WO2016060543A1 - A system and method to extract phase shift of a fluorescence signal - Google Patents
A system and method to extract phase shift of a fluorescence signal Download PDFInfo
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- WO2016060543A1 WO2016060543A1 PCT/MY2015/050059 MY2015050059W WO2016060543A1 WO 2016060543 A1 WO2016060543 A1 WO 2016060543A1 MY 2015050059 W MY2015050059 W MY 2015050059W WO 2016060543 A1 WO2016060543 A1 WO 2016060543A1
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- voltage signal
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6408—Fluorescence; Phosphorescence with measurement of decay time, time resolved fluorescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/12—Circuits of general importance; Signal processing
- G01N2201/124—Sensitivity
Definitions
- the photo detector (50) converts the fluorescence signal, Y(t) to electrical current signal and thereon, the photo detector (50) mixes the electrical current, Y(t) with either the in-phase signal, X(t) or the quadrature signal, X q (t). The resulted mixed signal of X(t) and Y(t) or X q (t) and Y(t) is then routed through the LPF (70). Thus, the photo detector (50) is connected to the RF switch (60) and the LPF (70).
- the FGU (10) generates the known in-phase signal, X,(t), and supplies the known in-phase signal, X,(t), to the LED (20) as in step 200.
- the in-phase signal is also supplied to the phase shifter (40) and the RF switch (60).
- the result of the multiplication is then routed through the LPF (70) to remove the high order mixing products.
- the multiplied signal is further converted by the TIA (80) from current to in-phase voltage signal, Vj(t). Thereon, the in-phase voltage signal, V,(t), is stored in a digital processor.
- phase shift information denotes the amount of specimen present in a medium as being sensed by the sensor element (30) such as the concentration level of dissolved oxygen or dissolved ammonia.
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- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The present invention relates to a system (100) and method to extract phase shift of fluorescence signal. The system (100) comprises of a Frequency Generation Unit or FGU (10), a light-emitting diode or LED (20), a sensor element (30), a phase shifter (40), a photo detector (50), a radio frequency (RF) switch (60), a low pass filter (LPF) (70), a trans-impedance amplifier (TIA) (80), and a digital processor (not shown). The photo detector (50) is configured to convert a fluorescence signal from the sensor element (30) into an electrical current signal and also, to multiply the fluorescence signal with either the quadrature signal or the known in-phase signal as selected by the RF switch (60).
Description
A SYSTEM AND METHOD TO EXTRACT PHASE SHIFT OF A FLUORESCENCE
SIGNAL
FIELD OF INVENTION
The present invention relates to a system and method to extract phase shift of fluorescence signal.
BACKGROUND OF THE INVENTION
Fluorescence is the emission of light by a substance such as molecule, after it has absorbed light or other electromagnetic radiation. The substance absorbs light at a particular wavelength and subsequently emits light with a longer wavelength. However, there is a slight time delay in between the absorption and the emission of light. The delay is also known as the fluorescence lifetime. Analysis of the fluorescence from a sample can be done through fluorescence spectroscopy or also known as fluorometry. Through the analysis, information such as the spectrum and the lifetime of the fluorescence can be obtained. There is a number of different fluorometry techniques exist, which include the intensity-based techniques and fluorescence lifetime techniques. These different techniques serve to the same purpose of extracting information of fluorescence signal.
Many researches have been done to produce systems and methods that can extract information of fluorescence signal. An example of such system is disclosed in a United States Patent Publication No. 5981957, wherein the system extracts information of the fluorescence signal such as the fluorescence lifetime and fluorescence spectrum through chemometric analysis. This is done by analysing the differences in the amplitude and phases between the reference signal and data signal. The analysis is done by a digital processor. The reference signal is generated from the mixing of a driving signal and a mixing signal, both produced by two different signal generators. Meanwhile, the data signal is the product from the mixing process of the driving signal and a fluorescence signal. The disclosed system comprises a plurality of signal generators, mixers, filters and analog-to-digital converters.
In another United States Patent Publication No. 5818582, it discloses a system and method to determine the phase of a fluorescence signal. The system
processes a demodulated sample signal which is a combination of a carrier signal and a fluorescence signal along with a reference signal in order to determine the phase and relative depth of the modulation. There are many systems that enable the extraction of information from the fluorescence signal. However, the systems require a plurality of mixers and filters as their key elements. Thus, it is not cost effective and also requires more space. Furthermore, error also needs to be accounted due to part variation in the mixers and filters. Therefore, there is a need to have a system that extracts information of fluorescence signal efficiently and deals with the above mentioned constraints.
