<scp>l</scp>-Glutamic acid crystals of pure α form and uniform size distribution from continuous non-seeded reaction crystallization in slug flow

Zambrano, Consuelo Del Pilar Vega; Jiang, Mo

doi:10.1039/d2ce01528e

Cited by 3 publications

(3 citation statements)

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“…In this way, the mixing hydrodynamics and chemical conditions in each slug are still similar across different scales of total volumes, such as mixing time and induction time. Uniform-sized slugs were continuously generated by combining gas streams and solution streams in a milli-fluidic tubing , (Figure ). The uniform slug size is considered beneficial for the size uniformity of crystals produced from slugs at various scales, under chemical conditions for pure α-MnC 2 O 4 ·2H 2 O, as validated here with 2.6, 26, and 260 mL at an initial supersaturation of 7.5.…”

Section: Resultsmentioning

confidence: 99%

“…Then, we explored a direct precipitation pathway to α-MnC 2 O 4 ·2H 2 O (prism shape) and fast synthesis under similar reaction conditions (green arrow in Figure ) by replacing the “by-default” stirred-tank reactor with a slug flow at medium flow rates. Slug flow, similar to a series of self-mixed mini-batches from intrinsic recirculation, ,, had been applied to effectively create spatial uniformity for reaction and crystallization processes. − Here, we also evaluated the effect of slug flow on the selection of the solid form and precipitation pathway, such as from the perspective of extending the induction time. Then, a stable and scalable slug flow was generated to ensure solution spatial uniformity and good mixing, allowing synchronization of all molecules along the same direct precipitation pathway.…”

Section: Introductionmentioning

confidence: 99%

“…A wide variety of products contain active materials in crystalline forms, such as pharmaceuticals, fine chemicals, agricultural fertilizers, and energy storage devices. − The product quality and manufacturing process efficiency can be largely affected by the quality of these crystals, such as their solid/form purity, shape, and size distribution. − Generating solids of high purity can be challenging from fast precipitation (reactive crystallization) , as multiple possible solid forms and associated pathways at similar energy levels can exist. So far, it is still not fully understood how to achieve 100% purity for each solid form (switching among different crystallization pathways) of many molecules, except for some well-studied ones such as l -glutamic acid. − It is even more challenging to scalably precipitate into uniform microcrystals of a selected solid form, which requires synchronizing all molecules or crystals along the same precipitation pathway.…”

Section: Introductionmentioning

confidence: 99%

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Direct Precipitation Pathway to Pure α-MnC₂O₄·2H₂O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Kim,

Jiang

2024

Crystal Growth & Design

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Synthesizing uniform microcrystals of high solid purity is desired for process efficiency and product consistency, but it is often challenging to achieve due to its high uniformity (e.g., the coefficient of variation in both crystal size and aspect ratio is less than 0.5) and mild reaction conditions (e.g., pH ∼ 7, room temperature). An example crystal is α-MnC 2 O 4 •2H 2 O, whose current precipitation synthesis often takes place in stirred-tank reactors and requires acidic pH, elevated temperatures, and/or extended hours. Crystal size uniformity control is also lacking. This study first demonstrates the feasibility of mild reaction conditions for synthesizing α-MnC 2 O 4 •2H 2 O in a stirred tank, at a stoichiometric ratio of 1:1 and an initial supersaturation of 7.5. This synthesis follows an indirect pathway, with a solid MnC 2 O 4 •3H 2 O (less-stable form) quickly precipitated first and then slowly transformed in slurry to α-MnC 2 O 4 •2H 2 O (conglomerates). Further, a new direct solution-precipitation pathway to obtaining pure α-MnC 2 O 4 • 2H 2 O was discovered (without ever going through solid MnC 2 O 4 •3H 2 O and hour-long conversion) by replacing the "by-default" stirred tank/flask in the current synthesis with tubular slug flow at medium gas flow rates (e.g., 1.5−2.5 mL/min). With reduced gas flow rates in slug flow (from 10 to 1.5 mL/min), the induction time monotonically increases (from ∼50 to 137 s) and the mass portion of the undesired MnC 2 O 4 •3H 2 O among the reaction product solids also reduces (from ∼40 to 0%). Compared to a stirred tank at the same mild reaction conditions aimed at producing pure α-MnC 2 O 4 •2H 2 O, slug flow is able to reduce the reaction residence time from ∼30 to 0.3 h. The modular slug-flow design also allows not only incorporating production-cleaning cycles to prevent fouling but also scaling up the total volume using the same equipment. Throughout the continuous operation of 10 cycles (∼80 min) at medium gas flow rates, the product crystals from an initial supersaturation of 7.5 are consistently pure α-MnC 2 O 4 • 2H 2 O, uniform in size (average length ∼14 μm, coefficient of variation less than 0.2), and are all in prism shape (average aspect ratio ∼1.4, coefficient of variation less than 0.25).

