The Possibilities Behind Continuous Chemical Reactor Technology

Continuous chemical reactors enable ultra-turbulent mixing of reactant streams continuously. Reactant mixtures are highly pressurized and subjected to high shear in microchannels. This report explores their potential

By Irwin Gruverman

Just the Facts About CCR Technology • The product classes that CCR technology can address include fine chemical manufacture including APIs, catalysts, fine coatings, injectable drugs, superconductors, fine grinding media, pigments, and ceramics. • Advantages of the technology include lower capital cost, continuous operation at high efficiency, control of stoichiometry, reliable scale-up, and control of product purity, size, uniformity, and phase purity.

Commercial chemical reaction practice utilizes batch reactors, typically agitated and temperature controlled. Mixing is inefficient — reactant-containing liquid structures, often a millimeter or greater in size, do not interact efficiently and so prevent rapid reaction. Diffusion rates of reactant molecules from the large liquid structures control overall reactor kinetic performance. This dynamic leads to long reaction times, allows slow reactions to produce impurities, and affords little or no control of product properties — particularly size and crystal structure. Even if otherwise acceptable, slow overall reaction rates limit efficiency of operation. A major drawback of legacy reactor equipment is its batch nature, requiring multiple reactors for scale-up and consequent loss of uniformity and reproducibility in reaction product characteristics. While continuous reaction schemes are possible with linked batch reactors, product control is limited by the slow reaction rates realized. Capital costs for high production throughputs are high for multiple batch or linked reactor systems. It should be noted that nanomaterial preparation by precipitation is often impossible in batch reactors.

New microreactors address the need for examining novel fast chemistry by miniaturizing flow channels and reaction spaces, thus reducing diffusion dimensions. These units cannot be scaled up since flow path dimensions cannot be enlarged much. Thus, scale-up requires use of many parallel microreactors, an expensive equipment cost issue that demands that uniformity and reproducibility be questioned. In addition, precipitation reactions or the presence of solids in the reacting streams cause clogging. These microreactors are operated at low pressure with resultant typical residence times of a few seconds to minutes.

Operation at elevated pressures in the 5,000 to 25,000 psi range would shorten residence time, minimize clogging problems, and enable scale-up to the kilograms/minute range in a single continuous reactor. Further, the kinetic energy in liquid streams at these pressures can be utilized to form nanostructures by stopping the high velocity streams in restricted reaction spaces, resulting in ultra-turbulent mixing at the point of reaction.

Combinatorial parallel reaction development can be performed in microreactors, albeit with the disadvantage of low pressure, which limits the ability to control reaction kinetics and limits classes of reactions that can be utilized. Precipitations and suspension reactants are not permitted. Such experiments can define the parameter space in which a useful production reactor scheme can be sought.

Now continuous chemical reactors (CCR) are available. These enable ultra-turbulent mixing of reactant streams continuously. Reactant mixtures are highly pressurized, are subjected to high shear in microchannels, and enter a microliter size reaction chamber at a velocity of several hundred feet/second. Shear rates exceed 10⁶ sec^-1, several orders of magnitude greater than high-speed stirring in a batch reactor or 10 times that achieved in high-pressure homogenizers. Reactant-bearing liquid structures are reduced to nanometer scale, often approaching molecular size. Diffusion resistance becomes minimal, and reaction kinetics are rapid and exclude slow side reactions. Digital control of inlet streams ensures design stoichiometry and shear levels during processing.

A CCR consists of a high-pressure mixing system capable of subjecting a reaction mixture to high pressure and shear in a very restricted reaction zone. Control of flow and stoichiometry, coupled with ultra-turbulent mixing to minimize diffusion resistance to reaction, allows continuous reaction with precise control of product characteristics.

A standard materials processor schematic is shown in Figure 1. The reaction mixture is formed as a premix and then flows into an intensifier pump. The mixture is pressurized (up to 40,000 psi) and then conducted through microchannels (in which streamline flow minimizes mixing) to a microliter-size reaction zone in which the kinetic energy of the pressurized liquids is dissipated, causing ultra-turbulent mixing. The delay time between the pump and reaction zone is 0.1 to 1 second. For slower reactions, this delay and a controlled premix storage time may be practical. Serial treatment in such processors and the use of an online accumulator can maintain continuous operation.

For fast reactions — 95 percent completion in 1 to 5 seconds — premix storage is not acceptable. By using metered coaxial feed of reactants into the processor, the delay time prior to reaching the reaction zone will usually be short enough to allow continuous one-pass operation with high yield and full control of reaction product size, size distribution, purity, and phase identity. Even if some reaction products form en route to the ultra-turbulent reaction zone, this can be minimized by the appropriate choice of upstream channel size in order to maintain the streamline flow of large liquid structures prior to reaction. Further, for precipitated reaction products, significant remodeling of freshly formed solids can occur in the ultra-turbulent reaction chamber. A schematic drawing of such a system is shown in Figure 2.

For very fast reactions — 95 percent completion in less than 1 second — where exposure of reactants prior to reacting the ultra-turbulent zone would lead to non-uniform reaction conditions and unacceptable variations of product characteristics, a direct interaction mixer/reactor is able to introduce two or more independent pressurized streams, which are forced to collide at high velocity in a microliter-size reaction chamber with shear levels exceeding 10⁶ sec^-1. Reacting molecules interact at the nanometer scale, and precipitation reactions produce nanoparticles uniformly and continuously. A schematic drawing of such a mixer/reactor is shown in Figure 3.

CCR technology can be adapted to multiplex a single high-pressure stream to interact with multiple lower pressure streams of varying composition on a continuous basis. Throughputs in the gram-per-minute range are achievable. Scale-up to 20 kg per minute can be based on the multiplex experimental results. The ability to attain linear scale-up, over a 100,000-fold throughput range, has been characteristic of the technology.

Irwin Gruverman is the CEO and chairman of Microfluidics Corp. and MFIC Corp. Microfluidics, a division of MFIC Corp., pioneered the Microfluidizer high-pressure fluids processor technology, which is used in R&D laboratories as well as pilot and production manufacturing operations. Microfluidizer high-shear processors are widely used in the pharmaceutical, biotechnology, digital ink, microelectronics, food, chemical, and personal care industries. More information is available by contacting the company in Newton, MA, at 617-969-5452 or by visiting www.microfluidicscorp.com.