SUMMARY OF INVENTION
The present invention provides a system (100) for extracting phase shift of a fluorescence signal. The system (100) comprises a Frequency Generating Unit (10) to generate a known in-phase signal; a light emitting diode (20) to emit modulated visible light; a sensor element (30); a phase shifter (40) to produce a known quadrature signal based on the known in-phase signal; a photo detector (50) to convert a fluorescence signal from the sensor element (30) into an electrical current signal; a radio frequency (RF) switch (60) to select either the known in-phase signal or the known quadrature signal at one time; a low pass filter (70) to remove high frequency element in a signal; a trans-impedance amplifier (80) to convert from electrical current signal to electrical voltage signal; and a digital processor configured to extract a phase shift information of the fluorescence signal from an output voltage signal of the trans-impedance amplifier (80). Moreover, the photo detector (50) is further configured to multiply the fluorescence signal with either the quadrature signal or the known in-phase signal.
Preferably, the digital processor extracts phase shift information, φ, of the fluorescence signal by computing an equation below:
0 = ίαη"1 ^-¾ , wherein Vq (t) is the quadrature-phase voltage signal, and V, (t) is the in-phase voltage signal.
The present invention also provides a method to extract phase shift of a fluorescence signal. The method is characterised by the steps of generating a known in-phase signal, X,(t), for modulating a visible light signal; producing a quadrature signal, Xq(t) based on the known in-phase signal, Xj(t); multiplying a fluorescence signal, Y(t), with the known in-phase signal, X(t), by a photo detector (50); removing high frequency products in the multiplied signal of Y(t) and X(t); converting the multiplied signal from current to an in-phase voltage signal, V,(t); multiplying the fluorescence signal, Y(t), with a quadrature signal, Xq(t), by a photo detector (50); removing high frequency products in the multiplied signal of Y(t) and Xq(t); converting the multiplied signal from current to a quadrature-phase voltage signal, Vq(t); and extracting a phase shift information based on the in-phase voltage signal, V,(t) and the quadrature-phase voltage signal, Vq(t), value of V, (t) and Vq (t).
Preferably, the quadrature signal is generated by phase shifting the known in- phase signal, X(t), at 90°.
Preferably, the in-phase voltage signal, V,(t), and the quadrature-phase voltage signal, Vq(t), are stored in a digital processor. Preferably, the phase shift information, φ, of the fluorescence signal is extracted by using an equation below:
wherein Vq (t) is the quadrature-phase voltage signal, and V, (t) is the in-phase voltage signal.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.
FIG. 1 illustrates a system (100) to extract phase shift of a fluorescence signal according to an embodiment of the present invention.
FIG. 2 illustrates a flow chart of a method to extract phase shift of a fluorescence signal according to an embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
A preferred embodiment of the present invention will be described herein below with reference to the accompanying drawings. In the following description, well known functions or constructions are not described in detail since they would obscure the description with unnecessary detail. Reference is made initially to FIG. 1, which illustrates a system (100) to extract phase shift of a fluorescence signal. The system (100) comprises of a Frequency Generation Unit or FGU (10), a light-emitting diode or LED (20), a sensor element (30), a phase shifter (40), a photo detector (50), a radio frequency (RF) switch (60), a low pass filter or LPF (70), a trans-impedance amplifier or TIA (80), and a digital processor (not shown).
The FGU (10) is configured to generate a known in-phase signal, X,(t). The Xi(t) is applied and provide a modulating signal to the LED (20) which emits a modulated visible light. This modulated signal is also called X,(t). X(t) is used to excite the sensor element (30) which resulted in the emission of signal Y(t). Y(t) is the fluorescence signal which contains a phase shift information, φ, denoting the amount of specimen present in a medium as being sensed by the sensor element (30). As an example, the phase information, φ, denotes the concentration level of dissolved oxygen and dissolved ammonia in a medium. The same X(t) signal from the FGU (10) is applied to the phase shifter (40) and the RF switch (60). The FGU (10) is connected to the LED (20), the phase shifter (40), and the RF switch (60).
The phase shifter (40) is used to produce a quadrature signal, Xq(t) based on the known in-phase signal, X,(t). Meanwhile, the RF switch (60) selects and passes either X(t) or Xq(t), at one time.
