# US 11,027,217 B2 · Electrically controlled nucleation and crystallization

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- Number: US 11,027,217 B2
- Document ID: US11027217B2
- Status: Granted
- Kind: B2
- Application number: 16/313,666
- Filed: 2017-06-27
- Published: 2020-10-01
- Granted: 2021-06-08
- Earliest claimed: 2016-06-27
- Assignees: Georgia State University Research Foundation, Inc.
- Applicants: Georgia State University Research Foundation, Inc.
- Inventors: Gangli Wang; Yan Li; Maksim M. Kvetny
- Web page: https://patentgrep.com/patent/US11027217B2

## CPC

- B01D 9/0063: {Control or regulation (control per se G05)}
- C30B 7/00: Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions (from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00)
- C30B 7/12: by electrolysis
- C30B 29/58: Macromolecular compounds
- C30B 30/02: using electric fields, e.g. electrolysis
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C30B: SINGLE-CRYSTAL GROWTH (by using ultra-high pressure, e.g. for the formation of diamonds, B01J3/06); UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL (zone-refining of metals or alloys C22B); PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE (casting of metals, casting of other substances by the same processes or devices B22D; working of plastics B29; modifying the physical structure of metals or alloys C21D, C22F); SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE (for producing semiconductor devices or parts thereof H10); APPARATUS THEREFOR

## Abstract

Disclosed herein are systems and methods for the controlled crystallization of a compound. The controlled crystallization is achieved by applying an electric field across solutions of target compound and precipitant, whereby the electric field controls the rate of mixing.

## Claims

### Claim 1

A crystallization system, comprising:
at least one receiving member comprising a first electrically conductive member;
at least one dispensing member comprising a second electrically conductive member, wherein the second electrical member is affixed to the receiving member;
wherein the first and second electrical members are coupled in electrical communication;
wherein the dispensing member comprises:
an electrically insulating material proximal to the receiving member, a portion of the electrically insulating material defining at least one aperture, said portion in fluid communication with a receiving chamber; and
whereby a complete electric circuit is obtained when electrolytes are present in the receiving and dispensing members.

### Claim 2 (depends on 1)

The system according to claim 1, wherein the portion defining at least one aperture has a dimension or surface area from 1 nm2 to 20 μm2.

### Claim 3 (depends on 1)

The system according to claim 1, comprising a single dispensing member.

### Claim 4 (depends on 1)

The system according to claim 1, comprising a plurality of dispensing members.

### Claim 5 (depends on 1)

The system according to claim 1, wherein the dispensing body comprises an elongated body terminating at one end with the portion of the electrically insulating material defining at least one aperture.

### Claim 6 (depends on 1)

The system according to claim 1, wherein the portion defines a plurality of micro-openings.

### Claim 7 (depends on 1)

The system according to claim 1, further comprising a pressure control system in communication with the dispensing chamber.

### Claim 8

A system for crystallization, comprising:
at least one receiving member comprising a first electrically conductive member;
at least one dispensing member comprising a second electrically conductive member;
wherein the first and second electrical members are coupled in electrical communication;
wherein the dispensing chamber and receiving chamber are separated by a porous membrane;
whereby a complete electric circuit is obtained when electrolytes are present in the receiving and dispensing members.

### Claim 9

A method for crystallizing a compound, the method comprising:
providing a solution of a compound in at least one receiving member comprising a first electrically conductive member;
providing a solution of a precipitate in at least one dispensing member comprising a second electrically conductive member;
wherein the receiving and dispensing electrical members are coupled in electrical communication; and
applying an electric field sufficient to controllably introduce the solution of precipitant into the solution of compound, wherein the applying an electric field comprises
applying a first electric field sufficient to induce a nucleation of the compound at the one or more openings of the second receptacle, and applying a second electric field following nucleation, wherein the second electric field controls growth of the crystal.

### Claim 10 (depends on 9)

The method of claim 9, wherein the second electric field is different from the first electric field.

### Claim 11 (depends on 9)

The method of claim 9, wherein the first electric field is voltage-clamped (constant DC potential) or voltage-ramped; or the first electric field is current-clamped (constant current) or current-ramped; or the first electric field is a multi-segment combined DC-AC potential including a constant, pulsed and/or ramped waveform.

### Claim 12 (depends on 9)

The method of claim 9, wherein the second electric field is current-clamped or current ramped; or the second electric field is voltage-clamped or voltage ramped; or the second electric field is a multi-segment combined DC-AC potential including a constant and ramped waveform.

### Claim 13 (depends on 9)

The method of claim 9, wherein the first electric field is applied with oscillations at controlled/programmed amplitude and frequency.

### Claim 14 (depends on 9)

The method of claim 9, wherein the second electric field is applied with oscillations at controlled/programmed amplitude and frequency.

### Claim 15 (depends on 11)

The method according to claim 11, wherein the first electric field is a pulsed waveform comprising a triangular waveform, an AC sine, or a square wave.

### Claim 16 (depends on 9)

The method of claim 9, wherein the compound comprises a small molecule drug.

### Claim 17 (depends on 9)

The method of claim 9, wherein the compound comprises a peptide.

### Claim 18 (depends on 9)

The method of claim 9, wherein the compound comprises a protein.

### Claim 19 (depends on 9)

The method of claim 9, wherein the compound comprises a nucleic acid.

### Claim 20 (depends on 9)

The method of claim 9, wherein the compound comprises a complex.

### Claim 21 (depends on 9)

The method of claim 9, wherein the compound solution is a saturated solution, near saturated solution or super-saturated solution.

### Claim 22 (depends on 9)

The method of claim 9, wherein the precipitant comprises an anti-solvent.

### Claim 23 (depends on 9)

The method of claim 9, wherein the precipitant comprises an acid.

### Claim 24 (depends on 9)

The method of claim 9, wherein the precipitant comprises a base.

### Claim 25 (depends on 9)

The method of claim 9, wherein the precipitant comprises a precipitating reagent.
