WO1990001697A1 - Blood glucose monitoring - Google Patents
Blood glucose monitoring Download PDFInfo
- Publication number
- WO1990001697A1 WO1990001697A1 PCT/GB1989/000899 GB8900899W WO9001697A1 WO 1990001697 A1 WO1990001697 A1 WO 1990001697A1 GB 8900899 W GB8900899 W GB 8900899W WO 9001697 A1 WO9001697 A1 WO 9001697A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- waveguide
- light
- blood
- optical waveguide
- light source
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/1459—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters invasive, e.g. introduced into the body by a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
- A61B5/6846—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
- A61B5/6847—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
- A61B5/6848—Needles
-
- 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
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/41—Refractivity; Phase-affecting properties, e.g. optical path length
- G01N21/43—Refractivity; Phase-affecting properties, e.g. optical path length by measuring critical angle
- G01N21/431—Dip refractometers, e.g. using optical fibres
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
Definitions
- Optical fibres generally have a central core, entirely surrounded by a plastics or glass sheath (the cladding) .
- the refractive index of the core In order for optical transmission along such a fibre to take place, the refractive index of the core must be greater than that of the cladding. It is well known that the relative index of refraction of the core and cladding will determine the transmission characteristics of light along the optical fibre.
Abstract
Apparatus for blood glucose monitoring, which comprises: (a) a total internal reflection waveguide having a core and reflective cladding, at least part of the core being devoid of such cladding; (b) a light source (such as a laser) optically coupled to an end of the waveguide; (c) a light detector arranged to generate a signal representing the quantity of light transmitted from the light source through the waveguide past the unclad part; and (d) an insulin administration device which is such that insulin is administered to a patient when the quantity of light detected by the detector changes by more than a predetermined amount.
Description
Blood Glucose Monitoring
The present invention is concerned with an apparatus and method for monitoring blood glucose, in which the refractive index of the blood is monitored or measured.
It is known to measure and indicate or record the refractive index of various liquids by detecting the attenuation of internally reflected light passing through a transparent optical waveguide, such as a glass rod, an optical fibre or the like.
Optical fibres generally have a central core, entirely surrounded by a plastics or glass sheath (the cladding) . In order for optical transmission along such a fibre to take place, the refractive index of the core must be greater than that of the cladding. It is well known that the relative index of refraction of the core and cladding will determine the transmission characteristics of light along the optical fibre.
According to Snell's law, n2 sin x nl sin y, in which nl is the refractive index of the cladding, n2 -S the refractive index of the core, x is the angle of incidence at the core/cladding interface and y is the angle at which an optical beam transmitted along the core escapes therefrom. If \ and n remain constant, then there is an angle x at which y will equal 90 degrees; this angle (called the critical angle) is the minimum angle at which total internal reflection takes place.
If a ray of light strikes the core/cladding interface at an angle greater than the critical angle, then the ray will be internally reflected within the core at a reflected angle equal to the angle of incidence; if the angle of incidence is less than the critical angle, then losses will occur. The critical angle (Xcr) is derived from Snell's law as Xcr = arc sin (n^/r^) .
If part of the cladding is removed, then the degree of attenuation of a light beam transmitted along the optical fibre will depend on the refractive index of the medium in which the bared portion of optical fibre or other waveguide is disposed. This phenomenon has been proposed as the basis for measurement of the refractive index of a test liquid in, for example, U.K. patent specifications 2105034 and 1507747.
We have now established that this type of technique is particularly suitable for producing a measure of glucose concentration in blood, because variation in the glucose concentration causes detectable variation in the refractive index.
The blood glucose concentration of a healthy person is generally about 1% (by weight) , although a variation of plus or minus 0.37= is acceptable. In a diabetic patient, the blood glucose concentration can vary widely, which can result in serious complications, such as cardiovascular problems and eye disorders. We have established that a 0.1% change in glucose concentration can result in a change of the optical transmission of greater than 1%, which is a substantial and detectable change.
A blood glucose monitor which measures the glucose level of blood using a refractometer is known from U.S. Patent 4704029. In the blood glucose monitor disclosed in the latter document, a prism is used to form an optical interface with the blood being monitored.
Ve have found that the use of such a prism requires a bulky insert into the body of the patient; furthermore, a rigid support is required for the prism to prevent movement which could otherwise cause irregularities in the detected refractive index. It is an object of the present invention to provide blood glucose monitoring apparatus in which the above disadvantages are at least alleviated.
According to the present invention, therefore, there is provided apparatus for monitoring the glucose level of blood which comprises an elongate optical waveguide capable of transmitting light by internal reflection, said waveguide comprising a core and a reflective cladding, at least part of the core being devoid of said cladding, said part being such that it can be positioned in direct contact with the blood to be monitored; a light source (such as a laser) optically coupled to an end of the optical waveguide; light detection means arranged to generate a signal representative of the quantity of light transmitted from the light source through the waveguide via said part; and means for initiating insulin administration when the quantity of light detected by said light detection means changes by more than a predetermined amount.
