A method according to  claim 8 , wherein the polymer has a molecular weight of at least 40000.  
     
     
         12 . A method according to  claim 8 , wherein the polymer is selected from the group consisting of PVA, PVP, polyhyaluronate, polysucrose and other polysaccharides such as starch, cellulose and chitin and chemical derivatives thereof, Palaemon acids, modified collagen and derivatives thereof.  
     
     
         13 . A method according to  claim 8 , which comprises adding a polymer selected from 0.2 g/10 ml of PVP of molecular weight 360000; PVP with a molecular weight of 360000 at a concentration in the range 0.1-0.6 g/10 ml; PVA with a molecular weight of 125000 at a concentration in the range 0.1 to 0.7 g/10 ml of formulation; and PVA with a molecular weight of 125000 at a concentration of 10 mg per ml.  
     
     
         14 . (canceled)  
     
     
         15 . (canceled)  
     
     
         16 . (canceled)  
     
     
         17 . A method according to  claim 10 , which also comprises adding surfactant to the formulation.  
     
     
         18 . A method according to  claim 7 , which comprises adding as the surfactant a material selected from the group consisting of didodecyldimethylammonium bromide, benzalkonium chloride, Tween 20, Tween 80 and Brij 30.  
     
     
         19 . A method according to  claim 1 , wherein the electric field causes comminution of the liquid.  
     
     
         20 . A method according to  claim 8 , wherein the amount of polymer added is such that subjecting polymer containing liquid issuing from the outlet to the electric field causes formation of a fibre or fibrils.  
     
     
         21 . A method according to claims  1 , wherein the liquid contains biological material selected from the group consisting of DNA, DNA fragments, plasmids, RNA, proteins, peptides, hormones, lipids, enzymes and cytokines.  
     
     
         22 . A method of enabling electrohydrodyamic processing of an aqueous formulation containing biological material, which method comprises removing salts from the aqueous formulation, then adding an alcohol and an acid to the formulation prior to subjecting liquid issuing from an outlet to an electric field sufficient to cause formation of a cone and jet.  
     
     
         23 . A method according to  claim 22 , which comprises adding as the alcohol at least one of ethanol and polyethylene glycol.  
     
     
         24 . A method according to  claim 22 , which comprises adding as the acid as acetic acid.  
     
     
         25 . (canceled)  
     
     
         26 . A method according to  claim 21 , which comprises adding from 0.2 to 1 mM of acid in the acid adding step.  
     
     
         27 . (canceled)  
     
     
         28 . A method of enabling electrohydrodyamic processing of an aqueous formulation containing at least one of DNA, DNA fragments and plasmids, which method comprises removing salts from the aqueous formulation, then adding an ethanol and acetic acid to the formulation prior to subjecting liquid issuing from an outlet to an electric field sufficient to cause formation of a cone and jet.  
     
     
         29 . A method according to  claim 28 , which comprises adding ethanol to provide a formulation which is up to 90% by volume ethanol.  
     
     
         30 . (canceled)  
     
     
         31 . (canceled)  
     
     
         32 . (canceled)  
     
     
         33 . (canceled)  
     
     
         34 . (canceled)  
     
     
         35 . (canceled)  
     
     
         36 . (canceled)  
     
     
         37 . (canceled)  
     
     
         38 . (canceled)  
     
     
         39 . A method according to  claim 22 , which comprises adding a chelating agent or catalase to the formulation.  
     
     
         40 . (canceled)  
     
     
         41 . A method of delivering biological material by electrohydrodyamic processing of a liquid formulation containing biological material, which comprises conjugating the biological material with PEG prior to electrohydrodyamic processing.  
     
     
         42 . (canceled)  
     
     
         43 . (canceled)  
     
     
         44 . (canceled)  
     
     
         45 . (canceled)  
     
     
         46 . (canceled)  
     
     
         47 . A method of processing a liquid comprising at least one polymer and at least one volatile component, which comprises supplying the liquid to an outlet, subjecting liquid issuing from the outlet to an electric field to cause formation of at least one of a polymer fibre and fibrils and controlling the partial vapour pressure of the or at least one of the volatile constituents of the liquid in the environment into which the liquid issues or at least vicinity of the outlet to control the formation of the fibre or fibrils.  
     
     
         48 . A method according to  claim 47 , which comprises supplying the at least one volatile component to the environment into which the liquid issues or at least to the vicinity of the outlet to control the partial vapour pressure of the at least one volatile component.  
     
     
         49 . A method according to  claim 48 , which comprises providing around the outlet a shroud or collar for supplying the volatile component.  
     
     
         50 . A method according to  claim 49 , which comprises supplying additional volatile component to the shroud or collar.  
     
     
         51 . (canceled)  
     
     
         52 . (canceled)  
     
     
         53 . (canceled)  
     
     
         54 . (canceled)  
     
     
         55 . (canceled)  
     
     
         56 . (canceled)  
     
     
         57 . A method according to  claim 1 , which comprises conjugating the biological material with polyethylene glycol (PEG).  
     
     
         58 . (canceled)  
     
     
         59 . (canceled)  
     
     
         60 . (canceled)