TECHNICAL FIELD

The present disclosure generally relates to the field of crystallization, and more specifically, to systems and methods for laser-induced nucleation.

BACKGROUND

Crystallization has been used in science and commerce as an efficient method of concentrating and purifying chemicals. Nonphotochemical laser-induced nucleation (NPLIN) is a type of nucleation method in which nucleation is achieved by the action of light on matter. NPLIN has been observed in various aqueous solutions, including urea, glycine, simple salts such as alkali halides, and proteins. The NPLIN of carbon dioxide bubbles from carbonated water has also been observed.

Three mechanisms have been proposed to account for NPLIN. In the optical Kerr effect mechanism, the applied optical electric field induces the alignment of solute molecules in disordered solute clusters, lowering the barrier to nucleation. In the dielectric polarization (DP) model, the applied electric field lowers the energy of slightly sub-critical solute clusters, such that they become critical and nucleate. In the colloidal impurity heating mechanism, nanoscale solvent vapor bubbles are formed from the heat generated when impurity particles absorb incident laser light. These bubbles act as sites for heterogeneous nucleation. However, the underlying mechanism remains an open question as any one of the proposed mechanisms explains only part of the reported experimental observations. A need exists for improved technology capable of characterizing crystallization of matter using nonphotochemical laser-induced nucleation.

SUMMARY

The systems and methods described in this application relate to laser-induced nucleation in continuous flow. In conjunction with an optical field, millifluidic laser-induced nucleation can provide for a controlled nucleation process of useful products such as pharmaceuticals, drug polymorphs, and crystalline compounds. The properties of these products can be controlled and tailored through the controlled nucleation process.

The systems and methods described in this application relate to laser-induced nucleation in continuous flow. One aspect of the present disclosure is directed to a method of laser-induced nucleation in continuous flow and can include injecting at least one of a saturated solution, an undersaturated solution, or a supersaturated solution through an inlet of a device. The method can include converting the saturated solution or undersaturated solution into supersaturated solution by changing a temperature of the saturated or undersaturated solution. The method can include passing one or more laser pulses through the supersaturated solution within the device. The method can include flowing at least one of the saturated solution or the supersaturated solution or the undersaturated solution through an outlet of the device.

In some embodiments, the method includes nucleating crystals, responsive to passing the one or more laser pulses through the supersaturated solution within the device, from the supersaturated solution. The method includes collecting the crystals from the device. In some embodiments, the method includes contacting the device with a thermoelectric cooler. In some embodiments, the method includes characterizing, in situ, at least one of crystal size, shape, growth rate, number of crystals, polydispersity, or polymorphism. In some embodiments, the method includes passing the least one of the saturated solution, undersaturated solution, or supersaturated solution through a filter. In some embodiments, the method includes operating the device at a temperature above 0 K. In some embodiments, the method includes operating the device at a pressure below, above, or at 1 bar. In some embodiments, the method includes nucleating crystals from the supersaturated solution resulting from a chemical reaction such as the Heck Reaction, Suzuki Reaction, or Buchwald-Hartwig amination, or any chemical reaction carried out under conditions that result in the formation of supersaturated solution containing crystalline products or byproducts. The method includes selectively inducing nucleation in the bulk flow instead of on equipment or catalyst surfaces, thus improving solids handling.

One aspect of the present disclosure is directed to a method of laser-induced nucleation in continuous flow. The method includes providing a device. The method includes injecting a fluid through an inlet of the device. The method includes passing one or more laser pulses through the flowing fluid within the device. The method includes flowing the fluid through an outlet of the device.

In some embodiments, the flowing fluid is a single phase flow. In some embodiments, the flowing fluid is a multiphase flow. In some embodiments, the method includes nucleating crystals, responsive to passing the one or more laser pulses through the flowing fluid within the device, from a supersaturated solution. The method includes collecting the crystals from the device. In some embodiments, the method includes contacting the device with a thermoelectric cooler. In some embodiments, the method includes characterizing, in situ, at least one of crystal size, shape, growth rate, number of crystals, polydispersity, or polymorphism. In some embodiments, the method includes passing the least one of a saturated solution, undersaturated solution, or supersaturated solution through a filter. In some embodiments, the method includes operating the device at a temperature above 0 K. In some embodiments, the method includes operating the device at a pressure below, above, or at 1 bar. In some embodiments, the method includes nucleating crystals from a supersaturated solution resulting from a chemical reaction such as the Heck Reaction, Suzuki Reaction, or Buchwald-Hartwig amination, or any chemical reaction carried out under conditions that result in the formation of crystalline products or byproducts. In some embodiments, the method includes inducing nucleation in bulk flow instead of on equipment or catalyst surfaces.