The present invention further comprises a method of determining the glucose content of blood, which comprises transmitting a light beam along an optical waveguide, in which at least one portion of the waveguide is devoid of reflective cladding and is in contact with the blood; and monitoring the attenuation of transmitted light passing said unclad portion. The output from the optical waveguide is preferably used to provide positive feedback control of administration of insulin to a patient. The method according to the invention is preferably carried out using apparatus according to the inventio .
The light detection means may, in one embodiment of the invention, be coupled to an output end of the waveguide remote from the light source end. However, this may necessitate the location of processing electronics at the output end; according to another embodiment of the invention, therefore, the waveguide may be provided with a reflective end remote from the light source. In this case, the light detection means is coupled to an output end of the waveguide remote from the reflective end.
In a preferred embodiment of the invention, a further optical waveguide is provided in thermal contact with the first-mentioned optical waveguide along substantially the entire length of the unclad portion. This further optical waveguide is preferably clad along substantially its entire length, such that there is substantially minimal optical attenuation along the length thereof. This further optical waveguide thus provides compensation for extraneous changes in refractive index (such as those caused by temperature changes) .
The optical waveguide used in the method and apparatus according to the invention may be a conventional optical fibre; optical fibres generally have a good quality, consistent circular cross-section. According to a preferred embodiment of the invention, however, the optical waveguide preferably comprises an elongate body with a polygonal (e.g. rectangular) cross-section, preferably with geometrically parallel faces along the length of the waveguide. The use of a waveguide with such parallel faces substantially minimises distortion and loss of clarity of the transmitted optical beam. The flat surfaces of the rectangular cross-section may advantageously be polished to optical quality.
The invention will be further described, by way of example only, -with reference to the accompanying drawings, in which:
Figure 1 is a schematic illustration of glucose monitoring apparatus according to the invention; and
Figure 2 is a sectional view of apparatus for injecting a waveguide into a patient's bloodstream, for use in apparatus according to the invention.
Referring to Figure 1 there is shown a blood flow 1 in the direction of arrow A along tubular member 11 (which may be a blood vessel or an extracorporeal conduit); an optical waveguide 2, an unclad portion of which is diposed in the blood flow. Part of the output from a laser source 3 is passed to a reference photodiode 4 and the remainder of the output to a signal photodiode 5. The outputs from both reference photodiode 4 and signal photodiode 5 are passed to electronic signal processor 6. The output from the processor is then input to an analogue-to-digital convertor 7, the digital output of which is input to a process controller 8 (e.g. a single chip microprocessor) . The process controller is operatively connected to an insulin pump 9, arranged for administration of insulin 10 to the blood flow 1.
The processed signal from photodiode 5 is compared by signal processor 6 with that from reference photodiode 4, so as to give a measure of the attenuation of light through the waveguide 2. The resultant measure of attenuation of light can, when the system is appropriately calibrated, give a measure of the refractive index of the blood and therefore the glucose content thereof; the signal processor 6 is used to generate a signal which is itself arranged to trigger operation of the insulin pump 9 and thence administration of insulin into the blood.
In a preferred embodiment of the invention, the part of the output from the laser source 3 which is passed to reference photodiode 4 may pass in parallel to the light passed
through the waveguide 2 through a further waveguide (not shown) which is in thermal contact with waveguide 2 preferably along the entire length thereof.
Referring to Figure 2, there is shown a hollow jacket 12 having a sharp pointed end 13 to be inserted into a patient by means of a hypodermic injection device (not shown) . Located within the jacket is the free end portion of a waveguide 14 having a reflective end 15 and a portion 16 with the cladding removed.
In use, the pointed end 13 of jacket 12 is inserted into a blood vessel of a patient; the jacket is then removed leaving the waveguide in place. A light source and detector electronics are then coupled to the external end of the waveguide, which can then be used to control the administration of insulin to the patient.
Claims
1. Apparatus for monitoring the glucose content of blood, which comprises an elongate optical waveguide capable of transmitting light by internal reflection, said waveguide comprising a core and a reflective cladding, at least part of the core being devoid of said cladding, said part being such that it can be positioned in direct, contact with the blood to be monitored; a light source optically coupled to an end of the optical waveguide; light detection means arranged to generate a signal representative of the quantity of light transmitted from the light source through the waveguide via said part; and means for initiating insulin administration to said blood when the quantity of light detected by the detector changes by more than a predetermined amount.
