Concentration measurement using luminescence

• US 9,207,176 B2
• Filed: 07/19/2011
• Issued: 12/08/2015
• Est. Priority Date: 07/19/2010
• Status: Active Grant

• Current Assignee: Oxford Optronix Ltd.
• Original Assignee: Oxford Optronix Ltd.
• Inventors: Ward, Geoffrey
• Primary Examiner(s): TANINGCO, MARCUS H
• Application Number:
  US13/811,182
• Publication Number:
  US 20130256562A1
• Time in Patent Office: 1,603 Days
• Field of Search: 250/459.1
• US Class Current: 1/1
• CPC Class Codes: G01N 2021/641 Phosphorimetry, gated
• CPC Class Codes: G01N 2021/6413 Distinction short and delayed fluorescence or phosphorescence
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/772 Tip coated light guide
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/7703 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

Abstract

A method of measuring the concentration of a substance, using a sensor (2) comprising a luminescent material, an LED light source (14) which supplies a pulse of light to the sensor to cause luminescence of the material, a detector (26) for detecting the emitted light and a data processing module (28) for analysing the signals and indicating the concentration of the substance. In a measuring sequence there is a series of pulses of light spaced apart sufficiently to permit the luminescence to decay between pulses. The signals which are analysed are those generated after each pulse of light has terminated and the luminescence is decaying. The data processing module (28) comprises a plurality of accumulators (52A, 52B, 52C and 52D) which are controlled to be operable over a corresponding plurality of different periods of time during decay of the luminescence. Each accumulator accumulates values indicative of the intensity of the luminescence from the series of pulses in the measuring sequence. The parameters regarding the accumulators are stored in a configuration memory (42) which is part of the sensor.

Claims

1. A method of measuring the concentration of a substance, using a sensor comprising a luminescent material having a luminescent activity whose characteristics depend on the concentration of the substance, a light source which supplies a pulse of light to the sensor for a period of time sufficient to cause corresponding luminescence of the luminescent material, the luminescence rising to a peak and then decaying after the end of the pulse of light, a detector for detecting the light emitted by the luminescence of the luminescent material and generating signals in response thereto, and a data processing module for analyzing the signals and for providing data indicative of the concentration of the substance;

wherein in a measuring sequence there is a series of pulses of light spaced apart sufficiently to permit the luminescence corresponding to each pulse in the measuring sequence to decay between pulses, the signals which are analyzed to provide the data indicative of the concentration of the substance are those generated after each pulse of light has terminated and the corresponding luminescence is decaying,

wherein the data processing module comprises a plurality of accumulators which are controlled to be operable over a corresponding plurality of different periods of time during the decay of the luminescence,

wherein in an acquisition phase of the measuring sequence each accumulator accumulates intensity values indicative of the intensity of the luminescence corresponding to each of the series of pulses in the measuring sequence by adding the intensity value corresponding to one pulse to the accumulated values corresponding to previous pulses, and

wherein the measuring sequence further comprises read phase in which the values accumulated in the accumulators are read and a reset phase after the acquisition and read phases in which the accumulators are reset.

2. A method as claimed in claim 1, wherein for each accumulator the accumulator value is sampled at intervals during the measuring sequence, and the values are processed to provide a slope which is used in determination of the substance concentration.

3. A method as claimed in claim 1, wherein the data processing module comprises two channels, each of which comprises a plurality of said accumulators which are controlled to be operable over a corresponding plurality of different periods of time during decay of the luminescence, each accumulator accumulating values indicative of the intensity of the luminescence from the series of pulses in the measuring sequence;

and wherein the measuring sequences are alternated between the two channels, the accumulators in one channel being reset after the end of the measuring sequence using that channel, while a measuring sequence is carried out using the other channel.

4. A method as claimed in claim 1, wherein there are at least four accumulators, controlled to be operable over a corresponding number of different periods during the decay of the luminescence.

5. A method as claimed in claim 3 wherein in each channel there are at least four accumulators, controlled to be operable over a corresponding number of different periods during the decay of the luminescence.

6. A method as claimed in claim 1, wherein there are first and second accumulators which are timed to be active while the luminescence is decaying relatively steeply, the first accumulator being active over a first period of time and the second accumulator being active over an adjacent period of time which commences on, or a relatively short time after, the end of the first period of time.

7. A method as claimed in claim 6, wherein there is a third accumulator which is active over a third period of time, which commences a relatively long time after the end of the second period of time, when there is a substantially less steep rate of decay of the luminescence than during the first and second periods of time.

8. A method as claimed in claim 7, wherein there is a fourth accumulator which is active over a fourth period of time, which commences a relatively long time after the end of the third period of time.

9. A method as claimed in claim 1, wherein each accumulator is operable for a period which is less than 5 microseconds during the decay of the luminescence.

10. A method as claimed in claim 1, wherein the periods of time over which the respective accumulators are operable are of substantially equal duration.

