CA2159235C - Apparatus and method for measuring components in a bag - Google Patents
Apparatus and method for measuring components in a bag Download PDFInfo
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- CA2159235C CA2159235C CA002159235A CA2159235A CA2159235C CA 2159235 C CA2159235 C CA 2159235C CA 002159235 A CA002159235 A CA 002159235A CA 2159235 A CA2159235 A CA 2159235A CA 2159235 C CA2159235 C CA 2159235C
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- electromagnetic radiation
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- 238000000034 method Methods 0.000 title claims description 37
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- 235000015097 nutrients Nutrition 0.000 claims abstract description 17
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- 239000000306 component Substances 0.000 description 62
- 239000000203 mixture Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 230000003595 spectral effect Effects 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 14
- 238000004458 analytical method Methods 0.000 description 13
- 229940028435 intralipid Drugs 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- 239000008355 dextrose injection Substances 0.000 description 10
- 238000005259 measurement Methods 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 9
- 239000008121 dextrose Substances 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000002835 absorbance Methods 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 6
- 239000002960 lipid emulsion Substances 0.000 description 6
- 238000000513 principal component analysis Methods 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 239000008223 sterile water Substances 0.000 description 5
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 5
- 229910052721 tungsten Inorganic materials 0.000 description 5
- 239000010937 tungsten Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 239000013307 optical fiber Substances 0.000 description 4
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- 239000004800 polyvinyl chloride Substances 0.000 description 4
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- 238000002329 infrared spectrum Methods 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
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- 239000000126 substance Substances 0.000 description 3
- 238000002834 transmittance Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 2
- 229920000995 Spectralon Polymers 0.000 description 2
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- 229910052732 germanium Inorganic materials 0.000 description 2
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920000915 polyvinyl chloride Polymers 0.000 description 2
- 229960001309 procaine hydrochloride Drugs 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- -1 water Chemical class 0.000 description 2
- 241000208140 Acer Species 0.000 description 1
- 108010003320 Carboxyhemoglobin Proteins 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 1
- 241000357292 Monodactylus Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 108010064719 Oxyhemoglobins Proteins 0.000 description 1
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- OBOXTJCIIVUZEN-UHFFFAOYSA-N [C].[O] Chemical compound [C].[O] OBOXTJCIIVUZEN-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- YVPYQUNUQOZFHG-UHFFFAOYSA-N amidotrizoic acid Chemical compound CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I YVPYQUNUQOZFHG-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
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- 238000004590 computer program Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960005423 diatrizoate Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000005350 fused silica glass Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000000468 intravenous fat emulsion Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000012067 mathematical method Methods 0.000 description 1
- 238000013178 mathematical model Methods 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
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- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000003909 pattern recognition Methods 0.000 description 1
- 239000006223 plastic coating Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
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- 238000000411 transmission spectrum Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
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
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/47—Scattering, i.e. diffuse reflection
- G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
- G01N21/51—Scattering, i.e. diffuse reflection within a body or fluid inside a container, e.g. in an ampoule
-
- 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
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N2021/0364—Cuvette constructions flexible, compressible
-
- 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
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
Landscapes
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Pathology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Sorting Of Articles (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Examining Or Testing Airtightness (AREA)
- Supplying Of Containers To The Packaging Station (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
An apparatus for measuring components in a liquid medium, in particular parenteral nutrients, within a flexible transparent bag. A spacer is utilized to fix or determine the optical path across the bag chamber and includes a passage for electromagnetic radiation of selected wavelengths.
The source of electromagnetic radiation is capable of sending radiation into the bag chamber and to detector means which analyzes the radiation passed through or reflected from the components in the bag chamber.
The source of electromagnetic radiation is capable of sending radiation into the bag chamber and to detector means which analyzes the radiation passed through or reflected from the components in the bag chamber.
Description
215!235 S P E C I F I C A T I O N
TITLE
~~APPARATUS AND METHOD FOR
MEASURING COMPONENTS IN A BAG~~
HACRGROUND OF THE INVENTION
The present invention relates to a novel and useful apparatus and method for non-invasively analyzing l~.quid medium components in a bag.
Liquid compounds are often placed in bags for various purposes. For example, the use of total parenteral nutrients (TPN) which are eventually the source of intravenous feeding are stored in transparent or translucent flexible bags. TPN
compounds are commonly mixed in pharmacies using commerciall~~ available compounders which accept three or more TPN compounds and automatically mix these compounds into an appropriate container such as an intravenous (I. V. bag). Intravenous use of the bags usually takes place at a later time in a hospital or medical facility. Typical compounds include 70%
dextrose injection U.S.P., 10% Travasol (amino acid) injection, Intralipid 20% fat I.V. emulsion, sterile water, and moony others.
Presently, methods such as color coding are relied upon to avoid making errors during the compounding or mixing process. Different tubes feeding the I.V. k>ag possess connectors of different colors which correspond to the colors of the specific mixing positions an the compounder. For example, setting a red indicator on a compounder for 100 milliliters would deliver 100 milliliters from a starting bottle connected to the tubing line which possesses red connectors. However, there is no _2_ assurance that the correct compound was initially connected to the red tubing line.
Consequently, an incorrect connection of the tubing between bottles of dextrose solution and water, for example, may have dire consequences, such as death for patients with sugar intolerance.
j Many of the TPN compounds are clear liquids. That .is to say, water, amino acid injection, dextrose injection, and electrolytes are clear liquids precluding visual distinction among them. Furthermore, it is preferable to perform identification of TPN components non-invasively and rapidly to minimize potential contamination and to minimize analysis time by personnel.
An article entitled "Near Infrared Multi-Component Analysis of Parenteral Products Using The InfraAlyzer 400" by John J. rose 71-78, dated March-April 1892. examined meglumine and meglumine diatrizoate in 30% diatrizoate megluinine injections solutions using diffuse reflectance in the near infrared region.
The best combinations of three or four wavelength filters from nineteen ( 19) available wavelength filters were selected using multiple regression statistical methods. The specific wavelengths were not identified.
An article entitled "The Spectrophotemetrie Absorbance of Intral~id"
by Cane et al., pp. 53-55, dated 1980. develops calibrations for Intralipid in water in concentrations from 2.5 to 40 mg/mi at six (6) visible wavelengths between 505 and 626.6 nanometers. Intralipid interferes with spectrophotometric analysis of oxyhemoglobin, carboxyhemoglobin, and total hemoglobin.
A writing entitled, ''Simple Methods For The Quantitative Determination of Procaine Hydrochloride In Parenteral Products" by Das Gupta et al., pp. 408-410, dated July 1969. presents calibrations in the ultraviolet region of spectrophotometry. Specifically, the Das Gupta reference obtained calibrations at 228 nanometers for buffered solutions of procaine hydrochloride in the 0-20 microgram/ml concentration range.
An article entitled "Nonodestructive NIR and NIT Determination Of Protein, Fat, And Water In Plastic Wrapped Homo~eni:~ed Meat" by Tomas Isaksson et al., pp. 1685-1694, dated 1992. describes NIR measurements of proteins by diffuse reflectance in meat samples with and without plastic coatings. Samples were placed in a rubber cup prior to covering the meat sample with plastic laminant.
United States patents 4,800,279 and 5,002,397 describe methods and devices for visible and near-infrared evaluation of physical properties of samples.
United States patent 4,872,868 shows an. analyzer for collection bags which provides an envelope that permits the insertion of reagent's test strips and the like.
United States patents 3,857,485 and 3,924,128 teach a method of analyzing sample containers by liquid scintillation spectrometry which utilizes light transmission sealing means to prevent entry of ambient light or the escape of light from the photomultiplier tube detection devices.
United States patent 5,239,860 describes a sensor for continuously measuring alcohol and gasoline fuel mixtures in a clear TeflonTM tube using a predetermined optical path and electromagnetic radiation at a pair of wavelengths which are generated by rapidly switching currents through a light-source.
Thermopile detectors are used to detect an increase in temperature due to light transmitted through the flowing gasoline/alcohol mixture.
An apparatus and method for identifying solutions in a translucent transparent or semi-transparent plastic bag, such as parenteral nutrients, non-invasively, qualitatively and quantitatively would be a notable advance in the chemical analysis field.
SUMMARY OF THE Il\TSIEN'TION
In accordance with the present invention a novel and useful apparatus and method for identifying parenteral nutrients is herein provided.
Accordingly, in one aspect of the present invention there is provided an apparatus for measuring a component in a liquid medium within the chamber of a flexible translucent container formed by a wall portion, .comprising:
a. spacer means for sequentially determining a plurality of optical paths across the container wall portion and chamber, and the bag wall portion alone, said spacer means including a passage for electromagnetic radiation; and b. a source of electromagnetic radiation capable of directing electromagnetic radiation through said passage, through the wall portion of the container, and along any of said determined optical paths, said source of electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and c. detector means for analyzing said electromagnetic radiation after interaction with the components in the bag chamber and the wall portion of the bag.
According to another aspect of the present invention there is provided a method of analyzing components in a liquid medium within the chamber of a flexible bag comprising the steps of:
a. placing the bag in spacer means for determining the optical path across the bag chamber, said spacer means including a passage for electromagnetic radiation;
b. directing electromagnetic radiation from a source of electromagnetic radiation to the components in said bag chamber for interaction therewith; and c. analyzing said electromagnetic radiation with detector means after interaction of said electromagnetic radiation with the components in the bag chamber.
According to yet another aspect of the present invention there is provided an apparatus for detecting light scattering components in a liquid medium within the chamber of a flexible translucent bag formed by a wall portion, comprising:
a. a fence element, said fence element including a passage for electromagnetic radiation to the wall portion of the bag;
b. a source of electromagnetic radiation capable of directing electromagnetic radiation through said fence element passage, said source of -4a-electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and c. detector means for analyzing said electromagnetic radiation after interaction with the components in the bag chamber and the wall portion of the bag, said detector means receiving said electromagnetic radiation, after interaction with a component in the bag chamber, through said fence passage.
According to still yet another aspect of the present invention there is provided an apparatus for non-invasively identifying components in a liquid medium within an interior of a flexible bag, the apparatus comprising:
a source of electromagnetic radiation capable of directing electromagnetic radiation into the interior of the flexible bag, the source of electromagnetic radiation capable of interaction with the components in the flexible bag interior and the flexible bag;
optical detector means located outside the flexible bag receiving the electromagnetic radiation after interaction with the components in the flexible bag interior and the wall portion of the flexible bag and providing a signal indicative thereof; and means for analyzing the signal to identify the components of the liquid medium in the flexible bag.