2. Apparatus according to claim 1, wherein said light source is a laser.
3. Apparatus according to claim 1 or 2 , which further comprises means for insertion of at least the unclad portion of said waveguide into the bloodstream of a patient .
4. Apparatus according to claim 3, wherein said insertion means comprises a sharp metal housing arranged to be secured to a hypodermic syringe or the like, said housing substantially encompassing said unclad portion.
5. Apparatus according to any of claims 1 to 4, wherein said light detection means is coupled to an output end of said waveguide remote from said light source end.
6. Apparatus according to any of claims 1 to 4, wherein said waveguide is provided with a reflective end remote from said light source end, said light detection means being coupled to an output end of said waveguide remote from said reflective end.
7. Apparatus according to any of claims 1 to 6, wherein a further optical waveguide is provided in thermal contact with said first-mentioned optical waveguide along substantially the entire length of the unclad portion thereof, preferably along substantially the entire length of the first-mentioned waveguide.
8. Apparatus according to any of claims 1 to , wherein said optical waveguide comprises an elongate body having a polygonal cross-section.
9. A method of determining the glucose content of blood, which comprises transmitting a light beam along an optical waveguide, In which at least one portion of the waveguide is devoid of reflective cladding and is in contact with said blood; monitoring the attenuation of transmitted light passing said unclad portion; and, preferably, using the output from the optical waveguide to provide positive feedback control of administration of insulin to a patient.
10. A method according to claim 9, wherein apparatus according to any of claims 1 to 8 is employed.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8818690.3 | 1988-08-05 | ||
GB888818690A GB8818690D0 (en) | 1988-08-05 | 1988-08-05 | Refractive index measurement |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1990001697A1 true WO1990001697A1 (en) | 1990-02-22 |
Family
ID=10641695
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1989/000899 WO1990001697A1 (en) | 1988-08-05 | 1989-08-07 | Blood glucose monitoring |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU4053489A (en) |
GB (1) | GB8818690D0 (en) |
WO (1) | WO1990001697A1 (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE9110757U1 (en) * | 1991-08-30 | 1992-02-13 | Klein, Rainer, 5840 Schwerte, De | |
WO1993009421A1 (en) * | 1991-11-04 | 1993-05-13 | Novo Nordisk A/S | Apparatus for ex vivo measurement of blood sugar levels |
WO1999058048A1 (en) * | 1998-05-13 | 1999-11-18 | Biosensor, Inc. | Apparatus and method for noninvasive glucose measurement |
FR2832505A1 (en) * | 2001-11-16 | 2003-05-23 | Inst Francais Du Petrole | FIBER OPTIC REFRACTOMETER |
US6584335B1 (en) | 1997-08-09 | 2003-06-24 | Roche Diagnostics Gmbh | Analytical device for in vivo analysis in the body of a patient |
DE102004055032A1 (en) * | 2004-11-15 | 2006-08-03 | Roche Diagnostics Gmbh | Optical device for determining glucose concentration in interstitial fluid, useful particularly where measured values are used to regulate insulin release |
WO2006095343A1 (en) | 2005-03-10 | 2006-09-14 | Anatoly Babchenko | An optical sensor and a method of its use |
WO2007090147A2 (en) * | 2006-01-31 | 2007-08-09 | The Board Of Trustees Of The University Of Illinois | Method and apparatus for measurement of optical properties in tissue |
US7586618B2 (en) | 2005-02-28 | 2009-09-08 | The Board Of Trustees Of The University Of Illinois | Distinguishing non-resonant four-wave-mixing noise in coherent stokes and anti-stokes Raman scattering |
US7623908B2 (en) | 2003-01-24 | 2009-11-24 | The Board Of Trustees Of The University Of Illinois | Nonlinear interferometric vibrational imaging |
US8983580B2 (en) | 2008-01-18 | 2015-03-17 | The Board Of Trustees Of The University Of Illinois | Low-coherence interferometry and optical coherence tomography for image-guided surgical treatment of solid tumors |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1040271A (en) * | 1975-01-22 | 1978-10-10 | Anthony M. Albisser | Artificial beta cell |
US4169676A (en) * | 1976-02-20 | 1979-10-02 | Nils Kaiser | Method for determining the contents of metabolic products in the blood |
