Continuous flow microfluidic systems and methods for producing self-assembled material particles

Abstract

A continuous flow microfluidic system for continuous flow operation of a microfluidic chip, characterized in that the flatness of the surface of the microfluidic chip and the flatness of the surface of the cover and base of the chip holder that holds the microfluidic chip are both 50 μm or less, and the pulsation rate of the continuous flow formed by the system is 5% or less. [Effects] Even when a fluid sample is introduced into a microfluidic chip at high pressure, self-assembled material particles such as lipid nanoparticles with high size uniformity can be produced well and stably, enabling the mass production of such self-assembled material particles.

Claims

1. A system for continuous flow operation of a microfluidic chip, comprising the following (1) to (4): (1) A first continuous flow pump that continuously supplies a first fluid from a first reservoir. (2) A second continuous flow pump that continuously supplies the second fluid from the second reservoir. (3) A microfluidic device comprising a microfluidic chip made of synthetic quartz glass having the following channels (a) to (c). (a) A first supply channel through which the first fluid flows. (b) A second supply channel through which the second fluid flows. (c) A mixing and diluting channel provided downstream of the confluence point where the first supply channel and the second supply channel merge over a certain length, through which a mixed fluid obtained by mixing the first fluid and the second fluid flows. (4) A discharge channel through which the mixed fluid discharged from the microfluidic device flows. The microfluidic device described in (3) above comprises the chip holder described in (a) below and the connector described in (b) below. (a) A chip holder comprising a cover and a base that are in contact with the surface of the microfluidic chip, and a fastener that connects and fixes the cover and the base, wherein the microfluidic chip is placed between the cover and the base, and the cover and the base are connected and fixed with the fastener, thereby fixing the microfluidic chip in close contact with the cover and the base. (b) A connector that penetrates at least one of the cover and the base, with one end connected to an opening provided at the upstream end of the first supply channel of the microfluidic chip, the upstream end of the second supply channel, and the downstream end of the mixing and diluting channel, respectively, and the other end forming a supply port for the first fluid or the second fluid or an outlet for the mixed fluid. A continuous flow microfluidic system characterized in that the cover and base have a plate-like shape, their inner surfaces are the same shape as the surface of the microfluidic chip and larger than the surface of the microfluidic chip, the flatness of the surface of the microfluidic chip in contact with the cover and the flatness of the surface of the microfluidic chip in contact with the base are both 50 μm or less, the flatness of the surface of the cover in contact with the microfluidic chip and the flatness of the surface of the base in contact with the microfluidic chip are both 50 μm or less, and the pulsation rate of the continuous flow formed by the system is 5% or less.

2. The continuous flow microfluidic system according to claim 1, comprising a dilution section including a third continuous flow pump that continuously supplies a dilution solution from a third reservoir, and a dilution channel that supplies the dilution solution discharged from the third continuous flow pump downstream of the microfluidic device in the system to mix the dilution solution with the mixed fluid.

3. The continuous flow microfluidic system according to claim 1 or 2, further comprising a waste recovery channel branched from the discharge channel via a waste valve.

4. The continuous flow microfluidic system according to claim 1 or 2, having a processing capacity of at least 3 L / h per mixing and dilution channel.

5. The continuous flow microfluidic system according to claim 1 or 2, wherein at least a portion of the mixing and diluting channel has a bent channel section formed by a plurality of structural elements installed in the channel, and when the axial direction of the mixing and diluting channel is the X direction, the width direction of the mixing and diluting channel perpendicular to the X direction is the Y direction, and the width of the mixing and diluting channel upstream of the bent channel section in the Y direction is [y0], the structural elements, which are arranged to protrude inward from the side walls facing each other along the Y direction in the mixing and diluting channel, are installed alternately at predetermined intervals along the X direction, and the protrusion width of the structural elements in the Y direction is 1 / 2 [y0] or more and less than 1 [y0].

6. A continuous flow microfluidic system for producing self-assembled material particles, wherein in the mixing and diluting channel, a self-assembled material-containing solution supplied from one of the first supply channel and the second supply channel is diluted with a diluent supplied from the other channel to form self-assembled material particles.

7. A method for producing self-assembled material particles, comprising the step of diluting a self-assembled material-containing solution with a diluent to obtain a liquid containing self-assembled material particles, wherein the step is carried out using the continuous flow microfluidic system described in claim 6.

8. The manufacturing method according to claim 7, wherein the self-assembling material is a lipid or an amphiphilic substance.

9. The manufacturing method according to claim 7 or 8, wherein the dilution medium is selected from aqueous solutions, buffer solutions, nucleic acid-containing aqueous solutions, protein-containing aqueous solutions, peptide-containing aqueous solutions, adjuvant-containing aqueous solutions, and mixtures thereof.

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