# US 12,766,865 B2 · Patterning-mediated supramolecular assembly of lipids into nanostructures

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- Number: US 12,766,865 B2
- Document ID: US12766865B2
- Status: Granted
- Kind: B2
- Application number: 18/066,387
- Filed: 2022-12-15
- Published: 2023-06-15
- Granted: 2026-10-20
- Earliest claimed: 2021-12-15
- Assignees: Smart Products for Consulting and Research
- Applicants: Smart Products for Consulting and Research
- Inventors: Ali Hussain Alhasan; Samar Abdullah Alsudir
- Web page: https://patentgrep.com/patent/US12766865B2

## CPC

- B41M 1/26: Printing on other surfaces than ordinary paper (B41M1/40 takes precedence)
- G03F 7/0002: {Lithographic processes using patterning methods other than those involving the exposure to radiation, e.g. by stamping}
- B41M: PRINTING, DUPLICATING, MARKING, OR COPYING PROCESSES; COLOUR PRINTING, (correction of typographical errors B41J; processes for applying transfer pictures or the like B44C1/16; fluid media for correction of typographical errors by coating C09D10/00; printing textiles D06P)
- G03F: PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR; (phototypographic composing devices B41B; photosensitive materials or processes for photographic purposes G03C; electrophotography, sensitive layers or processes therefor G03G)

## Abstract

Methods of making a supramolecular structure of lipids. The methods include providing an ink made of an aqueous solution of lipid micelles that are deposited onto a polymer pen or an array of polymer pens, such as by an electrospray technique to achieve a homogenous coverage of single and isolated micelles. The method further comprises transferring the ink to a substrate using polymer pen lithography (PPL). Nanoconfinement of the lipid micelles associated with the disclosed method, allow the lipid micelles to rearrange and ultimately lead to a highly ordered and homogenous supramolecular lipid structure. A supramolecular assembly made using the disclosed method and nanoscale delivery system comprising the supramolecular assembly of lipids are further disclosed.

## Claims

### Claim 1

A method of forming a supramolecular structure of lipids, said method comprising:
providing an ink comprising an aqueous solution of lipids that form a primary structure, wherein the concentration of the lipid in the aqueous solution is above critical micelle concentration (CMC) in order to form a micellar ink of lipids in said aqueous solution;
depositing the micellar ink of lipids in the aqueous solution onto one or more polymer pens;
printing the micellar ink of lipids onto a substrate with the one or more polymer pens using polymer pen lithography (PPL), wherein the printed lipid micelles rearrange during printing on the substrate to form a secondary structure of patterned lipids;
performing at least one post-printing treatment on the secondary structure of patterned lipids, wherein the at least one post-printing treatment step on the secondary structure of patterned lipids forms a tertiary structure of patterned lipids by self-assembly of said lipids, wherein the post-printing treatment comprises chemically treating the patterned lipids with a solvent and sonochemical treatment, mechanical agitation, or a combination thereof; and
performing at least one treatment step on the tertiary structure of the self-assembled lipids to form a quaternary structure of patterned lipids by self-assembly of said lipids, wherein the at least one treatment step comprises solvent evaporation.

### Claim 2 (depends on 1)

The method of claim 1, wherein said depositing is performed using electrospraying, and the one or more polymer pens are plasma cleaned using an oxygen gas prior to electrospraying.

### Claim 3 (depends on 2)

The method of claim 2, wherein electrospraying is performed using a voltage ranging from 7.0 to 9.0 kV, a flow rate ranging from 0.5 mL/hr to 1.5 mL/hr, for a duration of 5 to 15 min, wherein the injector-to-collector distance ranges from 5 to 15 cm.

### Claim 4 (depends on 1)

The method of claim 1, wherein the secondary structure of patterned lipids is selected from a disk, a sheet, or combinations thereof.

### Claim 5 (depends on 4)

The method of claim 4, wherein the polymer pen lithography is performed using an array of polymer pens and with printing force that is sufficient to change the shape of the secondary structure from a disk to a sheet.

### Claim 6 (depends on 5)

The method of claim 5, wherein the printing force ranges from 150 to 450 mN.

### Claim 7 (depends on 1)

The method of claim 1, wherein printing is performed at a temperature ranging from 30 to 34° C. and a relative humidity (RH) ranging from RH 90-94%.

### Claim 8 (depends on 1)

The method of claim 1, wherein the secondary structure comprises ribbons, sheets, disks, or combinations thereof, and when said secondary structure of patterned lipids comprises sheets or disks, they are larger in size than the primary structure.

### Claim 9 (depends on 1)

The method of claim 1, wherein the tertiary structure comprises curled ribbons, rolled sheets, or combinations thereof, and when said tertiary structure comprises curled ribbons or rolled sheets they are smaller in size than the secondary structure.

### Claim 10 (depends on 1)

The method of claim 1, wherein the rate of solvent evaporation is regulated to change the shape of the quaternary structure, the shape is selected from nanopalms, discotic liquid crystals, cochleate or combinations thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein the solvent comprises a mixture of CHCl3/EtOH/DDW.

### Claim 12 (depends on 1)

The method of claim 1, wherein the self-assembly of secondary lipid structures is intramolecular and mediated by nanoconfinement.

### Claim 13 (depends on 12)

The method of claim 12, wherein the one or more polymer pens have nanoscale tips that result in nanoconfinement of the secondary lipid structure.

### Claim 14 (depends on 1)

The method of claim 1, wherein prior to depositing, the aqueous solution of lipids micelles is held at a temperature and humidity for a time sufficient to impart the ink with desired viscosity properties.

### Claim 15 (depends on 1)

The method of claim 1, wherein the polymer pen comprises one or more elastomeric pens made of polydimethylsiloxane (PDMS).

### Claim 16 (depends on 1)

The method of claim 1, wherein the quaternary structure comprises an ordered and homogenous supramolecular lipid structure having stability for up to 120 days.

### Claim 17 (depends on 1)

The method of claim 1, wherein the polymer pen lithography is performed using an array of polymer pens comprising 500 to 50,000 pens in said array.

### Claim 18 (depends on 1)

A supramolecular assembly of lipids made by the method of claim 1.

### Claim 19 (depends on 18)

A supramolecular assembly of claim 18, which is in the form of nanopalms, discotic liquid crystals, cochleate, or combinations thereof.

### Claim 20 (depends on 18)

A nanoscale delivery system comprising the supramolecular assembly of lipids of claim 18.

### Claim 21 (depends on 20)

The nanoscale delivery system of claim 20, which is configured to deliver a medicinal component, a protein, a gene or portions thereof, a chemical, a nutrient, a cosmetic, a food product, a paint, a pesticide, or combinations thereof.

### Claim 22 (depends on 21)

The nanoscale delivery system of claim 21, wherein the medicinal component is delivered to a living organ.

### Claim 23 (depends on 21)

The nanoscale delivery system of claim 21, wherein the protein, gene or portions thereof comprise mRNA, DNA, or CRISPER-Cas9.