DE3232059A1 (en) * | 1981-09-04 | 1983-03-24 | Westinghouse Electric Corp., 15222 Pittsburgh, Pa. | GLASS FIBER DETECTOR |
GB2121556A (en) * | 1982-03-31 | 1983-12-21 | Nippon Beet Sugar Mfg | Determining refractive index of a liquid |
US4706677A (en) * | 1985-09-23 | 1987-11-17 | Spectramed, Inc. | Multiple sensor bundle |
WO1988001376A1 (en) * | 1986-08-14 | 1988-02-25 | Radiometer A/S | Method and apparatus for determining the level of an analyte in a sample of whole blood |
-
1988
- 1988-08-05 GB GB888818690A patent/GB8818690D0/en active Pending
-
1989
- 1989-08-07 WO PCT/GB1989/000899 patent/WO1990001697A1/en active Application Filing
- 1989-08-07 AU AU40534/89A patent/AU4053489A/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1040271A (en) * | 1975-01-22 | 1978-10-10 | Anthony M. Albisser | Artificial beta cell |
US4169676A (en) * | 1976-02-20 | 1979-10-02 | Nils Kaiser | Method for determining the contents of metabolic products in the blood |
DE3232059A1 (en) * | 1981-09-04 | 1983-03-24 | Westinghouse Electric Corp., 15222 Pittsburgh, Pa. | GLASS FIBER DETECTOR |
GB2121556A (en) * | 1982-03-31 | 1983-12-21 | Nippon Beet Sugar Mfg | Determining refractive index of a liquid |
US4706677A (en) * | 1985-09-23 | 1987-11-17 | Spectramed, Inc. | Multiple sensor bundle |
WO1988001376A1 (en) * | 1986-08-14 | 1988-02-25 | Radiometer A/S | Method and apparatus for determining the level of an analyte in a sample of whole blood |
Non-Patent Citations (2)
Title |
---|
JAPANESE JOURNAL OF APPLIED PHYSICS, Vol. 22, No. 12, December 1983, TAKASHI TAKEO et al., "Fluid Observation with an Optical Fiber Photorefractometer", page 1920. * |
OPTICS AND LASER TECHNOLOGY, Vol. 17, No. 1, February 1985, I.N. ROSS et al., "Optical Monitoring of Glucose Concentration", pages 31-35. * |
Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE9110757U1 (en) * | 1991-08-30 | 1992-02-13 | Klein, Rainer, 5840 Schwerte, De | |
WO1993009421A1 (en) * | 1991-11-04 | 1993-05-13 | Novo Nordisk A/S | Apparatus for ex vivo measurement of blood sugar levels |
US6584335B1 (en) | 1997-08-09 | 2003-06-24 | Roche Diagnostics Gmbh | Analytical device for in vivo analysis in the body of a patient |
WO1999058048A1 (en) * | 1998-05-13 | 1999-11-18 | Biosensor, Inc. | Apparatus and method for noninvasive glucose measurement |
FR2832505A1 (en) * | 2001-11-16 | 2003-05-23 | Inst Francais Du Petrole | FIBER OPTIC REFRACTOMETER |
US6975388B2 (en) | 2001-11-16 | 2005-12-13 | Institut Francais Du Petrole | Optical-fiber refractometer |
US7623908B2 (en) | 2003-01-24 | 2009-11-24 | The Board Of Trustees Of The University Of Illinois | Nonlinear interferometric vibrational imaging |
DE102004055032B4 (en) * | 2004-11-15 | 2006-12-07 | Roche Diagnostics Gmbh | Apparatus and method for determining the concentration of glucose in interstitial fluid |
DE102004055032A1 (en) * | 2004-11-15 | 2006-08-03 | Roche Diagnostics Gmbh | Optical device for determining glucose concentration in interstitial fluid, useful particularly where measured values are used to regulate insulin release |
US7586618B2 (en) | 2005-02-28 | 2009-09-08 | The Board Of Trustees Of The University Of Illinois | Distinguishing non-resonant four-wave-mixing noise in coherent stokes and anti-stokes Raman scattering |
WO2006095343A1 (en) | 2005-03-10 | 2006-09-14 | Anatoly Babchenko | An optical sensor and a method of its use |
US8761865B2 (en) | 2005-03-10 | 2014-06-24 | Anatoly Babchenko | Optical sensor and a method of its use |
WO2007090147A2 (en) * | 2006-01-31 | 2007-08-09 | The Board Of Trustees Of The University Of Illinois | Method and apparatus for measurement of optical properties in tissue |
WO2007090147A3 (en) * | 2006-01-31 | 2008-08-07 | Univ Illinois | Method and apparatus for measurement of optical properties in tissue |
US8983580B2 (en) | 2008-01-18 | 2015-03-17 | The Board Of Trustees Of The University Of Illinois | Low-coherence interferometry and optical coherence tomography for image-guided surgical treatment of solid tumors |
US11779219B2 (en) | 2008-01-18 | 2023-10-10 | The Board Of Trustees Of The University Of Illinois | Low-coherence interferometry and optical coherence tomography for image-guided surgical treatment of solid tumors |
Also Published As
Publication number | Publication date |
---|---|
GB8818690D0 (en) | 1988-09-07 |
AU4053489A (en) | 1990-03-05 |
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