Classifications

• • 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
  • G01N21/645—Specially adapted constructive features of fluorimeters
• • 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
  • G01N21/84—Systems specially adapted for particular applications
  • G01N21/85—Investigating moving fluids or granular solids
  • G01N21/8507—Probe photometers, i.e. with optical measuring part dipped into fluid sample
• • 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
  • G01N21/645—Specially adapted constructive features of fluorimeters
  • G01N2021/6463—Optics

Definitions

• the present disclosure generally relates to the field of optica! sensor probes for collection of luminescence generated at a dielectric interface, and more particularly, an optical sensor probe employing a parabolic optical waveguide optimized for the efficient collection of luminescence generated at a dielectric interface.
• Luminescence-based optical sensors detect anaiyte-induced changes in a luminescence signal. Such changes may be brought about due to the anaiyte-induced quenching of luminescence from an analyte-sensitive luminescent compound, which is the case for a broad range of optical chemical sensors including sensors for oxygen, carbon dioxide, pli and chloride.
• the luminescent compound is typically encapsulated within a porous, solid matrix that can be deposited onto a substrate as a thin film.
• luminescence-based optical sensors may be based on the binding of the analyte of interest to a surface using suitable receptor molecules. Luminescence is imparted to such a system through the use of a luminescent label that can be attached to the anaiyte itself or to an additional molecule that binds to the surface-bound anaiyte. Changes in the level of luminescence are indicative of changes in the concentration of anaiyte that is bound to the surface. This methodology is commonly employed for the development of luminescence- based optica! biosensors.
• the measurement task is to detect selectively luminescence from molecules bound close to the surface, excluding any signal from unbound molecules in the environment above the surface. This detection principle is also relevant to thin film-based optical chemical sensors.
• the sensor probe should incorporate an apparatus that allows for the efficient collection of surface-generated luminescence and the detection principle can be intensity-based or lifetime-based depending on the desired application.
• the probe should also be modular in nature, facilitating the detection of a variety of anaiytes using the correct combination of sensing material and optical / optoelectronic components.
• an optical probe for detecting luminescence emitted by a sample includes a parabolic optical waveguide and an outer housing configured to hold the optical waveguide having a detachable component.
• the optical probe also includes a sensing material for detection of at least one anaJytc, An excitation source is configured to excite the sensing material and a measuring photodet ⁇ ctor detects emitted luminescence,
• the optical probe further includes a waveguide mount between the outer housing and the detachable component configured to hold the waveguide in place, collection optics to focus emitted light onto the photodetector and an emission filter configured to allow emitted light to pass.
• the optical probe includes a transparent sensor substrate, such as. for example, a cover slip or microscope slide, between the detachable component and the waveguide.
• the sensing material may be deposited on the transparent sensor substrate. In art alternative embodiment, the sensing material may he deposited directly on the waveguide.
• the optical probe includes an airway adapter attached to the optical probe.
• the airway adapter allows for the detection of a user's breath.
• the optical probe may be used to detect -various anaiytes including, but not limited to, oxygen, carbon dioxide, pH, phosphate, nitrate, ammonia, chloride, other chemical species or a range of biomolec ⁇ les such as DNA. enzymes or antibodies.
• the optical probe Includes a reference photodiode configured to measure backscatter from said excitation source.
• at least one sealing ⁇ ng may be incorporated to provide connection between the outer housing, the waveguide mount, the waveguide, and the detachable component.
• the optical probe includes a measuring photomultiplier tube.
• FiG. 1 is a plan cross-sectional view of one embodiment of an optical sensor probe, in accordance with the principles of the present disclosure
• FIG. 2 is a plan cross-sectional view of another embodiment of an optical sensor probe, in accordance with the principles of the present disclosure
• FlG. 3 is a schematic view of one use of the optical sensor probe shown in FIG, 1 ;
• FlG. 4 is a chart showing the response of the optical sensor probe of FIG. I as a function of dissolved oxygen concentration;
• FIG. 5 is a chart showing a corresponding calibration curve of FIG. 4;
• n a chart showing real-time detection of DNA hybridization:
• FKl. 7 is a schematic view of the use of the optical sensor probe according to the present disclosure incorporated in a breath monitoring device; and FIG. 8 is a chart showing real time detection of oxygen during breath monitoring
