Measuring and testing – With fluid pressure – Porosity or permeability
Reexamination Certificate
1999-11-24
2002-03-26
Williams, Hezron (Department: 2856)
Measuring and testing
With fluid pressure
Porosity or permeability
C073S064470
Reexamination Certificate
active
06360588
ABSTRACT:
BACKGROUND OF THE INVENTION
The subject invention relates to the study of the transport of substances through barriers or membranes. In a specific example, the materials and methods of the subject invention can be used to study the transport of substances through skin.
Prior techniques for studying the transport properties of various substances through skin are expensive, labor intensive, and fail to yield time-dependent transport data. One such technique includes exposing mice to a substance under study and then analyzing the urine, blood, or actual skin tissue of the mice. In contrast, the subject technology is less expensive, less labor intensive, and yields time-dependent transport data.
At present, both in vivo and in vitro animal studies are employed to evaluate transdermal penetration characteristics of chemicals. The in vivo studies involve restraining an animal so that the material can be placed on it and insure that the substance will not be licked off or evaporate. The animal must then be housed, and urine or other biological samples collected. Typically, the animal is killed and the distribution of the applied material determined by, for example, extraction of animal parts. In vitro studies are somewhat simpler. The animal's skin is removed from the animal and placed in a diffusion cell where it is suspended on top of a liquid, one or more chemicals are placed on the skin and subsequently diffuses through the skin into the liquid. This liquid is then analyzed for the applied compound(s).
In conventional membrane introduction mass spectrometry (MIMS), samples are introduced into a mass spectrometer through a probe having a membrane across its tip. The probe is then inserted into the ion source portion of the mass spectrometer. A mesh support can be placed on the mass spectrometer side of the membrane to hold the membrane in place when the probe is inserted into the ion source, which is under vacuum. This membrane is typically made of silicone, and serves to control the introduction of the substance under study into a mass spectrometer. Typically, the focus is not on the membrane, or the interaction of the substance. Rather, MIMS is generally concerned with determining the constituents of a substance in a liquid form. In order to volatilize the sample and mobile phase, the source is usually run at temperatures exceeding 200° C. Mobile phase is pumped over the membrane allowing the analyte to diffuse through the membrane into the MS source. Once in the MS source, the analyte breaks apart to give characteristic fragments, identifying the constituents of the analyte. A major portion of the mobile phase that passes through the membrane is removed by the vacuum pumping system. In addition, the mass spectrometer can be adjusted so that it will not “see” the remaining mobile phase ions. This technique is adequate when one wishes to identify components in a liquid. Both the vacuum and the temperature of the source can, however, drastically alter the permeability characteristics of a membrane.
Accordingly, a method and device which would allow diffusion across the membrane to occur at ambient conditions would be beneficial.
BRIEF SUMMARY OF THE INVENTION
The subject invention provides unique instrumentation and methods useful in the quantitative and qualitative evaluation of the transport of compounds across a membrane. In a specific embodiment, the subject invention pertains to the use of a membrane atmospheric pressure interface (MAPI) to investigate the penetration/permeation and transport of substances across materials. In a preferred embodiment, the movement of materials through skin are analyzed in a time-dependent manner with great accuracy.
In contrast to membrane introduction mass spectrometry (MIMS), MAPI can allow one to expose a first side of fabric, skin membrane, or other material to a substance and study the amount per time of the substance which exits the other side of the skin, fabric, or other material. Analysis of this time-dependent data can allow one to determine the transport properties of the known substance through that membrane. A further aspect of the subject invention is the ability to determine if an analyte is degraded or otherwise modified as it interacts with, or passes through the membrane.
The subject technology can utilize human, animal, artificial, and/or synthetic skin, and is particularly advantageous for kinetics studies and synergistic effects studies involving the dependence of the transport properties of one substance on the presence of another substance. Similarly, the subject technology can be used to evaluate the permeation rate, breakthrough time and normalized breakthrough time of substance(s) through materials used for chemical protective clothing.
Although mass spectrometry is specifically exemplified herein as a preferred means for detecting analytes passing through the membrane, other forms of detection including, for example, gas chromatography, high performance liquid chromatography, and biological assay, can all be used for detecting compounds which have passed through the skin membrane.
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ASTM D 3985 -81.
Couch Margaret Wheland
Griffin Timothy Patrick
Ross Edward Allan
Schmidt Charles J.
Tebbett Ian R.
Politzer Jay
Saliwanchik Lloyd & Saliwanchik
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