The apparatus of the present invention employs spacer means for supporting a flexible transparent or translucent bag and for determining the optical path across the bag chamber. The spacer means includes a passage for electromagnetic radiation. The spacer means may take the form of a pair of rigid elements or fences and a mechanism for shortening or lengthening the distance between the rigid fences. The rigid fences may support the bag against vertical movement and also be capable of exerting compressive force on the bag to a precisely determined dimension between the rigid fences. Such dimension would correspond to a particular optical path, which may include the bag wall alone or the bag wall and the bag filled with components in a liquid medium.
A source of electromagnetic radiation directs electromagnetic radiation through the spacer passage and to the wall portion of the bag. The source of electromagnetic radiation may produce coherent light, ultraviolet radiation, x-rays, infrared raf~iatiory broad band radiation e.g., a tungsten sou~,rce, and the like.
Deaector means is also employed in the present invention for analyzing the electromagnetic radiation passed through the spacer passage and along a determined. optical path which is through a dimension of the bag chamber. In certain cases the optical path may pass completely across the bag such that the detector is receiving light which has been transmitted through the bag. In other cases, the detector may be placed on th.e same side of the bag as the source of electromagnetic radiation and receive light which has interacted with the contents of the bag by diffuse reflectance. Further, the detector may receive light by diffuse reflectance and/or by diffuse transflectance, i.e., where light passes through the bag and then is reflected back through the bag by a diffuse reflector or mirror located on the opposite side of the bag relative to the detector. It has been found that near-infrared radiation is particularly useful in detecting parenteral nutrients in a flexible I.V. bag. In addition, specific wavelengths, rather than a continuum of wavelengths, may be used as the radiation sought for analysis to enable the use of simpler and less expensive instrumentation comprised of several discrete detectors, each covered by a narrow wavelength filter. Fiber optics may also be utilized to carry light to and from the I.V. bag.
Mathematical models may be employed to quantitatively and qualitatively detect components within the I.V.
bag accurately and quickly.
Another adaption of the device of the present invention produces a self referencing device with respect: to the intensity. Specifically, transmittanc:e measurements may be taken of the bag alone, squeezed to eliminate a chamber and to expel the liquid components, and along a determined optical path of the bag filled with certain components.
Absorbance for a sample may be accurately determined under the Be'er's Law relationship. Chemical concentration can be directly related to an absorbance difference c>btained from a spectral measurement using two different path lengths. This technique minimizes or eliminates common spectroscopic measurement problems dues to contamination, changes in the spectroscopic windows holding the sample, instrument problems dues to temperature changes on internal optical elements, the source of electromagnetic radiation, a.nd the like.
It. may be apparent that a novel and useful apparatus far analyzing components in a liquid medium has been de~~cribec~.
It. is therefore an object of the present invention to provide an apparatus and method for analyzing liquid components in a flexible transparent or translucent container or without invading the integrity of the bag.
Another object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium within a flexible transparent or translucent container to prevent misuse of such components> in treating patients in a medical facility.
A further object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium :Found in a transparent or translucent plastic container wlz.ich is accurate and may include qualitative a:~ well as quantitative measurements of the components therein.
A further object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium found in a transparent or translucent flexible bag where such components are parenteral or enteral nutrients typically used for intravenous feeding.
A further object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium i=ound in a translucent flexible bag which is capable of detecting light from a source after interaction with the bag alone and after interaction with the bag and the components in the bag.
Another object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium within a flexible bag employing either transmittance or dif=fuse reflectance techniques.
According to one aspect of the invention, there is provided ar.. apparatus for measuring a component in a liquid medium within the chamber of a flexible translucent container formed by a wall portion comprising: s~~acer means for sequentially determining a plurality of optical. paths across the container wall portion and chamber, and the bag wall portion alone the spacer means including a passage for electromagnetic radiation; and. a source of electromagnetic radiation capable of dizectinc~ electromagnetic radiation through the spacer means pa~~sage, through the wall portion of the container, and. along any of the determined optical paths, 7a the source of electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and detector means for analyzing the electromagnetic radiation after interaction with the components in the b<~g chamber and the wall portion of the bag.
According to another aspect of the invention, there is provided a method of analyzing components in a liquid medium within the chamber of a flexible bag comprising the step: of: placing the bag in spacer means for determining the optical path across the bag chamber, the spacer means inc:iuding a passage for electromagnetic radiation; directing electromagnetic radiation from a source of electromagnetic radiation to the components in the bag chamber for .interaction therewith; and analyzing the electromagnetic radiation with detector means after interaction of~ the electromagnetic radiation with the components in the bag chamber.
Accc~rding to a further aspect of the invention, there is provided a method of analyzing components in a liquid medium within the chamber of a flexible bag in which the com~~onent:~ are parenteral and enteral nutrients.
According to yet a further aspect of the invention, there is provided an apparatus for detecting light scattering components in a liquid medium within the chamber of a flexible translucent bag formed by a wall portion comprising: a fence element, the fence element including a passage for electromagnetic radiation to the wall portion cf the bag; a source of electromagnetic radiation capable of: directing electromagnetic radiation through the fence element passage, the source of _. ~~".electromagnetic radiation being capable of interaction 7b with a component in 'the bag chamber and the wall portion of the bag; and detE=~~tor means for analyzing the electromagnetic radiation after interaction with the components in the b<~g chamber and the wall portion of the bag, the detector means receiving the electromagnetic radiation, after ini~eraction with a component in the bag chamber, through the fence passage.
According to yet another aspect of the invention, there is provided an apparatus for non-invasively idE~ntify_Lng components in a liquid medium within an interior of a flexible gas, the apparatus comprising: a source of electromagnetic radiation capable of directing electromagnetic radiation into the interior of the bag, the source of electromagnetic radiation capable of interaction with the components in the bag chamber and the bag; optical detector means located outside the bag rece:iving the electromagnetic radiation after interaction w~_th the components in the bag chamber and the wall portion of the bag and providing a signal indicative thereof; and means for analyzing the signal to identify the components of the liquid medium in the bag.
The invention possesses other objects and advantages es~~ecially as concerns particular characteristics and features thereof which will become apparent as tl-..e specification continues.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a sectional view of a first embodiment of the apparatus of the present invention.
A'~
_$_ FIG. 2 is a sectional view of the apparatus of Fig. 1 taken along line 2-2 of Fig. 1.
FIG. 2A is a sectional view taken along line 2A-2A of Figs. 2.
FIG. 2B is a sectional view of an I.V. bag collapsed by the apparatus of the present invention.
FIG. 3 is a side sectional view of another embodiment of the apparatus of the present invention.
FIG. 4 is a graphical representation with experimental results described in Example 1.
FIG. 5 is a graphical representation of the experimental results described in Example 2.
FIG. 6 is a graphical representation of experimental results described in Example 3.
FIG. 7 is a graphical representation of an experimental result described in Example 4.
FIG. 8 is a graphical representation of PCA
plot of scores described in Example 5.
FIGS. 9 and 10 are graphical representations depicting predictions using PLS analysis described in Example 4.
FIG. 11 is a graphical representation of a PLS model utilizing data found in Example 4.
FIGS. 12,, 13, and 14, are graphical representations of MLR methods applied to the data shown in Table 2 of Example 4.
FIG. 15 is a graphical representation of a step wise ML~R program utilizing the data of Table 1 of Example 4.
For a better understanding of the invention reference is made to the following detailed description of they preferred embodiments which should be referenced to t:he herein before described drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Various aspects of the present invention will evolve from the following detailed description of the preferred embodiments thereof which should be taken in conjunction with the herein before described drawings.
The invention as a whole is depicted in the drawings by reference character 10. The apparatus 10 is shown in the drawings as including multiple embodiments, denoted by the addition of an upper case letter. Referring to Fig. 1, apparatus lOA is depicted in which spacer means 12 is provided to hold a flexible transparent or semi transparent bag 14 in place. The term "translucent" is used herein to indicate a transparent, semi-transparent, or non- opaque bag. Bag 14 includes a chamber 16 which is capable of holding components in a liquid medium 18.
Liquid medium including such components 18 are passed through tube 20, shown partially in Fig. l, which is ultimately clamped or sealed when the bag 14 is filled. Bag 14 may take the form of a plastic intravenous bag (LV. bag) formed of polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), and like materials. However, other containers may be employed herein. The liquid medium and components 18 found within bag may consist of mixtures of parenteral or enteral nutrients which may be intravenously fed to a patient. For example, such nutrients may include sterile water, 70%
dextrose injection U.S.P., 10% TravasolTM (amino acid) Aminosyn or FreeAmine injection, IntralipiaTM 20% fat LV. emulsion, potassium chloride, and the like, individually or in various combinations.
Spacer means 12 includes a pair of elements 22 and 24 which are shown in Figs. 1 and 2 as a pair of solid fences placed in opposition to one another.
Fences 22 and 24 are slidingly supported by rods 26 and 28 which are supported to a surface by stands 30 and 32, depicted in phantom on Figs. 1 and 2. Rods 26 and 28 serve as a guide for fences 22 and 24. A
threaded screw 34 is fixed to fence 22 through a boss 36. Knurled wheel and bearing unit 38 is capable of turning relative to boss 36. The turning of wheel 38 also rotates. threaded connect screw 34 which threadingly engages a threaded bore 40 through fence 24. Thus, fence 22 is stationary relative to rods 26 and 28 whiles fence 24 is moveable thereto, manually or by motor means, such as a solenoid, directional arrow 25. Unit 38 serves to measure or to stop the relative movement of fencer 22 and 24, to determine the optical path through. bag 14 or sequentially determine a plurality of optical paths through bag 14. It should be noted that fences 22 and 24 may be hingedly attached to one another to determine the distance therebetween;, like a clamshell.
