LAGESSON HANS VERNER (SE)
OLSSON LENNART (SE)
LAGESSON HANS VERNER (SE)
| FR2873812A1 | 2006-02-03 | |||
| US20060260419A1 | 2006-11-23 |
KOZIEL J A ET AL: "System for the generation of standard gas mixtures of volatile and semi-volatile organic compounds for calibrations of solid-phase microextraction and other sampling devices", JOURNAL OF CHROMATOGRAPHY, ELSEVIER SCIENCE PUBLISHERS B.V, NL, vol. 1025, no. 1, 30 January 2004 (2004-01-30), pages 3 - 9, XP004480714, ISSN: 0021-9673, DOI: 10.1016/J.CHROMA.2003.10.079
CHEN Y ET AL: "CALIBRATION FOR ON-SITE ANALYSIS OF HYDROCARBONS IN AQUEOUS AND GASEOUS SAMPLES USING SOLID-PHASE MICROEXTRACTION", ANALYTICAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 75, no. 23, 1 December 2003 (2003-12-01), pages 6485 - 6493, XP001047348, ISSN: 0003-2700, DOI: 10.1021/AC0349328
| CLAIMS 1 . An apparatus for collecting and trapping compounds on to at least one solid phase micro extraction (SPME) fibre, characterized in that means are provided for creating a dynamic sample air flow along with the fibre in a narrow bore tubing and that at least one inlet of sample air is connected to said tubing. 2. An apparatus as claimed in claim 1 , further comprising a T formed tubing construction having a first opening for insertion of said SPME fibre, a second opening for the inlet of the exhaled breath air flow, and a third opening connected to a variable air flow pump. 3. An apparatus as claimed in claim 2, wherein said SPME fibre is supported in a needle, said first opening of said T-formed tubing construction being sealed by a septum for the penetration of the SPME needle. 4. An apparatus as claimed in claim 2, wherein said pump is designed to draw a flow of 1 - 500 ml/min giving an air flow rate along with the fibre of 1 - 100 cm/sec and where the high flow rate passing by the fibre ensures an effective shortening of the diffusion boundary around the fibre. 5. An apparatus as claimed in any of the preceding claims, comprising an arrangement operable in a first mode A in which a temporary hold up compartment is connected to said narrow bore tubing, said temporary hold up compartment having a first inlet for sample air, and a second mode B in which a second inlet for sample air is connected to said narrow bore tubing. 6. An apparatus as claimed in claim 5, wherein said temporary hold up compartment comprises a cylinder having a diameter of 2 - 30 mm and a length of 10 - 300 mm formed by metal, glass, ceramic or plastic that is internally Al coated or silanized in order to minimize losses due to adsorption at or diffusion into the walls of the compartment, said cylinder being designed to keep the sample air at an elevated temperature in order to prevent condensation of the water vapour from the exhaled breath. 7. An apparatus as claimed in claim 5 or claim 6, wherein a three-way valve is connected to said narrow bore tubing, said first inlet and said second inlet, so as to connect said narrow bore tubing to said first inlet in mode A and to said second inlet in mode B. 8. A method for collecting and trapping compounds on to a solid phase micro extraction (SPME) fibre, characterized by creating and directing a dynamic sample air flow along with the fibre in a narrow bore tubing and supplying sample air to said tubing through at least one inlet. 9. A method as claimed in claim 8, also comprising exposing said fibre to a flow of 1 -500 ml/min corresponding to an air flow rate along said fibre of 1 -100 cm/s and resulting in an effective shortening of diffusion boundary around said fibre. 10. A method as claimed in claim 8 or claim 9, also comprising connecting in a first mode A a temporary hold up compartment having a first inlet for sample air to said narrow bore tubing, and in a second mode B a second inlet for sample air to said narrow bore tubing. 1 1 . A method as claimed in any of claim 8-10, also comprising creating a dynamic sample air flow perpendicular to said at least one SPME fibre. 12. A method as claimed in claim 1 1 , also comprising creating a turbulent dynamic sample air flow perpendicular to said at least one SPME fibre. |
COLLECTION OF COMPOUNDS AND GASES ON TO A SUITABLE
ADSORBENT DEVICE. TECHNICAL FIELD
The present invention concerns air sampling and collection of volatile compounds and gases at low concentrations in exhaled breath and other gases. The compounds found in exhaled breath are used as biomarkers of diseases like lung cancer, asthma and diabetes. The presence of compounds in exhaled breath can also be used for evaluation of for example
environmental exposure, drug of abuse and medical treatments.
