Deterministic ratchet for sub-micrometer bioparticle separation

Patent metadata

Field	Value
Publication number	US-11944967-B2
Application number	US-202117524976-A
Country	US
Kind code	B2
Filing date	Nov 12, 2021
Priority date	Dec 19, 2017
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

Sub-micrometer bioparticles are separated by size in a microfluidic channel utilizing a ratchet migration mechanism. A structure within the microfluidic channel includes an array of micro-posts arranged in laterally shifted rows. Reservoirs are disposed at each end of the microfluidic channel. A biased AC potential is applied across the channel via electrodes immersed into fluid in each of the reservoirs to induce a non-uniform electric field through the microfluidic channel. The applied potential comprises a first waveform with a first frequency that induces electro-kinetic flow of sub-micrometer bioparticles in the microfluidic channel, and an intermittent superimposed second waveform with a higher frequency. The second waveform selectively induces a dielectrophoretic trapping force to selectively impart ratchet migration based on particle size for separating the sub-micrometer bioparticles by size in the microfluidic channel.

First claim

What is claimed is:

1. A method for separating sub-micrometer sized bioparticles, the method comprising:
depositing a fluidic sample in a microfluidic channel, wherein a plurality of micro-posts are disposed within the microfluidic channel; and
applying an electric field gradient to the fluidic sample to induce transport of sub-micrometer sized bioparticles in the fluidic sample by
applying a first electrical field waveform to the fluidic sample in the microfluidic channel,
applying a second electrical field waveform superimposed on the first electrical field waveform during a first portion of a period of the first electrical field waveform, wherein a frequency of the second electrical field waveform is higher than a frequency of the first electrical field waveform, and
removing the second electrical field waveform during a second portion of the period of the first electrical field waveform, wherein periodically applying and removing the superimposed second electrical field waveform separates the sub-micrometer sized bioparticles by size.

2. The method of claim 1 , wherein applying the first electric field waveform includes applying a square wave having an amplitude, a frequency, and a DC offset voltage.

3. The method of claim 2 , wherein applying the second electrical field waveform superimposed on the first electrical field waveform during the first portion of the period of the first electrical field waveform includes applying the second electrical field waveform superimposed on the square wave during a high period of the square wave, and wherein removing the second electrical field waveform during the second portion of the period of the first electrical waveform includes removing the second electrical field waveform during a low period of the square wave.

4. The method of claim 3 ,
wherein applying the first electrical field waveform causes bioparticles in the microfluidic channel to move in a first direction towards a first end of the microfluidic channel during the low period of the first electrical field waveform,
wherein applying the first electrical field waveform causes a first plurality of bioparticles in the microfluidic channel bioparticles to move in a second direction towards a second end of the microfluidic channel during the high period of the first electrical field waveform while applying the second electrical field waveform restricts movement of a second plurality of bioparticles in the second direction during the high period of the first electrical field waveform, and
wherein the bioparticles of the second plurality of bioparticles are larger than the bioparticles of the first plurality of bioparticles.

5. The method of claim 2 , wherein applying the second electrical field waveform superimposed on the first electrical field waveform during the first portion of the period of the first electrical field waveform includes applying the second electrical field waveform superimposed on the square wave during a low period of the square wave, and wherein removing the second electrical field waveform during the second portion of the period of the first electrical waveform includes removing the second electrical field waveform during a high period of the square wave.

6. The method of claim 5 ,
wherein applying the first electrical field waveform causes bioparticles in the microfluidic channel to move in a first direction towards a first end of the microfluidic channel during the high period of the first electrical field waveform,
wherein applying the first electrical field waveform causes a first plurality of bioparticles in the microfluidic channel bioparticles to move in a second direction towards a second end of the microfluidic channel during the low period of the first electrical field waveform while applying the second electrical field waveform restricts movement of a second plurality of bioparticles in the second direction during the low period of the first electrical field waveform, and
wherein the bioparticles of the second plurality of bioparticles are larger than the bioparticles of the first plurality of bioparticles.

7. The method of claim 1 , wherein applying the second electrical field waveform includes applying a sinusoidal wave.

8. The method of claim 1 , wherein applying the electrical field gradient causes the sub-micrometer sized bioparticles to separate by migration based on size by causing a first plurality of bioparticles to migrate towards a first end of the microfluidic channel and causing a second plurality of bioparticles to migrate towards a second end of the microfluidic channel.

9. The method of claim 8 , wherein the fluidic sample in the microfluidic channel exhibits no net flow into any single outlet channel during application of the electric field gradient.

10. The method of claim 1 , wherein the micro-posts are oval-shaped, circular shaped, half-circle shaped, tip-shaped, or needle shaped.

11. The method of claim 1 , wherein a first row of the plurality of micro-posts is offset a predetermined amount from an adjacent second row of the plurality of micro-posts.

12. The method of claim 1 , wherein the first electrical field waveform is characterized as

{

-

U

a
⁢

c
1

×

sgn

[

sin
⁡
(

2
⁢
π

τ

⁢
t

)

]

+

U

d
⁢
c

}

where U dc is a magnitude of a DC offset voltage of the first electrical field waveform and U ac_1 is the amplitude of the first electrical field waveform.

13. The method of claim 1 , wherein the second electrical field waveform is characterized as

{

U

ac
⁢
_

⁢
2

×

1
2

⁢

{

sgn

[

sin
⁢

(

Assignees

• Ros Alexandra
• Kim Daihyun
• Luo Jinghui
• Univ Arizona State

Inventors

• Ros Alexandra
• Kim Daihyun
• Luo Jinghui

Classifications

• B01L3/502715 Primary

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title

• B01L3/502753 Primary

  characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation · CPC title

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• B03C5/005

  Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength · CPC title

• B03C5/026

  using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC] · CPC title