With reference to Fig. 2A, it maybe observed that such oP~tical path (O. P.) of components 18 within bag 14 may be easily adjusted by the movement of fence 24 relative to fence 22. The O.P. may vary between 1.0 millimeter to 15 millimeters in many cases. In certain instances, an empty bag 14 may be compressed by fences 22 and 24 such that walls 42 and 44 touch one another, Fig. 2B, eliminating chamber 16. This configuration is useful in obtaining a reference value for the bag without medium 18 in chamber 16. Inner surfaces 42 and 44 of fences 22 and 24, respectively also provide sufficient friction to prevent the slippage of bag 14 downwardly between fences 22 and 24. Of course, other structures may be employed to prevent the slippage of bag 14 within spacer means 12 such as a floor, or suspension device pulling upwardly on bag 14 while bag 14 is within spacer means 12, and the like.
Apparatus 10 further possesses a source of electromagnetic radiation 46. Source 46 may take the form of laser light, infrared radiation, ultraviolet radiation, visible radiation, or any other electromagnetic radiation found in the spectrum.
Light 46 is passed to bag chamber 16 through passage 48 in fence 22 and from chamber 16 of bag 14 through passage 50 of fence 24. Electromagnetic radiation from source 46 may be filtered by filter 52 and led to passage way 48 by optical fiber or fiber bundle 54.
Fitting 56 directs radiation from fiber optical bundle 54 to collimating lens 58. Parallel rays of electromagnetic radiation are then passed through bag 14 and liquid medium 18 containing various components to converging lens 60. Fitting 62 directs the electromagnetic radiation through optical fiber or fiber optic bundle 64 to a detector 66 for analysis.
Detector means 66 in its broadest sense may take the form of any suitable spectrophotometer, single or multiple detectors, or sources being appropriately filtered for the wavelength of interest, in combination 'with a computer employing an appropriate software program such as Gram 386, available from Galactic Industries, Inc. of Salem NH.
With reference to Fig. 3, embodiment lOB of the present invention is depicted. Apparatus 10B
possesses a pair of opposing elements or fences 68 and 70. As in Embodiment 10A, guide 72 may take the form of a pair oi.° rods supported by stands on a surface a hinged clamshell configuration or the like. Fence 68 is fixed to guide 72 while fence 70 is moved and the distance bei:ween fences 68 and 70 is set by threaded screws 74, in the same manner as threaded screw 34 found in embodiment 10A. Fence 68 includes a diffuse reflector 7t> on one side of bag 14 containing liquid medium 18 having various components therewithin. Of course, difi_.use reflector may be formed integrally with bag 14.. Diffuse reflector 76 may take the form of a white c:eramin disk or other suitable reflector.
Light from :source 46, not shown, passes through outer fiber or fixer bundle 78, from bag 14 containing a liquid medium having various components 18, and through fibE:r optic bundle 80, which is formed concentricaT.ly with fiber optic bundle 78. Analysis of the components within bag chamber 16 takes place by interaction of tha_ electromagnetic radiation from fiber optic bundle 78 by diffuse reflectance, by diffuse transflectance, in conjunction with diffuse reflector 7Ei, or a combination of both. The latter is especially useful where liquid medium is murky to an uncertain dE~gree. Such diffuse reflectance measurements may be obtained simply by pressing an I.V. bag fi7.led with light scattering material against fence 70 without the use of fence 68. Again, fiber optic bundlE~s 78 and 80 may be angularly disposed with respect to Each other i.e., 30 degrees, to minimize specular components of electromagnetic radiation reflected from bag 14.
The general operation of embodiments 10A and 10B takes place by supporting bag 14 within spacer means 12, which may include elements 22 and 24 of embodiment 1.OA, or fences 68 and 70 of embodiment 10B.
Spacer mean; 12 is then adjusted to solely determine the desired optical path within bag 14 or to sequentially determine the optical path through a plurality of bags such as bag 14. In general, where liquid medium 18 is not perfectly clear, as in the case of lipids, the optical path would be short. For murky light scattering liquids, it is unlikely that radiation will reach the far side of bag 14 and be reflected back from diffuse reflector or mirror 76.
In such a case, the space between fences 68 and 70 is not critical. The converse is true with clear liquid medium 18. Electromagnetic radiation from source 46 is then directed through passages 48 and 50 of elements 22 and 24, or simply directed through passage 82 of fence 70 of embodiment lOB. After interaction with the comaponents in a liquid medium 18, electromagnetic radiation is passed from bag 14 to detector 66 for analysis by a suitable software program in conjuncaion with a personal computer.
Where bag 14 is collapsed by fences 22 and 24, electromagnetic radiation may be passed through bag 14 to obtain a reference reading for use with spectral analyses of liquid in bag 14.
This spectroscopic method and apparatus of the present invention is capable of identifying and measuring many components in a liquid medium 18.
Colorless materials, such as parenteral nutrients have distinctive spectral characteristics in regions outside the visible electromagnetic spectrum (400-700nm). In particular, infrared (3000-25,OOOnm) regions of the electromagnetic spectrum produces distinctive spectral features arising from specific molecular structures that are characteristics of the compounds. Such features derive from molecular vibrations of bonded atoms such as oxygen-hydrogen, carbon-hydrogen, nitrogen-hydrogen, and oxygen-carbon.
Different types o1. carbon-hydrogen bonds can be distinguished, such as those arising from terminal C-H
groups or CH:3 groups, i.e., fundamental molecular vibrations. Similar features occur at multiples of these fundamental frequencies (i.e., shorter wavelengths) and, hence, commonly occurred in the near-infrared. These are referred to as vibrational overtones such as the first and second overtones of carbon-hydrogen near 1700 and 1100 nm, respectively.
Several different fundamental vibrations can combine to form a vibrational absorption at shorter wavelengths called a combination mode, ie., such as oxygen and h.ydrogE~n in molecular water near 1900nm.
Therefore, many regions of the electromagnetic spectrum may be used to obtain useful spectral data.
While in the foregoing, embodiments of the present invention have been set forth in considerable detail for the purposes of making a complete disclosure of the invention, it may be apparent to those of skill in the art that numerous changes may be made in such. detail without departing from the spirit and principles of the invention. Further description of the invention is contained in the following examples.
Th.e following examples are described in detail herein for the purpose of illustration of the present invention, but are not deemed to limit the scope of the invention herein.
The near infrared spectra of several parental nutrient compounds, i.e., water, 70% dextrose injection USP and 10% Travasol amino acid injection was measured individually or in various combinations to illustrate specaral characteristics. Such compounds formed an optically clear solution, which was placed in a fused quartz cuvette having an optical path of one (1) millimeter. The spectral data were acquired with a germanium detector found in a spectrophotometer, Model 200, manufactured by Guided Wave, Inc. of El L)orado Hills, California. Two (2) one meter long, 50U micron core diameter, silica-clad low-OH optical fibers and collimating lenses were connected to the sspectrophotometer. Collimating lenses were placed between one end of each fiber and the cuvette. One fiber transmitted light from the tungsten light source inside the spectrophotometer through collimating lens and cuvette. The second collimating lens received light passing through the cuvette and focused the light into the second fiber, which transmitted the light back to the monochrometer and detector in the spectrophotometer. The absorbance characteristics obtained are charted in Fig. 4. Water reaches a maximum absorbance between 1400 and 1500 nanometers. The remaining components produce additional changes on the long wavelength side of the main water peak in the 1500-1800 nanometer region in Fig. 4.
A polyvinyl chloride bag used for intravenous feeding (IV bag) was filled with sterile water, 70% dextrose injection, USP, and 10% Travasol amino acid injection, which are typical parenteral nutrients. These components formed an optically clear solution. Utilizing the apparatus shown in Fig. 1, spectral data were attained with a germanium detector found in a spectrophotometer distributed by Guided Wave, Inc. under the designation model 200. A pair of one meter long, 500 micron core diameter, silica-clad low-OH optical fiber and collimating lenses were employed with the subject detector. The IV bag was compressed to an optical path of 15 millimeters.
Distinguishing characteristics were uncovered in the compounds within the I.V. bag in the 800 to 1100 nanometer region of an electromagnetic source of radiation. Reference analysis was also performed on an empty I.V. bag. Fig. 5 represents the results of this analysis. EXAMPLE 3 The parenteral compounds of Examples 1 and 2 were placed in an I.V. bag with the addition of a common 20% Intralipid intravenous fat emulsion (I. V.
fat emulsion). The final mixture of nutrients included fat compounds occupying less than 50% of the volume of the I.V. bag mixture. Fig. 6 shows that, in spite of the light. scattering characteristics of the milky solution found in the IV bag containing the fat compounds, transmission may still be performed through 1-2 millimeters of an optical path of the bag. In other words, the bag shown in Fig. 6 represents a squeezing of the bag to a smaller optical path, (1.5 to 2 millimeters) than the optical path represented in Fig. 5. It is estimated that 95% of the light passed through thc~ bag in. this Example was scattered and lost through the first millimeter of the optical path.
Various mixtures o~f 70$ dextrose injection USP, 20%
Intralipid I.V. fat emulsion, 10% Travasol, and water are employed and are identified on Fig. 6. The absorbance characteristics are clearly identifiable for each mixture in which changes in the intensity of the water peak near 1450 nm, effects due to amino acids and dextrose in the 1500-1700 nm region, and contribution from lipid near 1200 nm are identifiable.
As will be shown from diffuse reflectance spectral data hereinafter in Example 4, these features can be used to perform quantitative analysis of the mixtures in the bag.
The apparatus shown in Fig. 3 was employed to conduct diffuse: reflectant/transmittance measurements through I.V. bags constructed of polyvinyl chloride (PVC) filled with mixtures of parenteral nutrients. The mixtures were composed of 20~ Intralipid I.V. fat emulsion, 10% Travasol (amino acid injection solution), 70o dextrose injection solution, and sterile water. Nutrients were measured volumetrically with a graduated cylinder mixed, and placed in one (1) liter PVC I.V. bags. The device depicted in Fig. 3 was set to provide an optical path, excluding the thickness of the I.V. bag material, of about 15 millimeters through the solution in the filled I.V. bag. The set screw spacer means 12, Fig.