The photo detector (50) converts the fluorescence signal, Y(t) to electrical current signal and thereon, the photo detector (50) mixes the electrical current, Y(t) with either the in-phase signal, X(t) or the quadrature signal, Xq(t). The resulted mixed
signal of X(t) and Y(t) or Xq(t) and Y(t) is then routed through the LPF (70). Thus, the photo detector (50) is connected to the RF switch (60) and the LPF (70).
The LPF (70) is configured to remove high order mixing products. The output signal of the LPF (70) is then routed to the TIA (80), which converts the output signal in electrical current signal to electrical voltage signal.
The digital processor is configured to extract the phase shift of the fluorescence signal, φ, from the output voltage signal from the TIA (80). The digital processor is connected to the TIA (80).
Referring now to FIG. 2, it illustrates a flow chart of a method to extract phase shift of fluorescence signal according to an embodiment of the present invention. Initially, the FGU (10) generates the known in-phase signal, X,(t), and supplies the known in-phase signal, X,(t), to the LED (20) as in step 200. The known in-phase signal is defined as Xj(t) = /4 sin <yt, wherein A refers to amplitude of the in-phase signal, ω refers to angular frequency of the in-phase signal, and t refers to time. Besides the LED (20), the in-phase signal is also supplied to the phase shifter (40) and the RF switch (60). The phase shifter (40) produces a quadrature signal, Xq(t) based on the known in-phase signal, X,(t), wherein Xq(t) is the known in-phase signal, X(t) with its phase being adjusted 90° by the phase shifter (40). Thus, the quadrature signal is defined as Xq(t) = A cos wt, wherein A refers to amplitude of the quadrature signal, ω refers to angular frequency of the quadrature signal, and t refers to time. Thereon, the RF switch (60) is configured to allow the known in-phase signal,
Xj(t), to pass through the RF switch (60) and thus, enabling the path of the known in- phase signal, X,(t), as in step 300. The known in-phase signal, X,(t), is then multiplied with the fluorescence signal, Y(t), wherein the multiplication process is performed in the photo detector (50). The fluorescence signal, Y(t), is the in-phase signal, X(t), with a phase shift information, φ, that is resulted from the sensor element (30) respond to the oxygen concentration in the medium. The fluorescence signal can be defined as Y(t) = B sin(<yt + φ) + n(t), wherein B refers to amplitude of the fluorescence signal, ω refers to angular frequency of the fluorescence signal, t refers to time, and n(t) refers to noise. The result of the multiplication is then routed through the LPF (70) to remove the high order mixing products.
In step 400, the multiplied signal is further converted by the TIA (80) from current to in-phase voltage signal, Vj(t). Thereon, the in-phase voltage signal, V,(t), is stored in a digital processor.
Next, the RF switch (40) is configured to enable the path of the known quadrature signal, Xq(t) as in step 500. The quadrature signal, Xq(t), is then multiplied with the fluorescence signal, Y(t), wherein the multiplication process is performed in the photo detector (50). The result of the multiplication is then routed through the LPF (70) to remove the high order mixing products in the multiplied signal. The multiplied signal is further converted by the TIA (80) from current to quadrature-phase voltage signal, Vq(t), and thereon, the quadrature-phase voltage signal, Vq(t), is stored in a digital processor, as in step 600.
In step 700, the digital processor extracts the phase shift information, φ, of the fluorescence signal by using the equati
wherein Vq (t) is the quadrature-phase voltage signal, and V, (t) is the in-phase voltage signal. The phase shift information, φ, denotes the amount of specimen present in a medium as being sensed by the sensor element (30) such as the concentration level of dissolved oxygen or dissolved ammonia.
While embodiments of the invention have been illustrated and described, it is not intended that these embodiments illustrate and describe all possible forms of the invention. Rather, the words used in the specifications are words of description rather than limitation and various changes may be made without departing from the scope of the invention.
Claims
A system (100) for extracting phase shift of a fluorescence signal comprising: a) a Frequency Generating Unit (10) to generate a known in-phase signal,
b) a light emitting diode (20) to emit modulated visible light,
c) a sensor element (30),
d) a phase shifter (40) to produce a known quadrature signal based on the known in-phase signal,
e) a photo detector (50) to convert a fluorescence signal from the sensor element (30) into an electrical current signal, and
f) a low pass filter (70) to remove high frequency element in a signal, characterised in that:
g) the photo detector (50) is further configured to multiply the fluorescence signal with either the quadrature signal or the known in- phase signal; and
h) the system (100) further includes:
i. a radio frequency (RF) switch (60) to select either the known in- phase signal or the known quadrature signal at one time, ii. a trans-impedance amplifier (80) to convert from electrical current signal to electrical voltage signal, and
iii. a digital processor configured to extract a phase shift information of the fluorescence signal from an output voltage signal of the trans-impedance amplifier (80).