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Direct Precipitation Pathway to Pure α-MnC₂O₄·2H₂O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Kim,

Jiang

2024

Crystal Growth & Design

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Automatic measurement of slug flow processes from in‐line videos

Qian,

Hulsizer,

Mou

et al. 2024

IET Image Processing

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Slug flow processes draw much attention in chemical and pharmaceutical manufacturing thanks to their ability to eliminate downtime costs and batch‐to‐batch variation. Using in‐line video can monitor the current process status and improve the stability of the slug flow. However, there are no effective image processing methods aiming at such videos from chemical experiments due to limited training sample size and the variety of experimental settings. The paper proposes a training‐free method to automatically detect and measure the slugs from in‐line videos. Multiple image features are fused to identify the slug shapes under various lighting conditions, a six‐point model is fitted to achieve better volume estimation, and a consistency score is estimated to quantify the detection uncertainty. The proposed algorithm achieves similar results to manual labeling for various types of slug flow processes, improving the accuracy of slug column estimation by a large margin compared to the existing automatic methods. Finally, using it to monitor the slug flow process's stability and the change of the slug volume in an injection point are demonstrated. The method not only shows that handcrafted image features have the capability for detection and segmentation from chemical experiment images but also paves the road for a training‐based algorithm for the task.

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Sequential Selection for Minimizing the Variance with Application to Crystallization Experiments

Kerfonta,

Kim,

Chen

et al. 2024

The American Statistician

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l-Glutamic acid crystals of pure α form and uniform size distribution from continuous non-seeded reaction crystallization in slug flow

Abstract: Desired goals of crystal synthesis include high crystal quality (e.g., pure solid forms and uniform size distribution) and high process efficiency and reproducibility.

Cited by 3 publications

References 52 publications

Direct Precipitation Pathway to Pure α-MnC₂O₄·2H₂O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Direct Precipitation Pathway to Pure α-MnC₂O₄·2H₂O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Automatic measurement of slug flow processes from in‐line videos

Sequential Selection for Minimizing the Variance with Application to Crystallization Experiments

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l-Glutamic acid crystals of pure α form and uniform size distribution from continuous non-seeded reaction crystallization in slug flow

Abstract: Desired goals of crystal synthesis include high crystal quality (e.g., pure solid forms and uniform size distribution) and high process efficiency and reproducibility.

Cited by 3 publications

References 52 publications

Direct Precipitation Pathway to Pure α-MnC2O4·2H2O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Direct Precipitation Pathway to Pure α-MnC2O4·2H2O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Automatic measurement of slug flow processes from in‐line videos

Sequential Selection for Minimizing the Variance with Application to Crystallization Experiments

Contact Info

Product

Resources

About

Direct Precipitation Pathway to Pure α-MnC₂O₄·2H₂O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals

Direct Precipitation Pathway to Pure α-MnC₂O₄·2H₂O Using Slug Flow toward the Scalable Nonfouling Fast Synthesis of Uniform Microcrystals