1, was employed to compress the bag to this particular optical path setting. Since these mixtures all contained lipid and hence, scattered light suitable for diffuse reflectance measurements, the space set for the optical path was not critical to the measurement. A spectrophotometer was employed, similar to t:he spectrophotometer utilized in Example 1 using an Inc~aAs detector. The source of light was a tungsten lamp. The light was delivered through a 6 mm dia hole in a white Spectralon block available from Labsphere, 7:nc., North Sutton, NH from a 20 watt tungsten source. This block was attached to the stationary fence '70 in Fig. 3. A bundle of 10 individual fibers of the type described in Example 1 were cementE:d into a small metal fitting and inserted through the Spectralon block at 30 degrees to the hole containing t:he tungsten light source. The end of the fiber bundle fitting was coincident with the end of the block in contact with the IV bag. Near infrared spectra werE~ collE~cted between 1100 and 1650 nanometers. Fig. 7 depicts the results obtained where the various mixtures used were clearly recognizable, with the exception of the 75:25 Travasol and lipid mixture, which, generally, is only slightly different from the 75:25 water and lipid mixture.
The spectral differences shown in Fig. 7 can be quantified with the commonly used method of Principal Component Analysis (PCA). PCA is essentially a pattern recognition procedure that can assign one number to the entire spectrum employed in the analysis,. PCA is accomplished by analyzing all spectral data of all samples in determining the linear combination of data that explains the largest variation of spectral information. A different linear combination is ne};t determined that shows the next largest variation in the spectral data. The linear combinations: are determined in this way. Each linear combination is referred to as a FACTOR which provides co-efficient: that multiply the data at each wavelength. The product of this multiplication is summed to dsaermine one number which is referred to as a SCORE. Thus, by plotting SCORES from FACTOR I
against those from FACTOR II, samples can be distinguished or identified. In mathematical terms, FACTORS are a set of orthogonal eigenvectors whose lengths represent the percentage of variation in spectral data. SCORES are obtained by multiplying the elements of each e~igenvector, referred to as a LOADING
(each of which is a co-efficient for the spectral data at a specific wavelength) times the absorbance at that wavelength, and summing the results. Essentially, each sample is projected on each eigenvector and the distance from the origin i.e., the intersection of all eigenvector~; is thus measured. Other mathematical methods exi~,t for the purposes of identification of data, includling the computation of direction cosines, factor analysis, and cluster analysis. Referring to Fig. 8, a PC'A plot is illustrated using SCORES from the first two FACTORS of the diffuse reflectance data from the samples presented in Fig. 7. Table 1 herein represents the volume fraction of the nutrients employed in the preparation of Fig. 8:
TABLE I
10% STERILE 70% 20%
SAMPLE _TRAVASOL WATER DEXTROSE INTRALIPID
1 0.50 0.50 2 0. 50 0. 50 3 0.50 0.50 4 0.85 0.15 5 O.B5 0.15 6 0.85 0.15 7 0.75 0.25 8 0.75 0.25 9 0.'75 0.25 10 0.'75 0.25 11 0.75 0.25 12 0.75 0.25 13 0..25 0.25 0.25 0.25 14 0..25 0.25 0.25 0.25 These two f,~ctors account for 970 of the spectral variation among all of the samples, each identified by a sample nw:nber with a circle around the same. The 70% dextrose injection USP, water, and l0% Travasol amino acid injection components are clearly distinguished by the solid lines of Fig. 8. The 20%
intralipid fat emulsion content is also clearly shown by the three dashed lines representing 15%, 25%, and 50% intrali~~id. The solid Travasol and water lines lie closer to one another, but are significantly spaced from the dextrose line in Fig. 8. Such a relationship corresponds to spectral data in which water and T:ravasol are more similar to each other than dextrose. repeated measurements on the same IV bag showed reasonable reproductibility, i.e., samples 7 and 8 and s~~mples 11 and 12 of Fig. 8.
P~~rtial-Least Squares (PLS) method was also employed in the diffuse reflectance method for the samples shown in Fig. 8. The results of this method are shown in Figs. 9-10 of the present invention.
Partial-Least Squares (PLS) multivariate procedure is commonly used to determine chemical or physical property information from spectral data. Computer programs such as L1NSCRAMBLER are available from Camo of Norway. SPECTRACALC, and GRAMS/386 are available from Galactic Industries, Inc., of Salem, New Hampshire. Pirouette is available from Infometrics of Redmond, Wa~.hington. GRAMS/386 was used in the present analysis with a personal computer. PLS
incorporate~~ the benefits of PCA and attempts to provide a model of. the data with as few a number of FACTORS as is needed. A six FACTOR PLS model of the diffuse reflectance data of Table I represents a strong indication that mixtures in IV bags can be analyzed nom-invasively. Figs. 9 and 10 show predictions of 70°-<> dextrose injection and 20%
intralipid IV fat emulsion.
PL~S ana7.ysis of the one millimeter optical path using transmission through cuvettes, shown in Fig. 4 for samples without fat emulsion, also produced excellent quantitative results. The prediction for 70% dextrose injecaion USP in the mixture from a five FACTOR PLS model as presented in Fig. 11. The standard error of calibration for the sample set was 5%. The PLS, model in Fig. 11 utilized all spectral information from all samples as seen in Fig. 4.
Since it is often desirable to use a simple system comprising only a few wave lengths for quantitative analysis, a multi linear Regression Method (MLR) can also be used to predict physical properties of liquids and solids and analyze mixtures from near infrared spectra. MLR was performed on the one millimeter transmission spectra shown in Fig. 4.
The result :in calibration are presented in Figs. 12, 13, and 14, for 70~ dextrose injection USP, sterile water, and :LOS Travasol amino acid injection, respectivel~~. The data were generated by employing 2, 3, and 5 wa~~elengths between 1100 and 1800 nanometers, respectivel~t. This data are shown in Table 2 as follows:
TABLE II
70°~ DEXTRO:iE WATER 10% TRAVASOL
SAMPLE ACT._ PRED. ACT. PRED. ACT. PRED.
1 0.000 0.007 0.000 0.014 1.000 1.003 2 0.000 -0.005 1.000 0.977 0.000 0.072 3 1.000 0.986 0.000 -0.041 0.000 -0.061 4 0.000 0.008 0.500 0.468 0.500 0.475 5 0.500 0.522 0.500 0.517 0.000 -0.063 6 0.500 0.489 0.000 0.038 0.500 0.524 7 0.333 0.344 0.333 0.310 0.333 0.307 8 0.6fi7 0.681 0.166 0.128 0.166 0.241 9 0.1(>6 0.156 0.166 0.198 0.667 0.675 10 0.1(>6 0.162 0.667 0.653 0.167 0.149 11 0.700 0.697 0.300 0.306 0.000 0.052 12 0.2~i0 0.240 0.500 0.488 0.250 0.219 13 0.300 0.308 0.700 0.747 0.000 0.057 14 0.400 0.399 0.200 0.209 0.400 0.352 15 0.000 -0.007 0.300 0.320 0.700 0.683 Wavelen _c~th nm c:oeff. Waveln. Waveln. Coeff.
Coeff.
156 6 L6.21 1528 3.5355 1533 -51.3572 1716 --5.374:1 1716 -104.7859 1778 56.0781 Offset --4.9432 1744 98.6863 1287 194.9018 Mult. 0.99378 Offs et -3.4804 1193 668.3302 R -SEC 0.0347 Mult . R 0.99521 1194 455.3483 SEC 0.0306 Offset 9.8891 Mult.R 0.98888 SEC 0.0548 As may be observed, lengths of wave 1566 and nanomet ers were for dextrose. The employed wavelengths water and employed Travasol for are also indicated he indication is thata on TablE~
2. T
simpler and less ve system ng several expensi havi discrete dei:.ectors, each covered by a narrow wavelength :Filter or a device having means to switch between several discrete wavelengths, could be built to quantitai=ively predict the composition of mixtures as these shown in Fig. 4.
A stepwise multiple linear regression program was also 'used to determine a small set of wavelengths which could be used to predict the intralipid <ind 70% dextrose mixture in IV bags filled with the samples identified in Table II, analyzed by the embodiment of l0A of Fig. 1 (transmittance). The optical path was set to a distance of approximately 1.6 mm. Aci:ual versus predicted values were plotted as shown on Fig. 15. It should be noted that a perfect calibration would plot on the diagonal l~.ne found in Fic~. 15. Three (3) and five (5) wavelengths were used to produce excellent fits with standard errors of pi~ediction of 2.1 and 3.7% for the 20%
intralipid component and the 70% dextrose component in the mixture,, respectively. The three (3) wavelengths used for thc: 20% intralipid were 1606, 1536, and 1532 nanometers which .are listed in decreasing order of importance. Similarly, the five (5) lengths employed for the 70% dextrose were 1414, 1610, 1212, 1424, and 1200 nanomei~ers, also listed in order of importance.
Each mathem<~tical solution also included a constant term.
TITLE
~~APPARATUS AND METHOD FOR
MEASURING COMPONENTS IN A BAG~~
HACRGROUND OF THE INVENTION
The present invention relates to a novel and useful apparatus and method for non-invasively analyzing l~.quid medium components in a bag.
Liquid compounds are often placed in bags for various purposes. For example, the use of total parenteral nutrients (TPN) which are eventually the source of intravenous feeding are stored in transparent or translucent flexible bags. TPN
compounds are commonly mixed in pharmacies using commerciall~~ available compounders which accept three or more TPN compounds and automatically mix these compounds into an appropriate container such as an intravenous (I. V. bag). Intravenous use of the bags usually takes place at a later time in a hospital or medical facility. Typical compounds include 70%
dextrose injection U.S.P., 10% Travasol (amino acid) injection, Intralipid 20% fat I.V. emulsion, sterile water, and moony others.
Presently, methods such as color coding are relied upon to avoid making errors during the compounding or mixing process. Different tubes feeding the I.V. k>ag possess connectors of different colors which correspond to the colors of the specific mixing positions an the compounder. For example, setting a red indicator on a compounder for 100 milliliters would deliver 100 milliliters from a starting bottle connected to the tubing line which possesses red connectors. However, there is no _2_ assurance that the correct compound was initially connected to the red tubing line.
Consequently, an incorrect connection of the tubing between bottles of dextrose solution and water, for example, may have dire consequences, such as death for patients with sugar intolerance.
j Many of the TPN compounds are clear liquids. That .is to say, water, amino acid injection, dextrose injection, and electrolytes are clear liquids precluding visual distinction among them. Furthermore, it is preferable to perform identification of TPN components non-invasively and rapidly to minimize potential contamination and to minimize analysis time by personnel.
