Sizing of a microfluidic device for confining a sample

Patent metadata

Field	Value
Publication number	US-11266986-B2
Application number	US-201615770088-A
Country	US
Kind code	B2
Filing date	Oct 21, 2016
Priority date	Oct 21, 2015
Publication date	Mar 8, 2022
Grant date	Mar 8, 2022

Abstract

The present invention relates to a method for manufacturing a microfluidic device. The microfluidic device includes an input zone adapted to receive a carrier fluid medium and a sample in suspension in the carrier fluid medium, the sample comprising at least one population of cells or microparticles, a confinement zone adapted to confine a selected amount of the sample, and an output zone adapted to discharge the carrier fluid medium and the sample in suspension in the carrier fluid medium.

First claim

The invention claimed is:

1. A method of manufacturing a microfluidic device, the microfluidic device including:
an input zone adapted to receive a carrier fluid medium and a sample in suspension in the carrier fluid medium, the sample comprising at least one population of cells or microparticles, the input zone corresponding to a cylindrical input tank of diameter D in ,
a confinement zone adapted to confine a selected amount of the sample, the confinement zone comprising a base of surface area S ch and length L ch and a side wall of height H ch , the confinement zone in fluid communication with the input zone via a first channel of length L in , height H in and width W in , and
an output zone adapted to discharge the carrier fluid medium and the sample in suspension in the carrier fluid medium, the output zone corresponding to a cylindrical output tank of diameter D out , the output zone communicating with the confinement zone via a second channel of length L out , height H out and width W out ,
the method comprises manufacturing the device as a function of the selected amount of the sample, the method comprising:
A. forming the confinement zone to have the length L ch and the height H ch , the length L ch and the height H ch being a function of the selected amount of the sample and of a selected coverage area fraction ϕ of the base of the confinement zone by the sample; and
B. forming the first channel to have the length L in , the height H in and the width W in and the second channel to have the length L out , the height H out and the width W out , by:
b1) calculating a sedimentation speed v sedi of a microparticle or a cell of the sample,
b2) determining a speed v ch of the carrier fluid medium in the confinement zone as a function of the sedimentation speed v sedi of the microparticle or the cell of the sample as per equation (1):

v
ch

≤

v
sedi

×

H
ch

L
ch

(
1
)

b3) determining a head loss ΔZ, which is necessary for a flow of the carrier fluid medium in the confinement zone allowing for deposition of the sample within the confinement zone in the microfluidic device, as a function of a volume of the carrier fluid medium injected between the input zone and the output zone, and
b4) determining geometric parameters of the microfluidic device from the head loss ΔZ and the speed v ch of the carrier fluid medium, the geometric parameters including the length L in , the height H in and the width W in of the first channel, the diameter D in of the cylindrical input tank, the length L out , the height H out and the width W out of the second channel, and the diameter D out of the cylindrical output tank.

2. The method according to claim 1 , wherein forming the confinement zone comprises:
A1) determining the surface area S ch of the base of the confinement zone as per Stokes formula (5):

ϕ
=

N
×
π
⁢

⁢

r
2

S
ch

(
5
)

with
ϕ being a fraction of a surface area of the base of the confinement zone to be covered by the sample,
r being a radius of a microparticle or a cell of the sample,
N being a number of microparticles or cells of the selected amount of the sample, defined by equation (6):
N=φ×V   (6)

with
φ being a concentration of cells or microparticles in the sample,
V being a volume of the sample entered in the microfluidic device at an instant t, defined as per equation (7):
V=Q×t   (7)

with
Q being a flow rate of the sample in the microfluidic device, and

A2) selecting the height H ch of the side wall of the microfluidic device, as a function of a selected volume in the confinement zone and associated manufacturing restrictions.

3. The method according to claim 1 , wherein the confinement zone has a cylindrical geometry, the base being circular and of diameter D ch such that the length L ch of the confinement zone is equal to the diameter D ch of the confinement zone.

4. The method according to claim 1 , wherein the sedimentation speed v sedi of a microparticle or a cell of the sample is calculated in sub-step b1) as per Stokes equation (8):

v
sedi

=

2
⁢

r
2

⁢
g
⁢

⁢
Δρ

9
⁢
η

(
8
)

with:
r being the radius of a microparticle or a cell of the sample,
g being the gravitational acceleration,
η being the dynamic viscosity of the carrier fluid medium, and
Δρ being the difference in density between that of the microparticles or cells of the sample and the carrier fluid medium.

5. The method according to claim 1 , wherein determining the geometric parameters of the microfluidic device comprises:
b41) choosing seven geometric parameters of the microfluidic device among the eight geometric parameters D in , H in , W in , L in , D out , H out , L out and W out ; and
b42) calculating a remaining geometric parameter among the eight geometric parameters as a function of the head loss ΔZ and of the speed v ch of the carrier fluid medium.

6. The method according to claim 5

Assignees

• Centre Nat Rech Scient
• Univ Grenoble Alpes

Inventors

• Honegger Thibault
• Maisonneuve Benoît

Classifications

• B01L3/502776

  specially adapted for focusing or laminating flows · CPC title

• C12M23/58

  Reaction vessels connected in series or in parallel (combinations of bioreactors with other apparatus, C12M43/00) · CPC title

• C12M23/16 Primary

  Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093) · CPC title

• C12M29/10

  Perfusion · CPC title

• C12M33/00

  Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus (chemical or physical laboratory apparatus in general B01L, devices for taking cell samples A61B10/0045, withdrawing or distributing predetermined quantities of fluid B01L99/00) · CPC title