The system (100) as claimed in claim 1 , wherein the digital processor extracts phase shift information, φ, of the fluorescence signal by computing an equation below:
wherein Vq (t) is the quadrature-phase voltage signal, and V, (t) is the in-phase voltage signal.
3. A method to extract phase shift of a fluorescence signal is characterised by the steps of:
a) generating a known in-phase signal, X,(t), for modulating a visible light signal;
b) producing a quadrature signal, Xq(t) based on the known in-phase signal, Xj(t);
c) multiplying a fluorescence signal, Y(t), with the known in-phase signal, X,(t), by a photo detector (50);
d) removing high frequency products in the multiplied signal of Y(t)
e) converting the multiplied signal from current to an in-phase voltage signal, Vj(t);
f) multiplying the fluorescence signal, Y(t), with a quadrature signal, Xq(t), by a photo detector (50);
g) removing high frequency products in the multiplied signal of Y(t) and Xq(t);
h) converting the multiplied signal from current to a quadrature-phase voltage signal, Vq(t); and
i) extracting a phase shift information based on the in-phase voltage signal, V,(t) and the quadrature-phase voltage signal, Vq(t), value of
The method as claimed in claim 3, wherein the quadrature signal is generated by phase shifting the known in-phase signal, X,(t), at 90°.
The method as claimed in claim 3, wherein the in-phase voltage signal, V,(t), and the quadrature-phase voltage signal, Vq(t), are stored in a digital processor.
The method as claimed in claim 3, wherein the phase shift information, φ, of the fluorescence signal is extracted by using an equation below:
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MYPI2014703006 | 2014-10-13 | ||
| MYPI2014703006A MY181662A (en) | 2014-10-13 | 2014-10-13 | A system and method to extract phase shift of a fluorescence signal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2016060543A1 true WO2016060543A1 (en) | 2016-04-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/MY2015/050059 Ceased WO2016060543A1 (en) | 2014-10-13 | 2015-06-19 | A system and method to extract phase shift of a fluorescence signal |
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| MY (1) | MY181662A (en) |
| WO (1) | WO2016060543A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112697762A (en) * | 2021-01-07 | 2021-04-23 | 中山复旦联合创新中心 | High-precision dissolved oxygen meter system and special SoC |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010014505A1 (en) * | 2008-07-28 | 2010-02-04 | Sensors For Medicine & Science, Inc. | Systems and methods for optical measurement of analyte concentration |
| US20110168917A1 (en) * | 2008-09-19 | 2011-07-14 | Mitsui Engineering & Shipbuilding Co., Ltd. | Fluorescence detection device using intensity-modulated laser light and fluorescence detection method |
| US20120025098A1 (en) * | 2009-02-13 | 2012-02-02 | Mitsui Engineering & Shipbuilding Co., Ltd. | Fluorescence detection device and fluorescence detection method |
| JP2013190221A (en) * | 2012-03-12 | 2013-09-26 | Mitsui Eng & Shipbuild Co Ltd | Fluorescence detector and fluorescence detection method |
-
2014
- 2014-10-13 MY MYPI2014703006A patent/MY181662A/en unknown
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- 2015-06-19 WO PCT/MY2015/050059 patent/WO2016060543A1/en not_active Ceased
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010014505A1 (en) * | 2008-07-28 | 2010-02-04 | Sensors For Medicine & Science, Inc. | Systems and methods for optical measurement of analyte concentration |
| US20110168917A1 (en) * | 2008-09-19 | 2011-07-14 | Mitsui Engineering & Shipbuilding Co., Ltd. | Fluorescence detection device using intensity-modulated laser light and fluorescence detection method |
| US20120025098A1 (en) * | 2009-02-13 | 2012-02-02 | Mitsui Engineering & Shipbuilding Co., Ltd. | Fluorescence detection device and fluorescence detection method |
| JP2013190221A (en) * | 2012-03-12 | 2013-09-26 | Mitsui Eng & Shipbuild Co Ltd | Fluorescence detector and fluorescence detection method |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112697762A (en) * | 2021-01-07 | 2021-04-23 | 中山复旦联合创新中心 | High-precision dissolved oxygen meter system and special SoC |
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| Publication number | Publication date |
|---|---|
| MY181662A (en) | 2020-12-31 |
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