• the various exemplary embodiments of the present invention arc directed to optical sensor probes that include a parabolic optical waveguide, optimized for the efficient collection of fluorescence generated at a dielectric interface.
• An optimized optical configuration and probe of the current disclosure is shown in Figure 1 and incorporates a waveguide with low cost components arranged in a probe geometry.
• Figure 1 shows an optical sensor probe configuration that may be used for gas and/or chemical sensing applications. Additionally, the optical sensor probe configuration may be used in bios ⁇ nsing applications, The apparatus may be used for luminescence intensity-based or lifetime-based measurements. The dimensions shown are merely indicative of the scale ⁇ f the device itself. The size of the probe can be tailored to suit specific applications.
• an optical sensor probe 10 includes an outer housing 12 with a detachable cap 14, between which is a waveguide mount 16 fixing in place a parabolic optical waveguide 18.
• the detachable cap may be any removable or replaceable component that assists in placement and application of a sensing material.
• the connections between the outer housing 12 and wa ⁇ eguidc mount 16, and the detachable cap 14 and waveguide mount 16 are optional sealing rings 20, which may be employed if required by the application.
• Between the cap 14 and the waveguide 18 is a transparent sensor substrate 22 upon which the sensing material may be deposited.
• the transparent sensor substrate 22 may be, for example, a cover slip or a microscope slide.
• an immersion oil may be used to ensure good optical transmission between the waveguide 18 and the transparent sensor substrate 22,
• the sensing material may be deposited directly onto the waveguide 18.
• the detachable cap 14 is used to house the transparent sensor substrate 22 onto which the sensing material is deposited.
• the sensor substrate is attached to the cap by means of an adhesive and the cap is threaded for ease of connection to the waveguide mount 16. If it is desired to change the sensing functionality of the probe, this can be achieved by attaching a sensor cap that houses a sensor substrate onto which a different sensing material has been deposited.
• the sensing cap couid have an integrated sensing region that replaces the sensor substrate, making the cap itself a disposable sensing element.
• the parabolic optical waveguide may be constructed of plastic or glass. However, other materials and media may be used including a liquid medium surrounding the waveguide or other solid bodies such as a plastic/glass interface.
• the sensing material is excited using an excitation source 24.
• the excitation source 24 may be, for example, an excitation LED such that fluorescent light is emitted when the excitation LED excites the sensing material.
• the light from the excitation source 24 passes through an aperture 26 and an excitation filter 28 before being focused by a lens 30 on the sensing material.
• the excitation filter 28 removes from the excitation light any spectra! components that may coincide with the transmission region of the emission filter 34, components that would otherwise lead to an undesirably high background signal.
• a reference photodiode 32 may be used to measure backscatter from the excitation source, thereby providing compensation for fluctuations in the emission of the source.
• the sensing material will emit luminescence in the presence of the molecule of interest.
• the sensing materia ⁇ should be selected so that its absorption wavelength coincides with the emission wavelength of the light source, for example, ruthenium or porphyrin complexes, Rhodamine or a Cyanin dye such as Cy 5 may be suitable fluorescent dyes.
• the parabolic optica! waveguide 18 is configured such that luminescence emitted from the sensing material is directed towards the detection set up. As will be discussed in further detail below, Figure 2 shows the emitted ray path. Referring back to Figure 1, the emitted light passes through an emission filter 34 and collection optics 36 before being detected by a measuring photodetector 38.
• the measuring photodetector 38 may be, for example, an avalanche photodiode suitable for counting single photons, a silicon PlN photodiode, a photomuHiper, or a CCD chip. Also shown is wiring 40 which is used to control the various elements described herein. The signal output from the measuring photodetector 38 is acquired and processed using appropriate software.
• excitation filter Semrock, FF01-447-60
• emission filter Semroek, FFOl -583- 120
• focusing lens Edmund Optics, 6mm half-ball, NT45-935
• ph ⁇ todiodes Hamamatsu, S 1223-01 , Si
• FIG. 2 shows an optical probe 50 that is configured for biosensing applications and is tailored for the detection of Cy5, Cyanin fluorescence.
• the optical probe 50 of Figure 2 Includes an outer housing 52 with a detachable cap 54, between which is a waveguide mount 56 fixing in place a waveguide 58.
• the connections between the outer housing 52 and waveguide mount 56, and the detachable cap 54 and waveguide mount 56 are optional sealing rings 60.
• a transparent sensor substrate 62 is between the cap 54 and the waveguide 58. Sensing material may be deposited on the transparent sensor substrate 62 or may also be deposited directly onto the waveguide 58.
• the sensing material is excited using an excitation source 64,
• the light from the excitation source 64 passes through an aperture 66 and an excitation filter 68 before being focused by a lens 70 on the sensing material.