BACKGROUND ART
The basic technology is known and usually involves exhaled breath collected in a Tedlar or Mylar bag or a plastic or glass cylinder. A solid phase micro extraction (SPME) fiber is inserted, through a septum, into the Tedlar bag or glass bottle for at least 30 min and typically several hours at room temperature to extract the volatile compounds (VOC ' s). SPME is an attractive solvent free alternative, which combines sampling and pre concentration in one step. The SPME technology is also inexpensive and has high time efficiency and is used for both air and liquids. The drawbacks for a conventional static air sampling are long sampling time, low recovery and unsatisfied reproducibility.
SUMMARY OF THE INVENTION
The object of the present invention is to eliminate the drawbacks mentioned above. The invention relates to physical, mechanical and software control solutions. The invention solves major problems and shortcomings with present technology, is very versatile and can be used for various applications. One particular use is for detection of metabolic or other substances emanating from living cells, tissues and in particular that can be found in exhaled air, saliva, sweat, blood and urine from humans, animals, organisms and plants etc. for detection of various deceases and metabolic activities like stress. Substances can be such as nitrogen oxide, urea, acetone, isoprene, carbon disulfide coming from diseases like cancer, gastric ulcers, asthma, diabetes, psychiatric disorders, drug abuse, stress conditions and intoxications, etc.
Contrary to the static collection of compounds on to the SPME fibre as disclosed in prior art the present invention is based on a dynamic collection from a constant exhaled air flow. This implies that the exhaled breath air is passing the adsorption fibre at a relatively high speed. In this mode the thickness of the static boundary air layer surrounding the SPME fibre is reduced and the sorption rate is considerably increased. This in turn gives a considerably shorter sampling time, a much higher recovery and better reproducibility. One or a plurality of SPME fibres can be used.
Exhaled breath is, by nature, a pulsating flow. Moreover there is a need for analysing mixed expiratory air as well as exhaled air consisting mainly of the alveolar portion of the air. The alveolar air is pushed out actively by the test subject. There are a number of situations where the test subject cannot participate actively in the sampling procedure. Examples of such situations are exhaled breath sampling from newborn children in an incubator and persons treated with intensive care. The present invention solves these situation in an effective and yet simple way.
The biomarkers for various diseases are most often present in the exhaled breath at very low concentrations. This situation implies that risks for adsorption on and diffusion into materials in contact with the exhaled breath sample must be minimized. This is taken into consideration in the present invention. The chemical analysis of the compounds trapped on to the SPME fibre are preferably carried out by gas chromatography hyphenated with ultraviolet light absorption (GC-UV) but the method of analysis could also be gas chromatography linked to mass spectroscopy (GC-MS) or any other method of analyze.
According to a first aspect of the invention a dynamic sample air flow of the exhaled breath is created along with the SPME fibre. A suitable, relatively high flow rate is obtained by leading the air through a narrow bore glass tubing surrounding the SPME fibre. In a comparison with a static air sampling device like inside a sampling bag the inventione gives a considerably faster sampling rate, a considerably improved recovery and a considerably better
reproducibility.
According to a second aspect of the invention the flow arrangement comprises a T formed glass tubing construction. A first opening has a septum for the penetration of the SPME needle. A second opening is for the inlet of the exhaled breath air flow. A third opening is connected to a pump which can draw a variable air flow of 1 - 100 ml/min giving an air flow rate along with the fibre of 1 - 100 cm/sec.
According to a third aspect of the invention there are two modes of exhaled breath sampling. For the first mode (A) there is a requirement that the test person is able to participate actively in the sampling procedure. The second mode (B) implies that the mixed exhaled breath is drawn directly to the adsorbent layer of the fibre. In this mode there is no need for the test person to participate actively in the sampling process. According to a fourth aspect of invention there is a temporary exhaled breath air compartment consisting of preferably a cylinder 20 - 30 mm in diameter and 200 - 300 mm long. The glass or plastic cylinder is internally Al coated or silanized in order to minimize losses due to adsorption or diffusion into the walls of the compartment. The exhaled breath compartment has an inlet for the exhaled breath coming from the test person and an outlet going to a three way valve which in turn is leading to the inlet for the exposure to the SPME fibre. In the A inlet mode the three way valve is open to the compartment and in the B mode the three way valve is open for the B mode flow.
