NANOFLUIDIC CELL

• US 20120182548A1
• Filed: 07/23/2010
• Published: 07/19/2012
• Est. Priority Date: 07/23/2009
• Status: Abandoned Application

• Current Assignee: Insight Nanofluidics Inc.
• Original Assignee: Insight Nanofluidics Inc.
• Inventors: Harb, Maher, Paarmann, Alex, Dwyer, Jason, Miller, Dwayne R. J.
• Application Number:
  US13/386,567
• Publication Number:
  US 20120182548A1
• Time in Patent Office: Days
• US Class Current: 356/246
• CPC Class Codes: B82Y 35/00 Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 2223/637 liquid
• CPC Class Codes: G01N 2291/02466 Biological material, e.g. blood
• CPC Class Codes: G01N 2291/048 Transmission, i.e. analysed material between transmitter and receiver
• CPC Class Codes: G01N 29/032 by measuring attenuation of acoustic waves
• CPC Class Codes: G01N 29/222 Constructional or flow details for analysing fluids optoacoustic fluid cells G01N29/2425
• CPC Class Codes: H01J 2237/2003 Environmental cells
• CPC Class Codes: H01J 2237/2004 Biological samples
• CPC Class Codes: H01J 37/20 Means for supporting or positioning the object or the material; Means for adjusting diaphragms or lenses associated with the support

Abstract

A flow cell is provided for the analysis and/or microscopy of liquid or gas samples on the nanometer to micron scale. The flow cell preferably includes a thin membrane that is transparent to electrons and/or photons, thereby enabling the penetration of electrons or photons into a liquid flowing through the cell. Trenches are provided on either side of the membrane, which advantageously minimize fluidic resistance outside of the window area of the cell and also enable a faster response time in response to changes in external fluidic pressure. This feature enables active feedback using pathlength sensitive probes to stabilize the fluid flow to thin streams from nanometer to micron scale thicknesses with nanometer precision.

Claims

1. A flow cell comprising:

a body structure comprising an internal channel, an inlet port and an outlet port, wherein said inlet port and said outlet port are in flow communication with said internal channel;

said body structure further comprising a membrane enclosing a portion of said internal channel and defining a detection zone within said internal channel, wherein a thickness of said membrane is selected to allow the transmission of a probe beam within a selected energy range through said membrane and into said internal channel; and

wherein transverse dimensions of said internal channel outside of said detection zone are selected to provide a fluidic resistance outside of said detection zone that is less than a fluidic resistance within said detection zone.

2. The flow cell according to claim 1 wherein a thickness of said internal channel within said detection zone is on a micron to submicron scale.

4. The flow cell according to claim 1 wherein said thickness of said membrane is on a nanometer scale.

7. The flow cell according to claim 1 wherein said internal channel further comprises trenches provided adjacent to said detection zone, wherein said trenches comprise transverse dimensions that are selected to provide a fluidic resistance outside of said detection zone that is less than a fluidic resistance within said detection zone.

9. The flow cell according to claim 1 wherein said probe beam is selected from the group consisting of an optical beam, an x-ray beam, and an electron beam.

11. The flow cell according to claim 1 wherein said membrane is a first membrane and wherein said body structure further comprises a second membrane on an opposing side of said internal channel within said detection zone, and wherein a thickness of said membrane is selected to allow the transmission of said probe beam through said membrane.

12. The flow cell according to claim 1 wherein said membrane comprises a material selected form the group consisting of silicon nitride, boron nitride, silicon carbide, silicon, silicon dioxide, carbon, diamond and other allotropes of carbon, molybdenum disulphide and graphene.

15. The flow cell according to claim 1 wherein said body structure includes:

a first substrate having a transparent layer provided on a surface thereof, wherein said transparent layer is transparent to said probe beam within a selected energy range;

an aperture formed in said first substrate, said aperture extending through said first substrate and exposing said membrane, said membrane forming a portion of said transparent layer;

a second substrate;

a spacer layer contacting said transparent layer and a surface of said second substrate, said spacer layer having provided therein an opening defining said internal channel, said internal channel in flow communication with said membrane within a detection zone of said internal channel, wherein said inlet port and said outlet port are provided in one of said first substrate and said second substrate; and

first and second trenches provided on adjacent sides of said detection zone within one of said first substrate and said second substrate, said trenches contacting said internal channel for increasing a thickness of said internal channel on either side of said detection zone;

wherein transverse dimensions of said trenches are selected to provide a fluidic resistance outside of said detection zone that is less than a fluidic resistance within said detection zone.

17. The flow cell according to claim 15 wherein said transparent layer comprises a material selected form the group consisting of silicon nitride, boron nitride, silicon carbide, silicon, silicon dioxide, carbon, diamond and other allotropes of carbon, molybdenum disulphide and graphene.