• a reference photodiode 72 may be used to measure back&catter from the excitation source.
• the emitted light from the sensing material passes through an emission filter 74 and collection optics 76 before being detected by a measuring phoiomultiplier tube (PMT) 78.
• PMT measuring phoiomultiplier tube
• a super critical angle fluorescence aperture (SAF aperture) to block signals that are not generated by surface- specific binding.
• the adapter 80 acts a physical interface between the optical probe and the
• the optical probe as shown in Figures 1 and 2 may be used for the detection of a variety of analytes and/or parameters.
• a broad range of gases or chemicals may be detected, given a suitable, fluorescence-based sensing chemistry.
• gases or chemicals For example, oxygen, carbon dioxide, pFL phosphate, nitrate, chloride, ammonia or other chemicals of interest can be detected.
• the probe may also be used as an optical biosensor for the detection of biomolecules such as, but not limited to, DNA, enzymes or antibodies.
• an optical probe 90 was integrated into a durable polymer housing and subsequently applied to the detection of dissolved oxygen (DO) as a proof of principle, employing phase fhiorometric detection as shown in Figure 3.
• DO dissolved oxygen
• the sensing material was a known sol-gel thin film based on a n ⁇ propyltriethoxysilane (PTEOS) precursor containing the fluorescent ruthenium complex [Ru(II)-tris(4J-diphenyl-lJ 0-phenanthroline)] ( Ru(dpp) 3 2 ⁇ ).
• the film preparation may include 1 mole PTEOS / 4 H2O / 6.25 EtOH / 7.2x10-3 HCl with a molar ratio dye [Ru(UPP) 3 -"] / PTEOS - 1.4x10-3; dissolve [Ru(dpp) 3 2 l in EtOH and stir until complex dissolves; add PTEOS while stirring; and add HC! (pH 1 ) slowly, dropwise while stirring.
• the solution may be left stirring for at least 3 weeks before use.
• the probe response as a function of dissolved oxygen (DO) concentration is shown in Figure 4 with the corresponding calibration curve shown in Figure 5.
• the limit of detection (LOD) for DO was determined to be less than 1.5 ppb 5 with an integration time of 0.6 seconds.
• the LOD compares favorably to an electrochemical dissolved oxygen sensor available commercially from YSl (e.g., YSI product - product name YSI 550A Dissolved Oxygen Meter - Minimum resolution 0.01mg/L or lOppb).
• FIG. 6 8 graph representing real-time detection of DNA hybridization is shown in Figure 6.
• Figure 6 shows two curves that were recorded by a photon-counting photomultiplier tube (PMT) to which the probe was attached, as shown in Figure 2.
• the luminescence signal increases significantly for one curve and remains relatively unchanged for the other.
• the former represents the response of the sensor to a 20- mer match sample of single stranded DNA, which was labeled with the fluorescent indicator. CyS.
• Each data point corresponds to the number of photons recorded by the PMT over a period of 500ms.
• the marked increase in signal upon introduction of the 20-mer match sample is indicative of binding of the sample DNA to the receptor DNA on the surface of the sensor sample.
• a hand-held device for breath gas analysis 110 is shown in Figure 7.
• An airway adapter 114 is connected to the optical probe 112.
• the airway adapter replaces the detachable sensor cap 14 shown in Figure 3.
• the probe 120 may be surrounded by housing 122.
• the airway adapter 1 14 allows a user's breath to interact with the sensing element 118 of the optical sensing probe 120
• the hand-held device 110 may be configured to be connected to a power source, a PC, a PDA or other device to assist in the gathering and processing of information. It is also contemplated that the probe according to the present disclosure may be incorporated into a mask to monitor a user's breath. The device may also be wireless to provide ease of mobility for the user.
• Figure 8 shows real-time detection of oxygen in human breath. The data were recorded by having a test subject breathe into the airway adapter 114 while at rest, which corresponds to a breath rate of approximately 10 breaths per minute.
• FIG. 8 shows the real-time evolution of the in-brea ⁇ h oxygen concentration as recorded by the sensor.
• the system is compatible with the detection of a broad range of analytes in breath, including carbon dioxide, ammonia and anaesthetic gases, given a suitable sensing material.

Landscapes

• Health & Medical Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Biochemistry (AREA)
• Physics & Mathematics (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
• Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Priority Applications (3)

Applications Claiming Priority (2)

Publications (2)

Family

ID=39157642

Family Applications (1)

Country Status (5)

Cited By (3)

Families Citing this family (10)

Citations (3)

Family Cites Families (6)

• 2007
  • 2007-05-07 US US12/299,666 patent/US8163241B2/en not_active Expired - Fee Related
  • 2007-05-07 CN CNA2007800162767A patent/CN101438145A/zh active Pending
  • 2007-05-07 WO PCT/IB2007/003920 patent/WO2008029298A2/en not_active Ceased
  • 2007-05-07 EP EP07849024A patent/EP2016393A2/en not_active Withdrawn
  • 2007-05-07 JP JP2009508548A patent/JP2009536339A/ja active Pending

Patent Citations (3)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events