Microfluidic systems and devices for molecular capture, manipulation, and analysis

Patent metadata

Field	Value
Publication number	US-9915614-B2
Application number	US-201313872013-A
Country	US
Kind code	B2
Filing date	Apr 26, 2013
Priority date	Apr 26, 2013
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

Methods, systems, and devices are disclosed for molecular capture, manipulation, and analysis. In one aspect, a device to aggregate and characterize particles in a fluid includes an electrically insulative substrate including a channel to carry an electrically conducting fluid containing particles, electrodes located in the channel forming a nanoscale opening and including an insulating layer over their surface at the opening, a first circuit to apply a non-uniform ac electric field and a dc bias signal across the electrodes, in which the applied non-uniform ac electric field produces a positive dielectrophoretic force to aggregate the particles in a trapping region including the opening and adjacent region, a second circuit to detect changes in a dc current caused by at least some of the particles in the trapping region, and an optical device that directs a coherent light beam on the opening to determine Raman spectra of the particles in the trapping region.

First claim

What is claimed is:

1. A device to capture and characterize particles in a fluid by combining sensing via electrical tunneling and coherent optical Raman sensing, comprising:
a substrate that is electrically insulating;
a channel formed of an electrically insulative material on the substrate and structured to carry an electrically conducting fluid containing particles;
a first electrode and a second electrode formed of an electrically conductive material and located in the channel to form an opening with a size in the nanometer range, each of the first and second electrodes structured to include a tip having an angle from 20 degrees to 120 degrees and including an electrically insulating layer over the electrode surface including at the opening between the electrodes;
a first circuit electrically coupled to the first and second electrodes to apply a non-uniform AC electric field and a DC bias signal across the first and second electrodes, wherein the applied non-uniform AC electric field produces a positive dielectrophoretic force (F PDEP ) in a direction towards the opening to capture a low quantity of the particles including 1,000 particles or fewer in a trapping region including the opening and in a region adjacent to the opening;
a second circuit coupled to the first and second electrodes to detect changes in a DC current produced by electrical tunneling through the opening and the electrically insulating layers over the electrode surfaces of the first and second electrodes based on operation of the applied DC bias signal and caused by at least some of the captured particles in the trapping region due to operation of the first circuit; and
an optical device including a laser to direct a coherent light beam on the opening and including a detector to detect inelastic scattering of the light beam by at least some of the captured particles in the trapping region due to operation of the first circuit to determine their Raman spectra.

2. The device as in claim 1 , wherein the first and second electrodes are structured to extend into the channel such that the electrodes narrow a channel dimension.

3. The device as in claim 1 , wherein the electrically insulative material includes at least one of glass, silica, oxidized silicon, silicon nitride, polysilsesquioxane (PSQ), polymethylmethacrylate (PMMA), or plastic.

4. The device as in claim 1 , wherein the particles include at least one of proteins, nucleic acids, peptides, carbohydrates, or nanoparticles.

5. The device as in claim 1 , wherein the size of the opening is in a range of 1 to 10 nanometers.

6. The device as in claim 1 , wherein the electrically insulating layer includes a native metal oxide coating.

7. The device as in claim 6 , wherein the native metal oxide coating includes titanium oxide.

8. The device as in claim 7 , wherein the titanium oxide coating is configured to have a thickness of 0.1 to 2 nanometers.

9. The device as in claim 1 , wherein the electrically insulating layer is formed of a self-assembled monolayer.

10. The device as in claim 1 , wherein the optical device is configured to detect an illumination intensity of the aggregated particles.

11. The device as in claim 10 , wherein the illumination intensity includes a fluorescence intensity.

12. The device as in claim 1 , further comprising a sensor located along the channel to detect a parameter of the captured particles, the sensor including at least one of an electrical sensor, an electrochemical sensor, a mechanical sensor, or a magnetic sensor.

13. The device as in claim 1 , wherein the second circuit includes a transimpedance amplifier.

14. A method to capture and characterize particles in a fluid k combining electrical sensing via electrical tunneling and optical sensing via coherent optical Raman spectroscopy, comprising:
receiving an electrically conducting fluid containing particles in a channel formed of an electrically insulative material and having a pair of electrodes to form an opening at an interface between the electrodes with a size in the nanometer range, wherein the electrodes are structured to include a tip having an angle from 20 degrees to 120 degrees and an electrically insulating layer over the electrode surface at the opening;
selecting a frequency and magnitude of an AC electric field and a bias magnitude of a DC electrical signal to be applied across the electrodes;
trapping a low quantity of the particles including 1,000 particles or fewer by applying the AC electric field to capture the particles in a trapping region including the opening and in a region adjacent to the opening;
detecting the captured particles by applying the DC electric signal across the electrodes to measure a current produced based on the presence of the particles in the trapping region via electrical tunneling through the opening and the electrically insulating layers over the electrode surfaces of the pair of electrodes;
directing a coherent light beam at the opening;
detecting, using an optical device including a detector, inelastic scattering of the light beam by at least some of the particles captured in the trapping region;
determining Raman spectra from the detected light; and
combining electrical sensing via the current based on electrical tunneling and optical sensing via the determined Raman spectra to measure the captured particles in the opening.

15. The method as in claim 14 , wherein the applied non-uniform AC electric field produces a positive dielectrophoretic force (F PDEP ) in a direction towards the opening to capture the particles in the trapping region.

16. The method as in claim 14 , wherein the particles include a first type of particles and a second type of particles.

17. The method as in claim 16 , further comprising selecting electrical parameters to separate the first type of particles from the second type of particles based on differences in polarizability and electrokinetic mobility of the first and second type of particles.

18. The method as in claim 17 , further comprising controlling the duration of the applied AC electric field to temporally control the separation of the first and second type of particles.

19. The method as in claim 14 , wherein the particles include at least one of proteins, nucleic acids, peptides, carbohydrates, or nanoparticles.

20. The method as in claim 14 , wherein the size of the opening is in a range of 1 to 10 nanometers.

21. The method as in claim 14 , wherein the electrically insulating layer includes a native metal oxide coating.

22. The method as in claim 21 wherein the native metal oxide coating includes titanium oxide and is configured to have a thickness of 0.1 to 2 nanometers.

23. The method as in claim 14 , wherein the electrically insulating layer is formed of a self-assembled monolayer.

24. A method to capture and characterize particles in a fluid by combining electrical sensing via electrical tunneling and optical sensing via coherent optical Raman spectroscopy, comprising:
receiving an electrically conducting fluid containing particles in a channel formed of an electrically insulative material and having a pair of electrodes to form an opening at an interface between the electrodes with a size in the nanometer range, wherein the electrodes are structured to include a tip having an angle from 20 degrees to 120 degrees and an electrically insulating layer over the electrode surface at the opening;
selecting a frequency and magnitude of a

Assignees

• Academia Sinica
• Max Planck Inst Fuer Eisenforschung Gmbh
• Max Planck Inst Fur Eisenforschung Gmbh

Inventors

• Chou Chia-Fu
• Leonardo Lesser-Rojas
• Chu Ming-Lee
• Erbe Andreas

Classifications

• 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

• G01N21/65 Primary

  Raman scattering · CPC title

• G01N33/48721

  Investigating individual macromolecules, e.g. by translocation through nanopores (Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68) · CPC title

• B03C2201/26

  for use in medical or biological applications · CPC title