An article entitled "Near Infrared Multi-Component Analysis of Parenteral Products Using The InfraAlyzer 400" by John J. rose 71-78, dated March-April 1892. examined meglumine and meglumine diatrizoate in 30% diatrizoate megluinine injections solutions using diffuse reflectance in the near infrared region.
The best combinations of three or four wavelength filters from nineteen ( 19) available wavelength filters were selected using multiple regression statistical methods. The specific wavelengths were not identified.
An article entitled "The Spectrophotemetrie Absorbance of Intral~id"
by Cane et al., pp. 53-55, dated 1980. develops calibrations for Intralipid in water in concentrations from 2.5 to 40 mg/mi at six (6) visible wavelengths between 505 and 626.6 nanometers. Intralipid interferes with spectrophotometric analysis of oxyhemoglobin, carboxyhemoglobin, and total hemoglobin.
A writing entitled, ''Simple Methods For The Quantitative Determination of Procaine Hydrochloride In Parenteral Products" by Das Gupta et al., pp. 408-410, dated July 1969. presents calibrations in the ultraviolet region of spectrophotometry. Specifically, the Das Gupta reference obtained calibrations at 228 nanometers for buffered solutions of procaine hydrochloride in the 0-20 microgram/ml concentration range.
An article entitled "Nonodestructive NIR and NIT Determination Of Protein, Fat, And Water In Plastic Wrapped Homo~eni:~ed Meat" by Tomas Isaksson et al., pp. 1685-1694, dated 1992. describes NIR measurements of proteins by diffuse reflectance in meat samples with and without plastic coatings. Samples were placed in a rubber cup prior to covering the meat sample with plastic laminant.
United States patents 4,800,279 and 5,002,397 describe methods and devices for visible and near-infrared evaluation of physical properties of samples.
United States patent 4,872,868 shows an. analyzer for collection bags which provides an envelope that permits the insertion of reagent's test strips and the like.
United States patents 3,857,485 and 3,924,128 teach a method of analyzing sample containers by liquid scintillation spectrometry which utilizes light transmission sealing means to prevent entry of ambient light or the escape of light from the photomultiplier tube detection devices.
United States patent 5,239,860 describes a sensor for continuously measuring alcohol and gasoline fuel mixtures in a clear TeflonTM tube using a predetermined optical path and electromagnetic radiation at a pair of wavelengths which are generated by rapidly switching currents through a light-source.
Thermopile detectors are used to detect an increase in temperature due to light transmitted through the flowing gasoline/alcohol mixture.
An apparatus and method for identifying solutions in a translucent transparent or semi-transparent plastic bag, such as parenteral nutrients, non-invasively, qualitatively and quantitatively would be a notable advance in the chemical analysis field.
SUMMARY OF THE Il\TSIEN'TION
In accordance with the present invention a novel and useful apparatus and method for identifying parenteral nutrients is herein provided.
Accordingly, in one aspect of the present invention there is provided an apparatus for measuring a component in a liquid medium within the chamber of a flexible translucent container formed by a wall portion, .comprising:
a. spacer means for sequentially determining a plurality of optical paths across the container wall portion and chamber, and the bag wall portion alone, said spacer means including a passage for electromagnetic radiation; and b. a source of electromagnetic radiation capable of directing electromagnetic radiation through said passage, through the wall portion of the container, and along any of said determined optical paths, said source of electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and c. detector means for analyzing said electromagnetic radiation after interaction with the components in the bag chamber and the wall portion of the bag.
According to another aspect of the present invention there is provided a method of analyzing components in a liquid medium within the chamber of a flexible bag comprising the steps of:
a. placing the bag in spacer means for determining the optical path across the bag chamber, said spacer means including a passage for electromagnetic radiation;
b. directing electromagnetic radiation from a source of electromagnetic radiation to the components in said bag chamber for interaction therewith; and c. analyzing said electromagnetic radiation with detector means after interaction of said electromagnetic radiation with the components in the bag chamber.
According to yet another aspect of the present invention there is provided an apparatus for detecting light scattering components in a liquid medium within the chamber of a flexible translucent bag formed by a wall portion, comprising:
a. a fence element, said fence element including a passage for electromagnetic radiation to the wall portion of the bag;
b. a source of electromagnetic radiation capable of directing electromagnetic radiation through said fence element passage, said source of -4a-electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and c. detector means for analyzing said electromagnetic radiation after interaction with the components in the bag chamber and the wall portion of the bag, said detector means receiving said electromagnetic radiation, after interaction with a component in the bag chamber, through said fence passage.
According to still yet another aspect of the present invention there is provided an apparatus for non-invasively identifying components in a liquid medium within an interior of a flexible bag, the apparatus comprising:
a source of electromagnetic radiation capable of directing electromagnetic radiation into the interior of the flexible bag, the source of electromagnetic radiation capable of interaction with the components in the flexible bag interior and the flexible bag;
optical detector means located outside the flexible bag receiving the electromagnetic radiation after interaction with the components in the flexible bag interior and the wall portion of the flexible bag and providing a signal indicative thereof; and means for analyzing the signal to identify the components of the liquid medium in the flexible bag.
The apparatus of the present invention employs spacer means for supporting a flexible transparent or translucent bag and for determining the optical path across the bag chamber. The spacer means includes a passage for electromagnetic radiation. The spacer means may take the form of a pair of rigid elements or fences and a mechanism for shortening or lengthening the distance between the rigid fences. The rigid fences may support the bag against vertical movement and also be capable of exerting compressive force on the bag to a precisely determined dimension between the rigid fences. Such dimension would correspond to a particular optical path, which may include the bag wall alone or the bag wall and the bag filled with components in a liquid medium.
A source of electromagnetic radiation directs electromagnetic radiation through the spacer passage and to the wall portion of the bag. The source of electromagnetic radiation may produce coherent light, ultraviolet radiation, x-rays, infrared raf~iatiory broad band radiation e.g., a tungsten sou~,rce, and the like.
Deaector means is also employed in the present invention for analyzing the electromagnetic radiation passed through the spacer passage and along a determined. optical path which is through a dimension of the bag chamber. In certain cases the optical path may pass completely across the bag such that the detector is receiving light which has been transmitted through the bag. In other cases, the detector may be placed on th.e same side of the bag as the source of electromagnetic radiation and receive light which has interacted with the contents of the bag by diffuse reflectance. Further, the detector may receive light by diffuse reflectance and/or by diffuse transflectance, i.e., where light passes through the bag and then is reflected back through the bag by a diffuse reflector or mirror located on the opposite side of the bag relative to the detector. It has been found that near-infrared radiation is particularly useful in detecting parenteral nutrients in a flexible I.V. bag. In addition, specific wavelengths, rather than a continuum of wavelengths, may be used as the radiation sought for analysis to enable the use of simpler and less expensive instrumentation comprised of several discrete detectors, each covered by a narrow wavelength filter. Fiber optics may also be utilized to carry light to and from the I.V. bag.
Mathematical models may be employed to quantitatively and qualitatively detect components within the I.V.
bag accurately and quickly.
Another adaption of the device of the present invention produces a self referencing device with respect: to the intensity. Specifically, transmittanc:e measurements may be taken of the bag alone, squeezed to eliminate a chamber and to expel the liquid components, and along a determined optical path of the bag filled with certain components.
Absorbance for a sample may be accurately determined under the Be'er's Law relationship. Chemical concentration can be directly related to an absorbance difference c>btained from a spectral measurement using two different path lengths. This technique minimizes or eliminates common spectroscopic measurement problems dues to contamination, changes in the spectroscopic windows holding the sample, instrument problems dues to temperature changes on internal optical elements, the source of electromagnetic radiation, a.nd the like.
It. may be apparent that a novel and useful apparatus far analyzing components in a liquid medium has been de~~cribec~.
It. is therefore an object of the present invention to provide an apparatus and method for analyzing liquid components in a flexible transparent or translucent container or without invading the integrity of the bag.
Another object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium within a flexible transparent or translucent container to prevent misuse of such components> in treating patients in a medical facility.
A further object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium :Found in a transparent or translucent plastic container wlz.ich is accurate and may include qualitative a:~ well as quantitative measurements of the components therein.
A further object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium found in a transparent or translucent flexible bag where such components are parenteral or enteral nutrients typically used for intravenous feeding.
A further object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium i=ound in a translucent flexible bag which is capable of detecting light from a source after interaction with the bag alone and after interaction with the bag and the components in the bag.
Another object of the present invention is to provide a method and apparatus for analyzing components in a liquid medium within a flexible bag employing either transmittance or dif=fuse reflectance techniques.
According to one aspect of the invention, there is provided ar.. apparatus for measuring a component in a liquid medium within the chamber of a flexible translucent container formed by a wall portion comprising: s~~acer means for sequentially determining a plurality of optical. paths across the container wall portion and chamber, and the bag wall portion alone the spacer means including a passage for electromagnetic radiation; and. a source of electromagnetic radiation capable of dizectinc~ electromagnetic radiation through the spacer means pa~~sage, through the wall portion of the container, and. along any of the determined optical paths, 7a the source of electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and detector means for analyzing the electromagnetic radiation after interaction with the components in the b<~g chamber and the wall portion of the bag.
According to another aspect of the invention, there is provided a method of analyzing components in a liquid medium within the chamber of a flexible bag comprising the step: of: placing the bag in spacer means for determining the optical path across the bag chamber, the spacer means inc:iuding a passage for electromagnetic radiation; directing electromagnetic radiation from a source of electromagnetic radiation to the components in the bag chamber for .interaction therewith; and analyzing the electromagnetic radiation with detector means after interaction of~ the electromagnetic radiation with the components in the bag chamber.
Accc~rding to a further aspect of the invention, there is provided a method of analyzing components in a liquid medium within the chamber of a flexible bag in which the com~~onent:~ are parenteral and enteral nutrients.
