Biomarker detection using integrated purification-detection devices

Patent metadata

Field	Value
Publication number	US-11033901-B2
Application number	US-201816168228-A
Country	US
Kind code	B2
Filing date	Oct 23, 2018
Priority date	Oct 23, 2018
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

Techniques regarding integrated purification-detection devices for detecting one or more biomarkers are provided. For example, one or more embodiments described herein are directed to an apparatus, comprising a housing and a microfluidic chip contained within the housing. The microfluidic chip comprises a separation unit that separates, using one or more nano deterministic lateral displacement (nanoDLD) arrays, target biological entities having a defined size range from other biological entities included in a biological fluid sample. The microfluidic chip further comprises a detection unit that facilitates detecting presence of one or more biomarkers associated with the target biological entities using one or more detection molecules or macromolecules that chemically reacts with the one or more biomarkers.

First claim

What is claimed is:

1. An apparatus, comprising:
a housing; and
a microfluidic chip contained within the housing, wherein the microfluidic chip comprises:
a separation unit comprising nanoscale deterministic lateral displacement arrays in fluid communication with an inlet bus formed around a perimeter of a first side of the nanoscale deterministic displacement arrays;

an outlet bus comprising an etched channel formed on a second side of the nanoscale deterministic displacement arrays opposite the first side within a thickness of the microfluidic chip, wherein the nanoscale deterministic displacement arrays are configured to laterally displace particles of interest comprised within a sample fluid supplied from the inlet bus and direct the particles of interest into the outlet bus; and
a detection unit configured for detecting presence of one or more biomarkers associated with the particles of interest using one or more detection molecules or macromolecules that chemically reacts with the one or more biomarkers, wherein the outlet bus surrounds the detection unit and supplies the particles of interest onto a sensing element surface of the detection unit coated with one or more detection molecules or macromolecules.

2. The apparatus of claim 1 , wherein the particles of interest comprise exosomes.

3. The apparatus of claim 1 , wherein the particles of interest have a diameter size from about 10.0 nanometers to about 200 nanometers.

4. The apparatus of claim 1 , wherein the one or more detection molecules or macromolecules comprise an antibody or aptamer that binds with a target epitope of the one or more biomarkers.

5. The apparatus of claim 1 , wherein the sensing element surface comprises a signal enhancing structure selected from a group consisting of a photonic grating structure, a photonic pillar array structure, an optoelectrical structure, and a plasmonic structure.

6. The apparatus of claim 1 , wherein the one or more detection molecules or macromolecules chemically react with the one or more biomarkers by binding to the one or more detection molecules or macromolecules, and wherein based on the binding, the one or more detection molecules or macromolecules generate a visual signal.

7. The apparatus of claim 6 , wherein a portion of the housing formed adjacent to the sensing element surface is transparent or partially transparent and enables visual observation of the visual signal.

8. The apparatus of claim 1 , wherein the detection unit further comprises:
an injection channel formed around a perimeter of the sensing element surface and in fluid communication with the outlet bus that uniformly supplies the particles of interest onto the sensing element surface.

9. The apparatus of claim 1 , wherein the detection unit further comprises:
at least one inlet via in fluid communication with the sensing element surface via which detection fluid comprising the one or more detection molecules or macromolecules is introduced onto the sensing element surface to coat the sensing element surface with the one or more detection molecules or macromolecules.

10. The apparatus of claim 1 , wherein the outlet bus supplies the particles of interest onto the sensing element surface within a stream of buffer fluid, and wherein the detection unit further comprises:
a central outlet located in a center region of the sensing element surface via which the buffer fluid, and unreacted portions of the target biological entities that fail to chemically react with the one or more detection molecules or macromolecules, are excreted from the detection unit.

11. The apparatus of claim 9 , wherein the detection unit further comprises:
a blocking element formed at an interface between the sensing element surface and the at least one inlet, wherein the blocking element inhibits reverse flow of one or more reacted molecular complexes from the sensing element surface through the at least one inlet, wherein the one or more reacted molecular complexes are formed as a result of a chemical reaction between the one or more detection molecules or macromolecules and the one or more biomarkers.

12. The apparatus of claim 1 , wherein the detection unit comprises two or more separate detection chambers, wherein respective chambers of the two or more separate detection chambers comprise different types of detection molecules or macromolecules of the one or more detection molecules or macromolecules, and wherein the different types of detection molecules or macromolecules chemically react with different types of biomarkers of the one or more biomarkers.

13. A method comprising:
isolating target particles having a defined size range from other particles included in a biological fluid sample using a separation unit comprising nanoscale deterministic lateral displacement arrays formed on a microfluidic chip in fluid communication with an inlet bus formed around a perimeter of a first side of the nanoscale deterministic displacement arrays;
collecting, as a result of the isolating, the target particles in an outlet bus comprising an etched channel formed on a second side of the nanoscale deterministic displacement arrays opposite the first side within a thickness of the microfluidic chip;
driving flow of a buffer fluid comprising the target particles from the outlet bus to a sensing element formed on the microfluidic chip, wherein the outlet bus surrounds the sensing element; and
facilitating detection of presence of one or more biomarkers associated with the target particles based on whether a detectable signal is generated at the sensing element in response to the driving.

14. The method of claim 13 , wherein the target particles comprise exosomes.

15. The method of claim 13 , wherein the sensing element comprises one or more detection molecules or macromolecules and wherein the detectable signal comprises a reaction signal that is indicative of a chemical interaction between the one or more detection molecules or macromolecules and the one or more biomarkers.

16. The method of claim 15 , wherein the chemical interaction is selected from a group consisting of: a covalent bonding reaction, an electrostatic interaction, a hydrophobic interaction, an antibody-epitope interaction, an aptamer-epitope reaction, a protein-protein interaction, a protein-small molecule interaction, a polymerization reaction, a complementarity reaction, a complementary deoxyribonucleic acid (DNA) strand hybridization interaction, and a complementary ribonucleic acid (RNA) strand hybridization interaction.

17. The method of claim 15 , wherein the method further comprises:
prior to the driving, functionalizing a surface of the sensing element with the one or more detection molecules or macromolecules, wherein the functionalizing comprises injecting a solution comprising the one or more detection molecules or macromolecules into a chamber enclosing the surface of sensing element via at least one injection inlet of the microfluidic chip.

18. The method of claim 13 , wherein the detectable signal comprises a visual signal and wherein the method further comprises:
determining whether the detectable signal is generated using a microscope positioned adjacent the sensing element.

19. The method of claim 13 , wherein the detectable signal comprises a visual signal and wherein the method further comprises:
capturing, by a device operatively coupled to a processor, image data of the sensing element in association with the driving; and
determining, by the device, whether the visual signal is generated based o

Assignees

• IBM

Inventors

• Smith Joshua T
• Wunsch Benjamin
• Gifford Stacey
• Kim Sung-Cheol

Classifications

• B01L2300/0896

  Nanoscaled · CPC title

• B01L2200/0663

  Stretching or orienting elongated molecules or particles · CPC title

• B01L2300/0654

  Lenses; Optical fibres · CPC title

• B01L2300/0877

  Flow chambers · CPC title

• B01L3/502753 Primary

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