Molecular entrapment and enrichment

Patent metadata

Field	Value
Publication number	US-9387488-B2
Application number	US-201213675735-A
Country	US
Kind code	B2
Filing date	Nov 13, 2012
Priority date	Nov 13, 2012
Publication date	Jul 12, 2016
Grant date	Jul 12, 2016

Abstract

Methods, structures, devices and systems are disclosed for rapid enrichment and mass transport of biomolecules (e.g., such as proteins) or other small molecules and particles using electrodeless dielectrophoresis (eDEP). In one aspect, a device to aggregate molecules includes a substrate that is electrically insulating, an electrically insulative material formed on the substrate and structured to form a channel to carry an electrically conducting fluid containing particles, a constriction structure formed of the electrically insulative material and located in the channel to narrow a channel dimension and forming an opening with a size in the nanometer range, and a circuit coupled to the substrate to apply an ac electric field and a dc bias electric field along the channel, in which the constriction structure is structured to magnify the applied ac electric field to produce forces that operate collectively to aggregate the particles.

First claim

What is claimed is:

1. A method for operating a device to aggregate particles in a fluid, comprising:
applying an ac electric field and a dc bias electric field along a channel in a device which includes:
a substrate that is electrically insulating;
an electrically insulative material formed on the substrate and structured to form the channel to carry an electrically conducting fluid containing particles; and
a constriction structure formed of the electrically insulative material and located in the channel to narrow a channel dimension and forming an opening with a size in the nanometer range; and
controlling the applied ac electric field and the dc bias electric field based on a structure of the constriction structure to magnify the applied ac electric field to produce a negative dielectrophoretic force (F NDEP ) in a direction away from the opening to combine with an electroosmotic force (F EO ) that is caused by the applied ac electric field with the dc bias to be in the direction away from the opening to counter an electrophoretic force (F EP ) in a direction toward the opening so that the F NDEP , F EO , and F EP operate collectively to aggregate the particles in an adjacent region on a side of the opening.

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

3. The method of claim 1 , wherein the particles include at least one of proteins, nucleic acids (DNA or RNA), peptides, or carbohydrates.

4. The method of claim 3 , wherein the proteins include a negative net charge and the adjacent region is on the negatively charged side of the dc bias.

5. The method of claim 1 , further comprising a sensor located along the channel to detect a parameter of the aggregated particles.

6. The method of claim 5 , wherein the sensor is an optical micrograph imager that detects an illumination intensity of the aggregated particles.

7. The method of claim 5 , wherein the sensor includes at least one of an electrical sensor, an electrochemical sensor, a mechanical sensor, or a magnetic sensor.

8. The method of claim 1 , wherein the circuit includes a gating electrode configured outside of an insulative layer provided by at least one of the channel or the substrate and located along the channel on a side of the constriction structure to provide an electrical charge used to affect the F EO .

9. The method of claim 1 , wherein the size of the opening is in a range of 5 to 500 nanometers.

10. The method of claim 1 , wherein the channel dimension is in a range of 100 nanometers to 1000 micrometers.

11. The method of claim 1 , wherein the channel dimension includes a width or a height.

12. The method of claim 11 , further comprising a first feeder channel and a second feeder channel having a channel width in a micrometer range or greater and formed of the electrically insulative material structured to carry the electrically conducting fluid, wherein the channel is located between and connected to the first feeder channel and the second feeder channel.

13. The method of claim 12 , further comprising fluidic reservoirs located along the first feeder channel and the second feeder channel and electrode terminals configured within the fluidic reservoirs and in contact with the fluid, wherein the ac electric field and the dc bias is applied along the channel across the electrode terminals.

14. The method of claim 12 , wherein the constriction structure magnifies by a field focusing factor based on (X micro /X nano )×(Z micro /Z nano )×(X nano /X c ) N, wherein X micro is the width of the feeder channel, X nano is the width of the channel, Z micro is the height of the feeder channel, Z nano is the height of the channel, X c is the width of the constriction structure, and N is a number of channels aligned in parallel between the first and second feeder channel.

15. The method of claim 1 , wherein the adjacent region is located away from heating spots caused by Joule effects.

16. The method of claim 1 , wherein the particles include an attached probe particle that enhance contrast of the particles due to a change in the size or the CM factor of the particles or response to an electric field gradient at the constriction structure.

17. A method for operating a device to characterize particles, comprising:
operating an electrodeless dielectrophoresis chip to carry an electrically conducting fluid containing particles, the chip including:
a substrate that is electrically insulating and structured to define a channel to carry the electrically conducting fluid,
a constriction structure of an electrically insulative material configured in the channel to narrow a dimension of the channel and forming an opening with a size in the nanometer range,
two microchannels formed of the electrically insulative material and having a channel width in a micrometer range or greater, wherein the channel is located between and connected to the two microchannels, and
fluidic reservoirs located along the two microchannels;

applying an ac electric field and a dc bias along the channel across electrode terminals configured within the fluidic reservoirs and in contact with the fluid to magnify the applied ac electric field to produce a negative dielectrophoretic force (F NDEP ) in a direction away from the opening;
controlling the applied ac electric field with the dc bias to produce an electroosmotic force (F EO ) in the direction away from the opening and an electrophoretic force (F EP ) in a direction toward the opening so that the F NDEP , F EO , and F EP combine to aggregate the particles in an adjacent region on a side of the opening; and
operating a characterization unit including a sensor positioned along the channel to detect a parameter of the aggregated particles and a processing unit to process the detected parameter as data to determine a characteristic of the particles.

18. The method of claim 17 , wherein the electrodeless dielectrophoresis chip further includes a gating electrode configured outside of an insulative layer provided by at least one of the channel or the substrate and located along the channel on a side of the constriction structure to provide an electrical charge used to affect the F EO .

19. The method of claim 1 , wherein the nanometer range size of the opening formed by the constriction structure in the channel is 30 nm or less.

20. The method of claim 1 , wherein the constriction structure includes a height of 220 nm or less.

21. The method of claim 1 , wherein the constriction structure includes a width of 30 nm or less.

22. The method of claim 1 , wherein the device is operable to aggregate the particles in the adjacent region on the side of the opening away from a gap region in the opening of the constriction structure.

23. The method of claim 1 , wherein the device is operable to aggregate the particles in the adjacent region on a single side of the opening of the constriction structure.

24. A method to operate a device to aggregate particles in a fluid, comprising:
applying an ac electric field and a dc bias electric field along a channel in a device which includes:
a substrate that is electrically insulating;
an electrically insulative material formed on the substrate and structured to form the channel to carry an electrically conducting fluid containing particles; and
a const

Assignees

• Academia Sinica

Inventors

• Chou Chia-Fu
• Liao Kuo-Tang

Classifications

• G01N15/0612

  Optical scan of the deposits (G01N15/0625 takes precedence) · CPC title

• B01L2400/0424

  Dielectrophoretic forces · 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

• B01L2400/086

  using baffles or other fixed flow obstructions · CPC title

• G01N27/44713

  Particularly adapted electric power supply · CPC title