According to yet a further aspect of the invention, there is provided an apparatus for detecting light scattering components in a liquid medium within the chamber of a flexible translucent bag formed by a wall portion comprising: a fence element, the fence element including a passage for electromagnetic radiation to the wall portion cf the bag; a source of electromagnetic radiation capable of: directing electromagnetic radiation through the fence element passage, the source of _. ~~".electromagnetic radiation being capable of interaction 7b with a component in 'the bag chamber and the wall portion of the bag; and detE=~~tor means for analyzing the electromagnetic radiation after interaction with the components in the b<~g chamber and the wall portion of the bag, the detector means receiving the electromagnetic radiation, after ini~eraction with a component in the bag chamber, through the fence passage.
According to yet another aspect of the invention, there is provided an apparatus for non-invasively idE~ntify_Lng components in a liquid medium within an interior of a flexible gas, the apparatus comprising: a source of electromagnetic radiation capable of directing electromagnetic radiation into the interior of the bag, the source of electromagnetic radiation capable of interaction with the components in the bag chamber and the bag; optical detector means located outside the bag rece:iving the electromagnetic radiation after interaction w~_th the components in the bag chamber and the wall portion of the bag and providing a signal indicative thereof; and means for analyzing the signal to identify the components of the liquid medium in the bag.
The invention possesses other objects and advantages es~~ecially as concerns particular characteristics and features thereof which will become apparent as tl-..e specification continues.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a sectional view of a first embodiment of the apparatus of the present invention.
A'~
_$_ FIG. 2 is a sectional view of the apparatus of Fig. 1 taken along line 2-2 of Fig. 1.
FIG. 2A is a sectional view taken along line 2A-2A of Figs. 2.
FIG. 2B is a sectional view of an I.V. bag collapsed by the apparatus of the present invention.
FIG. 3 is a side sectional view of another embodiment of the apparatus of the present invention.
FIG. 4 is a graphical representation with experimental results described in Example 1.
FIG. 5 is a graphical representation of the experimental results described in Example 2.
FIG. 6 is a graphical representation of experimental results described in Example 3.
FIG. 7 is a graphical representation of an experimental result described in Example 4.
FIG. 8 is a graphical representation of PCA
plot of scores described in Example 5.
FIGS. 9 and 10 are graphical representations depicting predictions using PLS analysis described in Example 4.
FIG. 11 is a graphical representation of a PLS model utilizing data found in Example 4.
FIGS. 12,, 13, and 14, are graphical representations of MLR methods applied to the data shown in Table 2 of Example 4.
FIG. 15 is a graphical representation of a step wise ML~R program utilizing the data of Table 1 of Example 4.
For a better understanding of the invention reference is made to the following detailed description of they preferred embodiments which should be referenced to t:he herein before described drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Various aspects of the present invention will evolve from the following detailed description of the preferred embodiments thereof which should be taken in conjunction with the herein before described drawings.
The invention as a whole is depicted in the drawings by reference character 10. The apparatus 10 is shown in the drawings as including multiple embodiments, denoted by the addition of an upper case letter. Referring to Fig. 1, apparatus lOA is depicted in which spacer means 12 is provided to hold a flexible transparent or semi transparent bag 14 in place. The term "translucent" is used herein to indicate a transparent, semi-transparent, or non- opaque bag. Bag 14 includes a chamber 16 which is capable of holding components in a liquid medium 18.
Liquid medium including such components 18 are passed through tube 20, shown partially in Fig. l, which is ultimately clamped or sealed when the bag 14 is filled. Bag 14 may take the form of a plastic intravenous bag (LV. bag) formed of polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), and like materials. However, other containers may be employed herein. The liquid medium and components 18 found within bag may consist of mixtures of parenteral or enteral nutrients which may be intravenously fed to a patient. For example, such nutrients may include sterile water, 70%
dextrose injection U.S.P., 10% TravasolTM (amino acid) Aminosyn or FreeAmine injection, IntralipiaTM 20% fat LV. emulsion, potassium chloride, and the like, individually or in various combinations.
Spacer means 12 includes a pair of elements 22 and 24 which are shown in Figs. 1 and 2 as a pair of solid fences placed in opposition to one another.
Fences 22 and 24 are slidingly supported by rods 26 and 28 which are supported to a surface by stands 30 and 32, depicted in phantom on Figs. 1 and 2. Rods 26 and 28 serve as a guide for fences 22 and 24. A
threaded screw 34 is fixed to fence 22 through a boss 36. Knurled wheel and bearing unit 38 is capable of turning relative to boss 36. The turning of wheel 38 also rotates. threaded connect screw 34 which threadingly engages a threaded bore 40 through fence 24. Thus, fence 22 is stationary relative to rods 26 and 28 whiles fence 24 is moveable thereto, manually or by motor means, such as a solenoid, directional arrow 25. Unit 38 serves to measure or to stop the relative movement of fencer 22 and 24, to determine the optical path through. bag 14 or sequentially determine a plurality of optical paths through bag 14. It should be noted that fences 22 and 24 may be hingedly attached to one another to determine the distance therebetween;, like a clamshell.
With reference to Fig. 2A, it maybe observed that such oP~tical path (O. P.) of components 18 within bag 14 may be easily adjusted by the movement of fence 24 relative to fence 22. The O.P. may vary between 1.0 millimeter to 15 millimeters in many cases. In certain instances, an empty bag 14 may be compressed by fences 22 and 24 such that walls 42 and 44 touch one another, Fig. 2B, eliminating chamber 16. This configuration is useful in obtaining a reference value for the bag without medium 18 in chamber 16. Inner surfaces 42 and 44 of fences 22 and 24, respectively also provide sufficient friction to prevent the slippage of bag 14 downwardly between fences 22 and 24. Of course, other structures may be employed to prevent the slippage of bag 14 within spacer means 12 such as a floor, or suspension device pulling upwardly on bag 14 while bag 14 is within spacer means 12, and the like.
Apparatus 10 further possesses a source of electromagnetic radiation 46. Source 46 may take the form of laser light, infrared radiation, ultraviolet radiation, visible radiation, or any other electromagnetic radiation found in the spectrum.
Light 46 is passed to bag chamber 16 through passage 48 in fence 22 and from chamber 16 of bag 14 through passage 50 of fence 24. Electromagnetic radiation from source 46 may be filtered by filter 52 and led to passage way 48 by optical fiber or fiber bundle 54.
Fitting 56 directs radiation from fiber optical bundle 54 to collimating lens 58. Parallel rays of electromagnetic radiation are then passed through bag 14 and liquid medium 18 containing various components to converging lens 60. Fitting 62 directs the electromagnetic radiation through optical fiber or fiber optic bundle 64 to a detector 66 for analysis.
Detector means 66 in its broadest sense may take the form of any suitable spectrophotometer, single or multiple detectors, or sources being appropriately filtered for the wavelength of interest, in combination 'with a computer employing an appropriate software program such as Gram 386, available from Galactic Industries, Inc. of Salem NH.
With reference to Fig. 3, embodiment lOB of the present invention is depicted. Apparatus 10B
possesses a pair of opposing elements or fences 68 and 70. As in Embodiment 10A, guide 72 may take the form of a pair oi.° rods supported by stands on a surface a hinged clamshell configuration or the like. Fence 68 is fixed to guide 72 while fence 70 is moved and the distance bei:ween fences 68 and 70 is set by threaded screws 74, in the same manner as threaded screw 34 found in embodiment 10A. Fence 68 includes a diffuse reflector 7t> on one side of bag 14 containing liquid medium 18 having various components therewithin. Of course, difi_.use reflector may be formed integrally with bag 14.. Diffuse reflector 76 may take the form of a white c:eramin disk or other suitable reflector.
Light from :source 46, not shown, passes through outer fiber or fixer bundle 78, from bag 14 containing a liquid medium having various components 18, and through fibE:r optic bundle 80, which is formed concentricaT.ly with fiber optic bundle 78. Analysis of the components within bag chamber 16 takes place by interaction of tha_ electromagnetic radiation from fiber optic bundle 78 by diffuse reflectance, by diffuse transflectance, in conjunction with diffuse reflector 7Ei, or a combination of both. The latter is especially useful where liquid medium is murky to an uncertain dE~gree. Such diffuse reflectance measurements may be obtained simply by pressing an I.V. bag fi7.led with light scattering material against fence 70 without the use of fence 68. Again, fiber optic bundlE~s 78 and 80 may be angularly disposed with respect to Each other i.e., 30 degrees, to minimize specular components of electromagnetic radiation reflected from bag 14.
The general operation of embodiments 10A and 10B takes place by supporting bag 14 within spacer means 12, which may include elements 22 and 24 of embodiment 1.OA, or fences 68 and 70 of embodiment 10B.
Spacer mean; 12 is then adjusted to solely determine the desired optical path within bag 14 or to sequentially determine the optical path through a plurality of bags such as bag 14. In general, where liquid medium 18 is not perfectly clear, as in the case of lipids, the optical path would be short. For murky light scattering liquids, it is unlikely that radiation will reach the far side of bag 14 and be reflected back from diffuse reflector or mirror 76.
In such a case, the space between fences 68 and 70 is not critical. The converse is true with clear liquid medium 18. Electromagnetic radiation from source 46 is then directed through passages 48 and 50 of elements 22 and 24, or simply directed through passage 82 of fence 70 of embodiment lOB. After interaction with the comaponents in a liquid medium 18, electromagnetic radiation is passed from bag 14 to detector 66 for analysis by a suitable software program in conjuncaion with a personal computer.
Where bag 14 is collapsed by fences 22 and 24, electromagnetic radiation may be passed through bag 14 to obtain a reference reading for use with spectral analyses of liquid in bag 14.
This spectroscopic method and apparatus of the present invention is capable of identifying and measuring many components in a liquid medium 18.
Colorless materials, such as parenteral nutrients have distinctive spectral characteristics in regions outside the visible electromagnetic spectrum (400-700nm). In particular, infrared (3000-25,OOOnm) regions of the electromagnetic spectrum produces distinctive spectral features arising from specific molecular structures that are characteristics of the compounds. Such features derive from molecular vibrations of bonded atoms such as oxygen-hydrogen, carbon-hydrogen, nitrogen-hydrogen, and oxygen-carbon.
Different types o1. carbon-hydrogen bonds can be distinguished, such as those arising from terminal C-H
groups or CH:3 groups, i.e., fundamental molecular vibrations. Similar features occur at multiples of these fundamental frequencies (i.e., shorter wavelengths) and, hence, commonly occurred in the near-infrared. These are referred to as vibrational overtones such as the first and second overtones of carbon-hydrogen near 1700 and 1100 nm, respectively.