23. The flow cell according to claim 15 wherein said transparent layer is a first transparent layer and said aperture is a first aperture, and wherein said second substrate has a second transparent layer provided on a surface thereof, said second transparent layer contacting said spacer layer, wherein said second transparent layer is transparent to said probe beam within said selected energy range, and wherein said body structure further comprises a second aperture formed in said second substrate, said second aperture comprising an aperture extending through said second substrate and exposing a second membrane comprising a portion of said second transparent layer, and wherein said first aperture is aligned with said second aperture for the transmission of said probe beam through said flow cell.

26. The flow cell according to claim 15 wherein said spacer layer is formed from a material selected from the group consisting of silicon dioxide, polycrystalline silicon, amorphous silicon, photoresist, Teflon™

and titanium.

28. A system for controlling a thickness of an internal channel within a flow cell, said system comprising:

a flow cell according to claim 1;

a flow means for flowing a sample to said inlet port and removing said sample from said outlet port;

means for detecting a signal related to said thickness of said internal channel; and

a processing and control means for controlling said flow means in response to said signal for controlling said thickness of said internal channel.

29. An electron microscope system adapted for the analysis of a fluid sample within a fluidic cell, said system comprising:

an electron microscope comprising a chamber;

a flow cell according to claim 1, wherein said flow cell is provided within said chamber; and

a flow means for flowing said sample to said inlet port and removing said sample from said outlet port.

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6. The flow cell according to 1 wherein an area of said membrane is less than approximately 1 mm².

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31. A method of analyzing a fluid sample with a flow cell, said flow cell comprising:

a body structure comprising an internal channel, an inlet port and an outlet port, wherein said inlet port and said outlet port are in flow communication with said internal channel;

said body structure further comprising a membrane enclosing a portion of said internal channel and defining a detection zone within said internal channel, wherein a thickness of said membrane is selected to allow the transmission of a probe beam within a selected energy range through said membrane and into said internal channel; and

wherein transverse dimensions of said internal channel outside of said detection zone are selected to provide a fluidic resistance outside of said detection zone that is less than a fluidic resistance within said detection zone;

the method comprising the steps of;

flowing said sample to said inlet port and through said internal channel;

directing said probe beam onto said membrane; and

detecting one of a reflected probe beam and a transmitted probe beam.

36. The method according to claim 31 wherein a thickness of said internal channel is actively controlled by:

detecting a signal related to said thickness of said internal channel;

processing said signal to obtain a feedback parameter related to a difference between a thickness of said internal channel and a desired thickness of said internal channel; and

controlling flow of said sample to optimize said feedback parameter.

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43. A method for fabricating a flow cell, comprising the steps of:

a) providing an upper substrate;

b) depositing a transparent layer onto a bottom surface of said upper substrate, wherein said transparent layer is transparent to a probe beam within a selected energy range;

c) forming an aperture within said upper substrate, said aperture extending through said upper substrate, by removing a portion of said upper substrate and exposing a membrane comprising a portion of said transparent layer;

d) providing a lower substrate;

e) depositing a spacer layer onto one of said transparent layer of said upper substrate and an upper surface of said lower substrate, and removing a portion of said spacer layer to define a channel;

e) forming an inlet port and an outlet port in one of said upper substrate and said lower substrate;

f) forming first and second trenches provided on adjacent sides of said membrane within one of said upper substrate and said lower substrate; and

g) aligning and adhering said upper substrate and said lower substrate;

wherein said membrane defines a detection zone within said channel; and

wherein said channel is in flow communication with said membrane, said trenches, said inlet port and said outlet port for flowing a sample through said detection zone within said flow cell, and wherein said trenches comprise transverse dimensions selected to provide a fluidic resistance outside of said detection zone that is less than a fluidic resistance within said detection zone.

44. The method according to claim 43, wherein said aperture is a first aperture, the method further comprising the steps of:

after performing step (d), providing a second transparent layer on a top surface of said lower substrate, wherein said second transparent layer is transparent to said probe beam; and

forming a second aperture within said lower substrate, said second aperture extending through said lower substrate, by removing a portion of said lower substrate and exposing a second membrane comprising a portion of said second transparent layer;

wherein when said upper substrate is aligned and adhered with said lower substrate, said first aperture is aligned with said second aperture.

45. The method according to claim 43 wherein said transparent layer comprises a material selected form the group consisting of silicon nitride, boron nitride, silicon carbide, silicon, silicon dioxide, carbon, diamond and other allotropes of carbon, molybdenum disulphide and graphene.

46. The method according to claim 43 wherein said spacer layer is formed from a material selected form the group consisting of silicon dioxide, polycrystalline silicon, amorphous silicon, photoresist, Teflon™

and titanium.

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