Substance determining apparatus

Patent metadata

Field	Value
Publication number	US-9612239-B2
Application number	US-201214001566-A
Country	US
Kind code	B2
Filing date	Feb 27, 2012
Priority date	Feb 28, 2011
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

The invention relates to a substance determining apparatus ( 19 ) for determining a substance within a fluid. A location event determination unit ( 34 ) determines location events indicating that a particle, which may have attached the substance, is located in a sensing region and a property of the location events from the sensing signal generated by sensing the sensing region. A location events selection unit ( 70 ) selects a part of the location events having a property in a predefined property range, and a substance determination unit ( 40 ) determines the substance within the fluid ( 3 ) based on the selected part of the location events. This allows tuning the determination of the substance within the fluid to a desired property range, which can relate to a desired kind of bound particles, thereby reducing the influence of unwanted effects on the determination of the substance and, thus, improving the determination accuracy.

First claim

The invention claimed is:

1. A substance determining apparatus for determining a substance within a fluid, the substance determining apparatus comprising:
particles configured to bind to the substance within the fluid,
a binding surface to which the particles are configured to bind if the particles have been attached to the substance,
a sensor configured to sense the particles within a sensing region on the binding surface, wherein the sensor is adapted to generate a sensing signal depending on the particles in the sensing region, and
computing hardware programmed to perform a substance determining method including:
determining location events indicating that a particle is located in the sensing region on the binding surface and lifetimes of the location events from the sensing signal generated by the sensor,
selecting a part of the location events having a lifetime in a predefined lifetime range, and
determining the substance within the fluid based on the selected part of the location events.

2. The substance determining apparatus as defined in claim 1 , wherein the substance determining method further determines at least one of the following properties of the respective location event: starting moment, ending moment, size, and positional variation of the respective particle in the sensing region.

3. The substance determining apparatus as defined in claim 1 , wherein the substance determining method further determines several properties of a respective location event and the selecting comprises selecting a part of the location events having all said several properties within respective property ranges.

4. The substance determining apparatus as defined in claim 2 , wherein the generated sensing signal is indicative of starting moments and ending moments of location events and wherein the determining of location events includes determining the lifetimes of location events by determining the starting moments and the ending moments of the location events from the generated sensing signal.

5. The substance determining apparatus as defined in claim 2 , wherein the sensor comprises an imaging unit configured to generate images of the binding surface at different times as the sensing signal, wherein an image shows at which positions on the binding surface particles are located at a time, wherein the at least one of the following properties of the respective location event:
the starting moment by comparing temporally consecutive images,
the ending moment by comparing temporally consecutive images,
the size of a respective location event in the respective images, and
the positional variation of the respective particle in the sensing region by tracking the respective particle in temporally consecutive images.

6. The substance determining apparatus as defined in claim 5 , wherein the sensor comprises:
a light source arranged to generate radiation directed to the binding surface for generating an evanescent field, which defines the sensing region; and
a light detector arranged to detect light from the binding surface, wherein the detected light has been influenced by the particles located on the binding surface by influencing the evanescent field and wherein the images are generated from the detected influenced light.

7. The substance determining apparatus as defined in claim 1 , wherein the sensor comprises a force applying unit for applying a force to the particles for putting bindings between the particles and the binding surface under stress, while sensing the particles.

8. The substance determining apparatus as defined in claim 7 , wherein the determining of location events includes:
determining a particles signal being indicative of the number of particles in the sensing region from the sensing signal,
differentiating the particles signal, and
determining a distribution of location events depending on their lifetime in the sensing region from the differentiated particles signal,
wherein the selecting includes selecting the part of the location events having a lifetime within a predefined lifetime range being the predefined property range based on the determined distribution of location events.

9. The substance determining apparatus as defined in claim 1 , wherein the predefined lifetime range is predefined such that a figure of merit, which is indicative of a ratio of a specific histogram of lifetimes of specific location events being binding events, which relate to bindings of particles having been attached to the substance, and a non-specific histogram of lifetimes of non-specific location events, which relate to other location events, has an optimum within the predefined lifetime range.

10. The substance determining apparatus as defined in claim 1 , wherein the predefined lifetime range is predefined such that a probability that the lifetime of location events, which are related to at least one of unbound particles, other elements and artifacts on the binding surface, is not within the predefined lifetime range is larger than a probability that lifetimes of location events, which are related to at least one of unbound particles, other elements and artifacts on the binding surface, is within the predefined lifetime range.

11. The substance determining apparatus as defined in claim 1 , wherein the computing hardware comprises a computer configured to perform the substance determining method.

Assignees

• Van Zon Joannes Baptist Adrianus Dionisius
• Evers Toon Hendrik
• Van Lieshout Ron Martinus Laurentius
• Hardeman Wilhelmina Maria
• Klunder Derk Jan Wilfred
• Koninklijke Philips Nv

Inventors

• Van Zon Joannes Baptist Adrianus Dionisius
• Evers Toon Hendrik
• Van Lieshout Ron Martinus Laurentius
• Hardeman Wilhelmina Maria
• Klunder Derk Jan Wilfred

Classifications

• G01N21/552 Primary

  Attenuated total reflection · CPC title

• G01N33/54326 Primary

  Magnetic particles · CPC title

• G01N21/648

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

• G01N27/745

  for detecting magnetic beads used in biochemical assays (concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098) · CPC title

• G01N21/7703

  using reagent-clad optical fibres or optical waveguides (using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B) · CPC title