Sensing device and manufacturing method thereof

Patent metadata

Field	Value
Publication number	US-9534250-B2
Application number	US-201113095790-A
Country	US
Kind code	B2
Filing date	Apr 27, 2011
Priority date	Apr 30, 2010
Publication date	Jan 3, 2017
Grant date	Jan 3, 2017

Abstract

The present invention relates to a sensing device with a surface having at least one individual sensing region, wherein each sensing region includes a plurality of binding elements anchored on the surface for binding different specific analytes of interest, at least one of the analyte of interest and its matching binding element having a label for detecting said binding. The present invention further relates to a method of manufacturing such a sensing device.

First claim

The invention claimed is:

1. A sensing device comprising:
a substrate having a surface and having a plurality of individual sensing regions on said surface,
wherein each said sensing region includes a plurality of different length binding elements anchored on said surface for binding different specific analytes of interest, at least one of the specific analytes of interest and its matching binding element having a label for detecting said binding based on time-dependent variations in a signal caused by tethered particle motion.

2. The sensing device of claim 1 , wherein each said binding element is unique and configured and arranged to exhibit different molecular dynamic behavior, and wherein the signal is radiated as an electrical or optical signal.

3. The sensing device of claim 1 , wherein the binding elements on each said sensing region comprise different length biological molecules chemically bound on said surface.

4. The sensing device of claim 1 , wherein the binding elements on each said sensing region comprise biological molecules anchored on said surface by different length spacer molecules.

5. The sensing device of claim 3 , wherein the respective biological molecules comprise a nucleotide chain and wherein each of said binding elements has a nucleotide sequence complementary to the nucleotide sequence of one of the biological molecules such that the binding element is configured and arranged to bind the biological molecule.

6. The sensing device of claim 1 , wherein the label comprises a bead, wherein each label is a similar size and is configured and arranged to scatter incident electromagnetic radiation.

7. The sensing device of claim 1 , further comprising a detection circuit configured and arranged to detect binding of a specific analyte of interest to its matching binding element.

8. The sensing device of claim 7 , wherein the sensing device includes an integrated circuit, said sensing regions being arranged on a surface of said integrated circuit, wherein the detection circuit forms part of the integrated circuit and includes a plurality of circuit elements respectively coupled to the sensing regions for electrically detecting the binding of a specific analyte of interest to its matching binding element and the detection circuit and plurality of circuit elements are further configured and arranged to distinguish between binding events occurring on the same sensing region based on the time-dependent variations in the signal caused by tethered particle motion.

9. The sensing device of claim 7 , wherein the detection circuit comprises an optical element configured and arranged to optically detect the binding of a specific analyte of interest to its matching binding element and to distinguish between binding events occurring on the same sensing region based on the time-dependent variations in the signal caused by differences in tethered particle motion, wherein the differences in the tethered particle motion are correlated to an overall length of respective analytes of interest bound to their respective matching binding element.

10. An apparatus comprising the sensing device of claim 1 , and an output circuit configured and arranged to provide a sensing result to a user of said apparatus.

11. A method of manufacturing a sensing device comprising a substrate having a surface and having a plurality of individual sensing regions on said surface, the method comprising, for each said sensing region, the steps of:
providing a droplet on said sensing region, said droplet having a plurality of different length binding elements for binding different specific analytes of interest; and
anchoring said different length binding elements on the surface of said sensing region wherein each binding element comprises a label for detecting the binding of the corresponding specific analyte of interest to said binding element based on time-dependent variations in a signal caused by tethered particle motion.

12. The method of claim 11 , wherein the sensing device includes an integrated circuit, and wherein the label further for distinguishing between binding events occurring on the same sensing region based on the time-dependent variations in the signal caused by tethered particle motion.

13. The method of claim 11 , wherein the binding elements on each sensing region comprise biological molecules having a different nucleotide chain length.

14. The method of claim 11 , wherein said anchoring step comprises anchoring respective biological molecules on said surface using different length spacer molecules.

15. The method of claim 13 , wherein the biological molecules and the plurality of different length binding elements each comprise a nucleotide sequence, the nucleotide sequence of each binding element being complementary to the nucleotide sequence of one of the specific biological molecules such that the binding element is configured and arranged to bind the specific biological molecule.

16. The method of claim 11 , wherein said anchoring step comprises chemically binding said binding elements on the surface of said sensing region.

17. The sensing device of claim 8 , wherein the detection circuit and the plurality of circuit elements are configured and arranged to detect a variation in the signal generated by the sensing region at which a binding event occurs.

18. The sensing device of claim 17 , wherein the variation in the signal is correlated with the chain length of the specific biological molecule bound by the binding element.

19. The sensing device of claim 17 , wherein the detection circuit and the plurality of circuit elements are configured and arranged to distinguish between binding events occurring on the same sensing region by analyzing the time-dependent variation in the signal.

20. The sensing device of claim 1 , wherein the sensing device includes an integrated circuit having the surface, said sensing regions being arranged on the surface of said integrated circuit, and wherein the binding elements on each said sensing region comprise different length biological molecules chemically bound on said surface, the sensing device further comprising:
a detection circuit configured and arranged to detect binding of a specific analyte of interest to its matching binding element, wherein the detection circuit forms part of the integrated circuit and includes a plurality of circuit elements respectively coupled to the sensing regions and configured and arranged to electrically detect the binding of a specific analyte of interest to its matching binding element, and
wherein the detection circuit and the plurality of circuit elements are configured and arranged to detect a variation in a signal generated by the sensing region at which a binding event occurs, and to distinguish between binding events occurring on the same sensing region by analyzing a time-dependent variation in the signal.

Assignees

• Van Steenwinckel David
• Frederix Filip
• Nxp Bv

Inventors

• Van Steenwinckel David
• Frederix Filip

Classifications

• B01J2219/00722

  Nucleotides · CPC title

• C40B60/12

  for screening libraries · CPC title

• C12Q1/6837 Primary

  using probe arrays or probe chips (C12Q1/6874 takes precedence) · CPC title

• B01J2219/00576

  fluorophore · CPC title

• C12Q2565/607

  being a sensor, e.g. electrode · CPC title