Gas separation: processes – Solid sorption – And regeneration
Reexamination Certificate
2001-01-17
2003-09-30
Hopkins, Robert A. (Department: 1724)
Gas separation: processes
Solid sorption
And regeneration
C096S143000
Reexamination Certificate
active
06626982
ABSTRACT:
The invention relates to adsorbing chemical samples onto inert carriers to form highly stable free flowing solid for long term storage in, for example, a proprietary compound collection.
Large collections of chemical compounds are valuable assets of research organisations. Compound collections are used in the search for agents with novel pharmaceutical, agrochemical or other fine chemical applications and are a valuable source of structural and chemical diversity used in identifying new leads as potential inhibitors of a biological target. Compound collections may contain more than 100,000 different compounds and due to increasingly efficient compound acquisition, either through commercial sources, or by high throughput synthesis, compound collections with more than 1 million different compounds are now of a typical size in some research organisations.
The handling of samples within large compound collections for the purposes of storage, retrieval and testing presents numerous problems. In most organisations samples are obtained and stored as crystalline or amorphous powders and can be dispensed relatively easily by weighing, although this often needs to be done manually because of the varying nature of the solids. Some samples are made or obtained as glassy solids, syrups, oils or liquids and are subsequently stored in these forms. The weighing of these samples is often very time consuming and wasteful.
High throughput multiple parallel synthesis (HTMPS) can generate very large numbers of individual compounds, typically 100-5000 per week, but the sample size is usually small, <100 mg. To try and obtain all or most of these samples as crystalline or amorphous powders using the methods normally available to chemists would increase the overall synthesis time to such an extent that the HTMPS process would be impractical. To avoid this problem, compounds from HTMPS are stored sometimes as dry films or as solutions, usually in dimethyl sulphoxide (DMSO). The dispensing of compounds stored as dry films is often very difficult, and the difficulty increases significantly as the sample size decreases. Compounds stored as solutions can be dispensed quickly and accurately, but the manipulation and storage of the solutions subsequent to, and after, dispensing can be very problematical especially in compound handling systems designed to handle solids. In addition, some samples are unstable in solution and decompose on prolonged storage, even at low temperatures.
Increasingly the demands of a compound collection are changing. With the advent of high throughput screening (HTS) a whole compound collection of, for example, 100,000 compounds may be screened in a number of days against a new biological target, using automated or semi-automated procedures. Faced with the need for more rapid dispensing of compounds from the compound collection, the small sample size needed and the large numbers of different sample types existing in a compound collection, current systems of storage and dispensing are increasingly incompatible with modem needs. For example, a typical sample size of compound sample needed to be dispensed for HTS may be less than 0.1 mg, but despite weight variations of ±10% being tolerated for the purposes of screening, including HTS, it is not practicable to rapidly dispense such small sample sizes.
We have found that it is possible to store and retrieve compound samples, even after an extended duration of storage, by adsorbing the compound onto an inert carrier.
We have found that if the same inert carrier is used for a number of compounds, of different molecular weight, then only a single weight or volume of compound adsorbed onto an inert carrier is required to produce a substantially similar quantity (up to +/−15%, ideally +/−10%), in moles, of compound sample, after being extracted from the inert carrier, provided that the amount of inert carrier is in a large excess to the compound sample adsorbed onto it. Such a system lends itself to automation and hence rapid dispensing of compound samples because similar/identical weights, or volumes, of inert support with adsorbed compound can be measured in order that a similar amount, in moles, of compound sample is dispensed, after extraction, even when the concentration of compound adsorbed onto the inert support varies from sample to sample.
We present as a first feature of the invention a method of dispensing a compound sample, which comprises (1) measuring an amount of compound which is adsorbed onto an inert carrier, (2) extracting the compound from the inert carrier, and (3) dispensing the compound sample.
Preferably the inert carrier is in a large excess to the compound adsorbed onto it. The molar amount of the compound extracted from the inert carrier when in large excess to the compound adsorbed onto it, is directly related to the amount of compound plus inert carrier measured and not the molecular weight of the compound.
A further feature of the invention is an inert carrier having adsorbed onto it a compound characterised in that the compound is adsorbed onto a large excess of the inert carrier.
A further feature of the invention is a method of dispensing compound samples of substantially similar molar quantity which comprises (1) for each compound measuring an amount of compound which is adsorbed onto a large excess of an inert carrier, wherein the amount measured is substantially the same for each sample (2) extracting the compounds from the inert carrier, and (3) dipensing the compound samples.
The exact ratio of inert carrier to adsorbed compounds is unimportant provided that there is a “large excess” of inert carrier, for guidance it is intended that there is at least a 100, preferably at least a 200, 500, 1000 or 5,000, fold excess of inert carrier, in grams, compared with adsorbed compound, in moles. Preferred levels of adsorption are less that 400 &mgr;mol, preferably less than 300 &mgr;mol or less than 200 &mgr;mol, of adsorbed compound per gram of inert carrier.
The measurement used in dispensing the inert carrier plus adsorbed compound may be by weight, volume or any other means, preferably by volume. Typical weights that may be measured with levels of adsorption described above include from 10 to 250 mg, preferably 10 to 125 mg, of inert support and adsorbed compound. Typical volumes that may be measured include from 15 &mgr;l to 600 &mgr;l, preferably from 15 &mgr;l to 300 &mgr;l, depending upon the density of the inert carrier used.
We present as a further feature of the invention a method of dispensing a subgram (preferably less than 1 mg, or less than 0.1 mg, or even less than 0.05 mg) amount of compound sample, which comprises (1) adsorbing the compound onto an inert carrier, wherein the inert carrier is in a large excess to the compound, (2) measuring an amount of the adsorbed compound and inert carrier, (3) extracting the compound from the inert carrier and (4) dispensing the compound sample.
Ideally adsorption is achieved by contacting a solution of the compound dissolved in a suitable solvent, with the inert carrier and then removing the solvent, for example by evaporation. Ideally extraction is achieved by contacting the inert carrier with the required compound adsorbed on it with a suitable solvent for the adsorbed compound, which is not a solvent for the inert carrier, and separating the inert carrier from the solution.
The compound may be one of any number of different compounds, such as within a compound collection and as such represents a further feature of the invention.
Suitable inert carriers include those made from silicon, either as silicon oxides, such as sands, glass etc.; or in the form of silicates, such as mica, clay, feldspar, including, for example, the following commercially available silicas; Florosil™, Davisil™, Kiesegel™, C18 derivatised silica (C18), silanised silca gel 60 (Si-60) and other bonded silicas. Other inert carriers include aluminas, charcoals, resins, polymers and celluloses. Particular materials are microporous glass, controlled pore gl
AstraZeneca AB
Fish & Richardson PC
Hopkins Robert A.
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