Method for transferring material in a microfluidic or millifluidic device

Patent metadata

Field	Value
Publication number	US-2021283612-A1
Application number	US-201917252167-A
Country	US
Kind code	A1
Filing date	Jun 14, 2019
Priority date	Jun 14, 2018
Publication date	Sep 16, 2021
Grant date	—

Abstract

The present invention relates to a method for transferring material in a microfluidic or millifluidic device between a droplet of a first droplet train and a droplet of a second droplet train, as well as to the use of this method for the preparation of biological or chemical samples, the implementation of biological or chemical reactions, the screening of a molecule of synthetic or biological origin, or the screening or cultivation of microorganisms. The present invention also relates to a microfluidic or millifluidic device suitable for carrying out the method according to the invention.

First claim

1 . A method for transferring material between two droplets in a microfluidic or millifluidic device comprising:
a first microfluidic or millifluidic channel and a second microfluidic or millifluidic channel, a transfer channel connecting the first channel to the second channel, and a closing and opening system to control the opening and closing of the transfer channel and which comprises an open and a closed position,
said method comprising the following steps:
(a) putting the closing and opening system of the transfer channel in a closed position if it is in an open position;
(b) generating, in the first microfluidic or millifluidic channel, a first droplet train comprising a continuous phase, at least two droplets and optionally at least one spacer between two successive droplets A n and A n+1 where n≥1;
(c) generating, in the second microfluidic or millifluidic channel, a second droplet train comprising a continuous phase, at least two droplets and optionally at least one spacer between two successive droplets B m and B m+1 where m≥1;
(d) positioning a droplet A n of the first droplet train in front of the junction between the transfer channel and the first channel;
(e) positioning a droplet B m of the second droplet train in front of the junction between the transfer channel and the second channel;
(f) putting the closing and opening system of the transfer channel in an open position so as to allow:
the transfer of at least a part of the droplet A n of the first droplet train to the droplet B m of the second droplet train, or
the transfer of at least a part of the droplet B m of the second droplet train to the droplet A n of the first droplet train,
before putting the closing and opening system of the transfer channel back in the closed position;

(g) optionally repeating steps (d) to (f) one or more times with the same droplet A n or a different droplet of the first droplet train and with the same droplet B m or a different droplet of the second droplet train.

2 . The method according to claim 1 , wherein step (f) is carried out after steps (d) and (e) so that the closing and opening system of the transfer channel is placed in an open position once the droplets A n and B m are positioned respectively at each end of the transfer channel and allows the passage of material directly between the droplets A n and B m via the transfer channel.

3 . The method according to claim 2 , wherein, during step (f), the pressure in the first channel and/or the second channel is adjusted so that:
the pressure in the first channel is higher than the pressure in the second channel to allow the transfer of at least a part of the droplet A n of the first droplet train to the droplet B m of the second droplet train; or the pressure in the second channel is higher than the pressure in the first channel to allow the transfer of at least a part of the droplet B m of the second droplet train to the droplet A n of the first droplet train.

4 . The method according to claim 1 , wherein:
(i) the transfer channel comprises a second closing and opening system, the first closing and opening system being closer to the connection of the transfer channel to the first microfluidic or millifluidic channel than the second closing and opening system, and therefore the second closing and opening system is closer to the connection of the transfer channel to the second microfluidic or millifluidic channel than the first closing and opening system, both closing and opening systems being put in the closed position in step (a), or (ii) the closing and opening system of the transfer channel comprises a second open position so that:
its closed position prevents any passage of material in the transfer channel on either side of the closing and opening system,
its first open position allows the transfer of material from the first microfluidic or millifluidic channel to the transfer channel or, conversely, from the transfer channel to the first microfluidic or millifluidic channel,
its second open position allows the transfer of material from the second microfluidic or millifluidic channel to the transfer channel or, conversely, from the transfer channel to the second microfluidic or millifluidic channel, and
wherein step (f) comprises the following successive sub-steps: (f 1 ) putting the first closing and opening system of the transfer channel in an open position in case (i) or the closing and opening system of the transfer channel in its first open position in case (ii) so as to allow the transfer of at least a part of the droplet A n of the first droplet train to the transfer channel, then putting said closing and opening system of the transfer channel back in a closed position, (f 2 ) putting the second closing and opening system of the transfer channel in an open position in case (i) or the closing and opening system of the transfer channel in its second open position in case (ii) so as to allow the transfer of the material from the droplet A n of the first droplet train present in the transfer channel to the droplet B m of the second droplet train, then putting said closing and opening system of the transfer channel back in a closed position; or (f′ 1 ) putting the second closing and opening system of the transfer channel in an open position in case (i) or the closing and opening system of the transfer channel in its second open position in case (ii) so as to allow the transfer of at least a part of the droplet B m of the second droplet train to the transfer channel, then putting said closing and opening system of the transfer channel back in a closed position; (f 2 ) putting the first closing and opening system of the transfer channel in an open position in case (i) or the closing and opening system of the transfer channel in its first open position in case (ii) so as to allow the transfer of the material from the droplet B m of the second droplet train which is present in the transfer channel to the droplet A n of the first droplet train, then putting said closing and opening system of the transfer channel back in a closed position, wherein steps (f 1 ) and (f′ 2 ) are implemented after step (d) and steps (f 2 ) and (f′ 1 ) are implemented after step (e).

5 . The method according to claim 4 , wherein the transfer channel is further connected to a suction channel and to an addition channel, and
wherein the pressure is adjusted in the different channels as follows:
during step (f 1 ) or (f′ 1 ), the pressure in the donor channel is higher than the pressure in the suction channel, the donor channel being the first microfluidic or millifluidic channel in the context of step (f 1 ) and the second microfluidic or millifluidic channel in the context of step (f′ 1 ); then
during step (f 2 ) or (f′ 2 ), the pressure in the addition channel is higher than the pressure in the recipient channel, the recipient channel being the second microfluidic or millifluidic channel in the context of step (f 2 ) and the first microfluidic or millifluidic channel in the context of step (f′ 2 ).

6 . The method according to claim 1 , wherein the microfluidic or millifluidic device further comprises a droplet detection system.

7 . The method according to claim 1 , wherein the closing and opening system of the transfer channel is a cylinder valve, a translational valve, a pinch valves, or a solenoid valve.

8 . The method according to claim 1 , wherein the continuous phase is a mineral or fluorinated oil; the phase constituting the droplets comprises an aqueous solution; the phase constituting the optional spacer(s) is a gas or a liquid immiscible with the continuous phase and the phase constituting the droplets to be

Assignees

• Paris Sciences Lettres Quartier Latin
• Centre Nat Rech Scient
• Ecole Superieure Physique & Chimie Ind Ville De Paris

Inventors

• Dupin Jean-Baptiste
• Chaurasia Ankur Shubhlal
• Bibette Jérôme
• Bremond Nicolas
• Baudry Jean
• Sire Wilfried

Classifications

• B01L2400/06

  Valves, specific forms thereof · CPC title

• B01L2200/0673

  Handling of plugs of fluid surrounded by immiscible fluid · CPC title

• G01N35/08

  using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis · CPC title

• B01L2400/0487

  fluid pressure, pneumatics · CPC title

• B01L2300/0867

  Multiple inlets and one sample wells, e.g. mixing, dilution · CPC title