Several different fundamental vibrations can combine to form a vibrational absorption at shorter wavelengths called a combination mode, ie., such as oxygen and h.ydrogE~n in molecular water near 1900nm.
Therefore, many regions of the electromagnetic spectrum may be used to obtain useful spectral data.
While in the foregoing, embodiments of the present invention have been set forth in considerable detail for the purposes of making a complete disclosure of the invention, it may be apparent to those of skill in the art that numerous changes may be made in such. detail without departing from the spirit and principles of the invention. Further description of the invention is contained in the following examples.
Th.e following examples are described in detail herein for the purpose of illustration of the present invention, but are not deemed to limit the scope of the invention herein.
The near infrared spectra of several parental nutrient compounds, i.e., water, 70% dextrose injection USP and 10% Travasol amino acid injection was measured individually or in various combinations to illustrate specaral characteristics. Such compounds formed an optically clear solution, which was placed in a fused quartz cuvette having an optical path of one (1) millimeter. The spectral data were acquired with a germanium detector found in a spectrophotometer, Model 200, manufactured by Guided Wave, Inc. of El L)orado Hills, California. Two (2) one meter long, 50U micron core diameter, silica-clad low-OH optical fibers and collimating lenses were connected to the sspectrophotometer. Collimating lenses were placed between one end of each fiber and the cuvette. One fiber transmitted light from the tungsten light source inside the spectrophotometer through collimating lens and cuvette. The second collimating lens received light passing through the cuvette and focused the light into the second fiber, which transmitted the light back to the monochrometer and detector in the spectrophotometer. The absorbance characteristics obtained are charted in Fig. 4. Water reaches a maximum absorbance between 1400 and 1500 nanometers. The remaining components produce additional changes on the long wavelength side of the main water peak in the 1500-1800 nanometer region in Fig. 4.
A polyvinyl chloride bag used for intravenous feeding (IV bag) was filled with sterile water, 70% dextrose injection, USP, and 10% Travasol amino acid injection, which are typical parenteral nutrients. These components formed an optically clear solution. Utilizing the apparatus shown in Fig. 1, spectral data were attained with a germanium detector found in a spectrophotometer distributed by Guided Wave, Inc. under the designation model 200. A pair of one meter long, 500 micron core diameter, silica-clad low-OH optical fiber and collimating lenses were employed with the subject detector. The IV bag was compressed to an optical path of 15 millimeters.
Distinguishing characteristics were uncovered in the compounds within the I.V. bag in the 800 to 1100 nanometer region of an electromagnetic source of radiation. Reference analysis was also performed on an empty I.V. bag. Fig. 5 represents the results of this analysis. EXAMPLE 3 The parenteral compounds of Examples 1 and 2 were placed in an I.V. bag with the addition of a common 20% Intralipid intravenous fat emulsion (I. V.
fat emulsion). The final mixture of nutrients included fat compounds occupying less than 50% of the volume of the I.V. bag mixture. Fig. 6 shows that, in spite of the light. scattering characteristics of the milky solution found in the IV bag containing the fat compounds, transmission may still be performed through 1-2 millimeters of an optical path of the bag. In other words, the bag shown in Fig. 6 represents a squeezing of the bag to a smaller optical path, (1.5 to 2 millimeters) than the optical path represented in Fig. 5. It is estimated that 95% of the light passed through thc~ bag in. this Example was scattered and lost through the first millimeter of the optical path.
Various mixtures o~f 70$ dextrose injection USP, 20%
Intralipid I.V. fat emulsion, 10% Travasol, and water are employed and are identified on Fig. 6. The absorbance characteristics are clearly identifiable for each mixture in which changes in the intensity of the water peak near 1450 nm, effects due to amino acids and dextrose in the 1500-1700 nm region, and contribution from lipid near 1200 nm are identifiable.
As will be shown from diffuse reflectance spectral data hereinafter in Example 4, these features can be used to perform quantitative analysis of the mixtures in the bag.
The apparatus shown in Fig. 3 was employed to conduct diffuse: reflectant/transmittance measurements through I.V. bags constructed of polyvinyl chloride (PVC) filled with mixtures of parenteral nutrients. The mixtures were composed of 20~ Intralipid I.V. fat emulsion, 10% Travasol (amino acid injection solution), 70o dextrose injection solution, and sterile water. Nutrients were measured volumetrically with a graduated cylinder mixed, and placed in one (1) liter PVC I.V. bags. The device depicted in Fig. 3 was set to provide an optical path, excluding the thickness of the I.V. bag material, of about 15 millimeters through the solution in the filled I.V. bag. The set screw spacer means 12, Fig.
1, was employed to compress the bag to this particular optical path setting. Since these mixtures all contained lipid and hence, scattered light suitable for diffuse reflectance measurements, the space set for the optical path was not critical to the measurement. A spectrophotometer was employed, similar to t:he spectrophotometer utilized in Example 1 using an Inc~aAs detector. The source of light was a tungsten lamp. The light was delivered through a 6 mm dia hole in a white Spectralon block available from Labsphere, 7:nc., North Sutton, NH from a 20 watt tungsten source. This block was attached to the stationary fence '70 in Fig. 3. A bundle of 10 individual fibers of the type described in Example 1 were cementE:d into a small metal fitting and inserted through the Spectralon block at 30 degrees to the hole containing t:he tungsten light source. The end of the fiber bundle fitting was coincident with the end of the block in contact with the IV bag. Near infrared spectra werE~ collE~cted between 1100 and 1650 nanometers. Fig. 7 depicts the results obtained where the various mixtures used were clearly recognizable, with the exception of the 75:25 Travasol and lipid mixture, which, generally, is only slightly different from the 75:25 water and lipid mixture.
The spectral differences shown in Fig. 7 can be quantified with the commonly used method of Principal Component Analysis (PCA). PCA is essentially a pattern recognition procedure that can assign one number to the entire spectrum employed in the analysis,. PCA is accomplished by analyzing all spectral data of all samples in determining the linear combination of data that explains the largest variation of spectral information. A different linear combination is ne};t determined that shows the next largest variation in the spectral data. The linear combinations: are determined in this way. Each linear combination is referred to as a FACTOR which provides co-efficient: that multiply the data at each wavelength. The product of this multiplication is summed to dsaermine one number which is referred to as a SCORE. Thus, by plotting SCORES from FACTOR I
against those from FACTOR II, samples can be distinguished or identified. In mathematical terms, FACTORS are a set of orthogonal eigenvectors whose lengths represent the percentage of variation in spectral data. SCORES are obtained by multiplying the elements of each e~igenvector, referred to as a LOADING
(each of which is a co-efficient for the spectral data at a specific wavelength) times the absorbance at that wavelength, and summing the results. Essentially, each sample is projected on each eigenvector and the distance from the origin i.e., the intersection of all eigenvector~; is thus measured. Other mathematical methods exi~,t for the purposes of identification of data, includling the computation of direction cosines, factor analysis, and cluster analysis. Referring to Fig. 8, a PC'A plot is illustrated using SCORES from the first two FACTORS of the diffuse reflectance data from the samples presented in Fig. 7. Table 1 herein represents the volume fraction of the nutrients employed in the preparation of Fig. 8:
TABLE I
10% STERILE 70% 20%
SAMPLE _TRAVASOL WATER DEXTROSE INTRALIPID
1 0.50 0.50 2 0. 50 0. 50 3 0.50 0.50 4 0.85 0.15 5 O.B5 0.15 6 0.85 0.15 7 0.75 0.25 8 0.75 0.25 9 0.'75 0.25 10 0.'75 0.25 11 0.75 0.25 12 0.75 0.25 13 0..25 0.25 0.25 0.25 14 0..25 0.25 0.25 0.25 These two f,~ctors account for 970 of the spectral variation among all of the samples, each identified by a sample nw:nber with a circle around the same. The 70% dextrose injection USP, water, and l0% Travasol amino acid injection components are clearly distinguished by the solid lines of Fig. 8. The 20%
intralipid fat emulsion content is also clearly shown by the three dashed lines representing 15%, 25%, and 50% intrali~~id. The solid Travasol and water lines lie closer to one another, but are significantly spaced from the dextrose line in Fig. 8. Such a relationship corresponds to spectral data in which water and T:ravasol are more similar to each other than dextrose. repeated measurements on the same IV bag showed reasonable reproductibility, i.e., samples 7 and 8 and s~~mples 11 and 12 of Fig. 8.
P~~rtial-Least Squares (PLS) method was also employed in the diffuse reflectance method for the samples shown in Fig. 8. The results of this method are shown in Figs. 9-10 of the present invention.
Partial-Least Squares (PLS) multivariate procedure is commonly used to determine chemical or physical property information from spectral data. Computer programs such as L1NSCRAMBLER are available from Camo of Norway. SPECTRACALC, and GRAMS/386 are available from Galactic Industries, Inc., of Salem, New Hampshire. Pirouette is available from Infometrics of Redmond, Wa~.hington. GRAMS/386 was used in the present analysis with a personal computer. PLS
incorporate~~ the benefits of PCA and attempts to provide a model of. the data with as few a number of FACTORS as is needed. A six FACTOR PLS model of the diffuse reflectance data of Table I represents a strong indication that mixtures in IV bags can be analyzed nom-invasively. Figs. 9 and 10 show predictions of 70°-<> dextrose injection and 20%
intralipid IV fat emulsion.
PL~S ana7.ysis of the one millimeter optical path using transmission through cuvettes, shown in Fig. 4 for samples without fat emulsion, also produced excellent quantitative results. The prediction for 70% dextrose injecaion USP in the mixture from a five FACTOR PLS model as presented in Fig. 11. The standard error of calibration for the sample set was 5%. The PLS, model in Fig. 11 utilized all spectral information from all samples as seen in Fig. 4.
Since it is often desirable to use a simple system comprising only a few wave lengths for quantitative analysis, a multi linear Regression Method (MLR) can also be used to predict physical properties of liquids and solids and analyze mixtures from near infrared spectra. MLR was performed on the one millimeter transmission spectra shown in Fig. 4.