11. A method as claimed in claim 1, wherein the periods over which the respective accumulators are active are determined by configuration parameters stored in a configuration memory.

12. A method as claimed in claim 11, wherein the configuration parameters are stored in a configuration memory which is part of the sensor, and when the sensor is connected to the control unit, a connection is made with the configuration memory, and the configuration parameters are read and used by the data processing module.

13. A method as claimed in claim 12, wherein the configuration memory which is part of the sensor stores, in addition to the configuration parameters, any or all of the energy and/or time exposure of the sensor;

the allowed amount of energy or time exposure;

the date of calibration of the sensor;

the allowed period of time from the date of calibration of the sensor;

the date of first use of the sensor;

the allowed period of time from the date of first use of the sensor;

the number of times that the sensor has been used;

the allowed number of times that the sensor may be used;

sensor identification information;

sensor configuration information;

the units of measurement for the assay substance;

light pulsing and accumulator timings;

minimum and maximum acceptable luminescent lifetimes;

minimum and maximum acceptable sensor temperatures;

minimum and maximum acceptable assay concentrations; and

sensor dye and temperature calibration information.

14. Apparatus for measuring the concentration of a substance, comprising a sensor comprising a luminescent material having a luminescent activity whose characteristics depend on the concentration of the substance, a light source which supplies a pulse of light to the sensor for a period of time sufficient to cause corresponding luminescence of the luminescent material, the luminescence rising to a peak and then decaying after the end of the pulse of light, a detector for detecting the light emitted by the luminescence of the luminescent material and generating signals in response thereto, and a data processing module for analyzing the signals and for providing data indicative of the concentration of the substance;

wherein the data processing module is configured so that in a measuring sequence there is a series of pulses of light spaced apart sufficiently to permit the luminescence corresponding to each pulse in the measuring sequence to decay between pulses, the signals which are analyzed to provide the data indicative of the concentration of the substance are those generated after each pulse of light has terminated and the corresponding luminescence is decaying,

wherein the data processing module comprises a plurality of accumulators which are controlled to be operable over a corresponding plurality of different periods of time during decay of the luminescence,

wherein in an acquisition phase of the measuring sequence each accumulator accumulates intensity values indicative of the intensity of the luminescence corresponding to each of the series of pulses in the measuring sequence by adding the intensity value corresponding to one pulse to the accumulated values corresponding to previous pulses, and

wherein the measuring sequence further comprises a read phase in which values accumulated in the accumulators are read and a reset phase after the acquisition and read phases in which the accumulators are reset.

15. A method of measuring a concentration of a substance, using a sensor comprising a luminescent material having a luminescent activity whose characteristics depend on the concentration of the substance, wherein there is a measuring sequence having an acquisition phase and a reset phase;

during the acquisition phase a light source supplies a series of pulses of light to the sensor, each pulse of light causing a luminescence event in which there is luminescence of the luminescent material, the luminescence decaying over time after the pulse of light has ceased;

there being a detecting system which detects light emitted by the luminescent material during each luminescence event and generates signals indicative of the intensity of the luminescence;

wherein

there is a plurality of accumulators which are controlled to be operable over a corresponding plurality of different periods of time during the decay of the luminescence in each luminescence event in the acquisition phase;

in respect of a first luminescence event in the acquisition phase, each accumulator receives and stores a value representing the intensity of the luminescence over the respective period of time for which the accumulator is operable;

in respect of a second luminescence event in the acquisition phase, each accumulator receives a second value representing the intensity of the luminescence over the respective period of time for which the accumulator is operable, which second value is added to the first value stored in the accumulator so as to provide an accumulated value stored in the accumulator;

in respect of each subsequent luminescence event in the acquisition phase, each accumulator receives a further value representing the intensity of the luminescence over the respective period of time for which the accumulator is operable, which further value is added to the existing stored value in the accumulator so as to provide a revised accumulated value;

at intervals in the acquisition phase the accumulated value in each accumulator is sampled;

for each accumulator the sampled values are processed to provide a slope;

after the acquisition phase there is a reset phase of the measuring sequence, in which the accumulators are reset; and

wherein the substance concentration is determined using the slopes provided in the acquisition phase.

16. A method according to claim 15, wherein after the acquisition phase and the reset phase there is a further measuring sequence.

17. A method according to claim 15, wherein each sampled accumulated value is stored together with a state value indicating where in the measuring sequence the sample was taken.

18. A method according to claim 15, wherein the number of pulses in the series of pulses during the acquisition phase is of the order of thousands.

19. A method according to claim 18, wherein the accumulators are provided in a data processing module which comprises two channels, each of which comprises a plurality of said accumulators;

and wherein the measuring sequences are alternated between the two channels, the accumulators in one channel being reset after the end of the measuring sequence using that channel, while another measuring sequence is carried out using the other channel.