Substance determining apparatus

Patent metadata

Field	Value
Publication number	US-9772272-B2
Application number	US-201013498615-A
Country	US
Kind code	B2
Filing date	Sep 24, 2010
Priority date	Sep 28, 2009
Publication date	Sep 26, 2017
Grant date	Sep 26, 2017

Abstract

A substance determining apparatus determines a substance within a fluid where particles, which have attached the substance, are bound to a binding surface. A sensing unit is configured to generate a sensing signal being indicative of at least one of i) a distance between the particles bound on the binding surface and the binding surface, and ii) an in-plane position of the particles bound on the binding surface. A binding discrimination unit is configured to discriminate between different kinds of binding of the particles bound on the binding surface depending on the generated sensing signal. The binding discrimination unit may be a unit for determining the part of the sensing signal being caused by specifically bound particles and for determining the substance based on this determined part of the sensing signal.

First claim

The invention claimed is:

1. A substance determining apparatus for determining a substance within a fluid, the substance determining apparatus comprising:
a binding device including a binding surface and particles configured to be attached to the substance within the fluid;
the binding surface being configured to bind the particles attached to the substance; and
an analyzing device including:
a sensor configured to:
sense the particles bound on the binding surface,
generate a sensing signal being indicative of at least one of i) a distance between the particles bound on the binding surface and the binding surface and ii) an in-plane position of the particles bound on the binding surface, wherein the sensor comprises a light source configured to generate radiation and direct the radiation to the binding surface, and wherein the radiation includes a first wavelength and a second wavelength;

a binding discrimination unit configured to discriminate between different kinds of binding of the particles bound on the binding surface depending on the sensing signal including light being scattered from the particles bound on the binding surface;
a display configured to display an indication of presence of the substance; and
a memory configured to store instructions that configure the analyzing device to determine the substance within a fluid by controlling at least one of the sensor, the binding discrimination unit and the display,
wherein the sensor is configured to:
modify at least one of i) the distance between the particles bound to the binding surface and the binding surface, ii) the in-plane position of the particles bound on the binding surface and iii) a distance sensitivity of the sensing unit, wherein the distance sensitivity is indicative of the dependence of the sensing signal on the distance between the particles bound to the binding surface and the binding surface,
generate a first sensing signal depending on at least one of i) a first distance between the particles bound to the binding surface and the binding surface, ii) a first in-plane position of the particles bound on the binding surface and iii) a first distance sensitivity, and
generate a second sensing signal depending on at least one of i) a second distance between the particles bound to the binding surface and the binding surface, ii) a second in-plane position of the particles bound to the binding surface and iii) a second distance sensitivity,

wherein the binding discrimination unit is configured to:
discriminate between the different kinds of the binding depending on the first sensing signal and the second sensing signal,
discriminate between the different kinds of the binding depending on a ratio of the first sensing signal and the second sensing signal,
determine a part of the sensing signal caused by specifically bound particles as a ratio having a numerator and a denominator and determine the substance based on the ratio, wherein the numerator is a difference between i) the first sensing signal and ii) a product of a non-specific ratio and the second sensing signal, and wherein the denominator is a difference between i) the first and ii) a ratio of the non-specific ratio and a specific ratio,
determine the specific ratio by generating the first sensing signal and the second signal while the substance is present in the fluid, and
determine the non-specific ratio by generating the first sensing signal and the second sensing signal while the substance is not present in the fluid.

2. The substance determining apparatus of claim 1 , wherein the radiation from the light source having the first wavelength and the second wavelength generates an evanescent field, and wherein the sensor further comprises a light detector configured to detect light from the binding surface and being indicative of an influence of the particles on the evanescent field, wherein the sensor is configured to:
generate the sensing signal based on the detected light,
modify the spatial relationship between the evanescent field and the particles bound to the binding surface by modifying at least one of i) the distance between the particles bound on the binding surface and the binding surface, ii) the in-plane position of the particles bound on the binding surface, and iii) the distance sensitivity,
generate the first sensing signal depending on a first spatial relationship between the evanescent field and the particles bound to the binding surface, and
generate the second sensing signal depending on a second spatial relationship between the evanescent field and the particles bound to the binding surface, and
wherein the light detector is configured to detect the light being scattered from the particles bound on the binding surface.

3. The substance determining apparatus of claim 1 , wherein the indication of presence of the substance includes one of and amount and a concentration of the substance within the fluid.

4. The substance determining apparatus of claim 1 , further comprising a magnetic unit configured to generate a rotating magnetic field for applying a force to the particles.

5. The substance determining apparatus of claim 4 , wherein the force is such that the particles are attracted towards the binding surface or pulled away from the binding surface.

6. The substance determining apparatus of claim 1 , wherein the sensor comprises a force applying unit configured to apply a force to the particles bound to the binding surface, wherein the sensor is configured to modify at least one of i) the distance between the particles bound to the binding surface and the binding surface and ii) the in-plane position of the particles bound on the binding surface by modifying the force applied to the particles bound on the binding surface.

7. The substance determining apparatus of claim 6 , wherein the force applying unit is configured to move the particles towards the binding surface and move the particles in a direction away from the binding surface, wherein the sensor is configured to generate a first detected signal if the particles bound to the binding surface have been moved towards the binding surface and generate a second detected signal if the particles bound to the binding surface have been moved in a direction away from the binding surface, and generate several detected signals over time while the particles bound to the binding surface are moved in a direction away from the binding surface, and wherein the binding discrimination unit is configured to discriminate between different kinds of binding depending on the several detected signals generated over time.

8. The substance determining apparatus of claim 6 , wherein the force applying unit is configured to use electrostatic forces to push particles bound to the binding surface away from the binding surface by exchanging the fluidic buffer in a fluidic wash step.

Assignees

• Evers Toon Hendrik
• Schleipen Johannes Joseph Hubertina Barbara
• Van Zon Joannes Baptist Adrianus Dionisius
• Klunder Derk Jan Wilfred
• Kahlman Josephus Arnoldus Hendricus Maria
• Van Lieshout Ron Martinus Laurentius
• Ovsyanko Mikhail Mikhaylovich
• Van Ommering Kim
• Koninklijke Philips Nv

Inventors

• Evers Toon Hendrik
• Schleipen Johannes Joseph Hubertina Barbara
• Van Zon Joannes Baptist Adrianus Dionisius
• Klunder Derk Jan Wilfred
• Kahlman Josephus Arnoldus Hendricus Maria
• Van Lieshout Ron Martinus Laurentius
• Ovsyanko Mikhail Mikhaylovich
• Van Ommering Kim

Classifications

• G01N21/552

  Attenuated total reflection · CPC title

• G01N35/0098

  involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation (magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C) · CPC title

• G01N21/648

  using evanescent coupling or surface plasmon coupling for the excitation of fluorescence · CPC title

• G01N2015/025

  Methods for single or grouped particles · CPC title

• G01N15/0612 Primary

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