The result :in calibration are presented in Figs. 12, 13, and 14, for 70~ dextrose injection USP, sterile water, and :LOS Travasol amino acid injection, respectivel~~. The data were generated by employing 2, 3, and 5 wa~~elengths between 1100 and 1800 nanometers, respectivel~t. This data are shown in Table 2 as follows:
TABLE II
70°~ DEXTRO:iE WATER 10% TRAVASOL
SAMPLE ACT._ PRED. ACT. PRED. ACT. PRED.
1 0.000 0.007 0.000 0.014 1.000 1.003 2 0.000 -0.005 1.000 0.977 0.000 0.072 3 1.000 0.986 0.000 -0.041 0.000 -0.061 4 0.000 0.008 0.500 0.468 0.500 0.475 5 0.500 0.522 0.500 0.517 0.000 -0.063 6 0.500 0.489 0.000 0.038 0.500 0.524 7 0.333 0.344 0.333 0.310 0.333 0.307 8 0.6fi7 0.681 0.166 0.128 0.166 0.241 9 0.1(>6 0.156 0.166 0.198 0.667 0.675 10 0.1(>6 0.162 0.667 0.653 0.167 0.149 11 0.700 0.697 0.300 0.306 0.000 0.052 12 0.2~i0 0.240 0.500 0.488 0.250 0.219 13 0.300 0.308 0.700 0.747 0.000 0.057 14 0.400 0.399 0.200 0.209 0.400 0.352 15 0.000 -0.007 0.300 0.320 0.700 0.683 Wavelen _c~th nm c:oeff. Waveln. Waveln. Coeff.
Coeff.
156 6 L6.21 1528 3.5355 1533 -51.3572 1716 --5.374:1 1716 -104.7859 1778 56.0781 Offset --4.9432 1744 98.6863 1287 194.9018 Mult. 0.99378 Offs et -3.4804 1193 668.3302 R -SEC 0.0347 Mult . R 0.99521 1194 455.3483 SEC 0.0306 Offset 9.8891 Mult.R 0.98888 SEC 0.0548 As may be observed, lengths of wave 1566 and nanomet ers were for dextrose. The employed wavelengths water and employed Travasol for are also indicated he indication is thata on TablE~
2. T
simpler and less ve system ng several expensi havi discrete dei:.ectors, each covered by a narrow wavelength :Filter or a device having means to switch between several discrete wavelengths, could be built to quantitai=ively predict the composition of mixtures as these shown in Fig. 4.
A stepwise multiple linear regression program was also 'used to determine a small set of wavelengths which could be used to predict the intralipid <ind 70% dextrose mixture in IV bags filled with the samples identified in Table II, analyzed by the embodiment of l0A of Fig. 1 (transmittance). The optical path was set to a distance of approximately 1.6 mm. Aci:ual versus predicted values were plotted as shown on Fig. 15. It should be noted that a perfect calibration would plot on the diagonal l~.ne found in Fic~. 15. Three (3) and five (5) wavelengths were used to produce excellent fits with standard errors of pi~ediction of 2.1 and 3.7% for the 20%
intralipid component and the 70% dextrose component in the mixture,, respectively. The three (3) wavelengths used for thc: 20% intralipid were 1606, 1536, and 1532 nanometers which .are listed in decreasing order of importance. Similarly, the five (5) lengths employed for the 70% dextrose were 1414, 1610, 1212, 1424, and 1200 nanomei~ers, also listed in order of importance.
Each mathem<~tical solution also included a constant term.
Claims (21)
- WHAT IS CLAIMED IS:
An apparatus for measuring a component in a liquid medium within the chamber of a flexible translucent container formed by a wall portion, comprising:
a. spacer means for sequentially determining a plurality of optical paths across the container wall portion and chamber, and the bag wall portion alone said spacer means including a passage for electromagnetic radiation; and b. a source of electromagnetic radiation capable of directing electromagnetic radiation through said passage, through the wall portion of the container, and along any of said determined optical paths, said source of electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and c. detector means for analyzing said electromagnetic radiation after interaction with the components in the bag chamber and the wall portion of the bag. - 2. The apparatus of claim 1 in which said spacer means includes a pair of elements placed in opposition to one another, at least one of said elements including a passage for electromagnetic radiation to the wall portion of the bag.
- 3. The apparatus of claim 2 wherein said apparatus additionally comprises adjustment means for establishing the distance between said pair of elements.
- 4. The apparatus of claim 3 in which said adjustment means includes a threaded member spanning said pair of elements, said threaded member threadingly engaging one of said elements to effect movement of said one of said elements thereby, and a guide for confining movement of said one of said elements to a predefined direction.
- 5. The apparatus of claim 4 in which said guide includes a pair of elongated elements extending between said pair of elements.
- 6. The apparatus of claim 1 which additionally includes a fiber optic conduit for transporting electromagnetic radiation from said source of electromagnetic radiation to said spacer means passage.
- 7. The apparatus of claim 1 which additionally includes a fiber optical conduit for transporting electromagnetic radiation from said spacer means to said detector means.
- 8. The apparatus of claim 2 which additionally comprises a reflector located at one of said pair of elements, said reflector being located to reflect electromagnetic radiation, passed through the chamber of the flexible translucent bag back through the chamber of the flexible translucent bag.
- 9. The apparatus of claim 1 in which said source of electromagnetic radiation emanates electromagnetic radiation in the near-infrared region of the electromagnetic spectrum.
- 10. The apparatus of claim 1 which additionally includes at least one wavelength filter placed between said source of electromagnetic radiation and said detector means.
- 11. The apparatus of claim 10 which additionally includes a lens placed between said source of electromagnetic radiation and said detector means.
- 12. A method of analyzing components in a liquid medium within the chamber of a flexible bag comprising the steps of:
a. placing the bag in spacer means for determining the optical path across the bag chamber, said spacer means including a passage for electromagnetic radiation;
b. directing electromagnetic radiation from a source of electromagnetic radiation to the components in said bag chamber for interaction therewith; and c. analyzing said electromagnetic radiation with detector means after interaction of said electromagnetic radiation with the components in the bag chamber. - 13. The method of claim 12 in which said step of analyzing said electromagnetic radiation further includes the step of analyzing electromagnetic radiation transmitted through said components in the bag chamber.
- 14. The method of claim 12 in which said step of analyzing said electromagnetic radiation further includes the step of analyzing electromagnetic radiation reflected from said components in the flexible bag.
- 15. The method of claim 12 in which said step of analyzing said electromagnetic radiation further includes the step of analyzing electromagnetic radiation transmitted through and reflected back through components in the bag chamber.
- 16. The method of claim 12 wherein electromagnetic radiation is passed through the flexible bag alone in order to obtain a reference spectrum.
- 17. The method of claim 16 which further comprises the step of expelling the liquid medium from the flexible bag prior to said step of passing electromagnetic radiation through the flexible bag alone.
- 18. The method of claim 16 in which said optical path is a first optical path and said method further comprises the steps of d) placing the bag in said spacer means for determining a second optical path across the bag chamber; .e) directing electromagnetic radiation to the components in said chamber for interaction therewith;
and f) analyzing said electromagnetic radiation with said detector means after interaction of said electromagnetic radiation with the components in the bag chamber. - 19. The method of analyzing components in a liquid medium within the chamber of a flexible bag according to claim 12 wherein said components are parenteral and enteral nutrients.
- 20. An apparatus for detecting light scattering components in a liquid medium within the chamber of a flexible translucent bag formed by a wall portion, comprising:
a. a fence element, said fence element including a passage for electromagnetic radiation to the wall portion of the bag;
b. a source of electromagnetic radiation capable of directing electromagnetic radiation through said fence element passage, said source of electromagnetic radiation being capable of interaction with a component in the bag chamber and the wall portion of the bag; and c. detector means for analyzing said electromagnetic radiation after interaction with the components in the bag chamber and the wall portion of the bag, said detector means receiving said electromagnetic radiation, after interaction with a component in the bag chamber, through said fence passage. - 21. An apparatus for non-invasively identifying components in a liquid medium within an interior of a flexible bag, the apparatus comprising:
a source of electromagnetic radiation capable of directing electromagnetic radiation into the interior of the flexible bag, the source of electromagnetic radiation capable of interaction with the components in the flexible bag interior and the flexible bag;
optical detector means located outside the flexible bag receiving the electromagnetic radiation after interaction with the components in the flexible bag interior and the wall portion of the flexible bag and providing a signal indicative thereof; and means for analyzing the signal to identify the components of the liquid medium in the flexible bag.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/317,114 US5510621A (en) | 1994-10-03 | 1994-10-03 | Apparatus and method for measuring components in a bag |
| US08/317,114 | 1994-10-03 |
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| CA2159235A1 CA2159235A1 (en) | 1996-04-04 |
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| CA002159235A Expired - Fee Related CA2159235C (en) | 1994-10-03 | 1995-09-27 | Apparatus and method for measuring components in a bag |
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| US (2) | US5510621A (en) |
| EP (1) | EP0706043B1 (en) |
| JP (1) | JPH08210973A (en) |
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| US6584805B1 (en) | 1993-08-24 | 2003-07-01 | Coors Brewing Company | Hot bottle inspection apparatus |
| US6025910A (en) * | 1995-09-12 | 2000-02-15 | Coors Brewing Company | Object inspection method utilizing a corrected image to find unknown characteristic |
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- 1995-10-02 DE DE69516620T patent/DE69516620T2/en not_active Expired - Lifetime
- 1995-10-02 EP EP95306954A patent/EP0706043B1/en not_active Expired - Lifetime
- 1995-10-02 AT AT95306954T patent/ATE192572T1/en not_active IP Right Cessation
- 1995-10-03 AU AU33040/95A patent/AU693926B2/en not_active Expired
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| AU3304095A (en) | 1996-04-18 |
| JPH08210973A (en) | 1996-08-20 |
| ATE192572T1 (en) | 2000-05-15 |
| CA2159235A1 (en) | 1996-04-04 |
| EP0706043B1 (en) | 2000-05-03 |
| EP0706043A3 (en) | 1998-05-20 |
| AU693926B2 (en) | 1998-07-09 |
| DE69516620T2 (en) | 2001-01-11 |
| EP0706043A2 (en) | 1996-04-10 |
| US5510621A (en) | 1996-04-23 |
| US5750998A (en) | 1998-05-12 |
| DE69516620D1 (en) | 2000-06-08 |
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