According to a fifth aspect of invention it can be used in any sampling of unidentified gas and/or mixed gases that have to be identified and quantified.
BRIEF DESCRIPTION OF THE DRAWINGS
In order to explain the invention, a number of embodiments of the invention will be described below with reference to the drawings, in which: Fig. 1 shows the direction of sample air along with the SPME fibre. Fig. 2 shows the flow arrangement in the T shaped glass tubing device comprising (1 ) Inlet of air sample flow (2) septum for SPME needle insertion (3) SPME needle (4) coated adsorption fibre (5) outlet leading to a pump able to giving variable flow rates. Fig. 3 shows the whole set up of the exhaled breath sampling device with the mode A and mode B combined exhaled breath inlets in one unit.
Same reference numerals have been used to indicate the same parts in the figures to increase the readability of the description and for the sake of clarity. The figures are not made to scale, and the relative dimensions of the illustrated objects may be disproportional.
Fig. 4 shows a cross section of gas flow perpendicular to the SPME coated adsorption fibre (5) and with gas flow (9)
DETAILED DESCRIPTION
The invention relates to a method of considerable improvement of the versatility, speed, recovery and reproducibility for sampling of volatile compounds and gases in exhaled breath. For the sampling the SPME technology is employed whereby the compounds of interest are trapped and adsorbed on a SPME fibre with various coatings treatments on the fibre. In various embodiments a plurality of fibres are used. Different fibres can be used in parallel for improved simultaneous or sequential adsorbtion. Contrary to the static sampling of conventional exhaled breath air sampling the present invention uses a dynamic constant flow air sampling. The optimum air flow rate depends to some extent on the volatility of the compounds to be determined. The qualitative and quantitative analysis of the compounds adsorbed on the SPME fibre are preferably analysed with gas chromatography hyphenated with UV spectrophotometry (GC-UV) but gas chromatography hyphenated with mass spectroscopy or other detector principles can also be used.
Fig. 1 shows the direction of exhaled breath air flow along with the SPME fibre. Fig. 2 shows the exhaled breath air flow arrangement within a T shaped glass device with internal diameter of 1 - 2 mm. The narrow diameter of the tubing has the function of giving a high air flow speed at relatively low flow rates. The exhaled air flow inlet is at (1 ) and the septum (2) serves as a gas tight device for the insertion of the SPME needle (3). The position of the SPME fibre (4) is in the part of the T as shown by the figure. The creation of the flow is made by a pump (not shown) connected at (5) and drawing the air sample through the system at preset various constant air flows. The pump is preferably battery driven.
Fig. 3 shows the whole combined invention device comprising the flow arrangement shown in Fig. 2 and a temporary hold (6) for up for exhaled breath air. This compartment consists of a tubing 20 - 30 mm in diameter and having a length of 200 - 300 mm. It has a wall thickness of 1 - 2 mm and is preferably made of a plastic or glass material. In order to minimize losses of compound, due to adsorption and diffusion, present in the air sample, the inner part of the wall has an Al coating or a silanized preventive layer.
Preferably the temporary hold up cylinder is thermally isolated to some extent in order to minimize condensation of the water vapour content in the exhaled breath.
In the A mode of sampling the air inlet occurs as shown and the outlet is at (8). The temporary hold up compartment is in connection with a three way valve (7) and at the A mode air sampling the air is drawn up to the SPME fibre by means of a pump. A compartement (6) for temporary exhaled breath air is connected to the three way valve (7). Exhaled breath waste may exit at the outlet (8).
In the B mode sampling the valve position is turned 90 ° counter clockwise and the sampling air is drawn directly from the position of sampling (B mode inlet) up to the SPME fibre.
Fig. 4 shows a cross section of gas flow perpendicular to the SPME coated adsorption fibre (5) and with gas flow (9)