Stock material or miscellaneous articles – Web or sheet containing structurally defined element or... – Composite having voids in a component
Reexamination Certificate
1999-03-31
2001-10-23
Kopec, Mark (Department: 1751)
Stock material or miscellaneous articles
Web or sheet containing structurally defined element or...
Composite having voids in a component
C428S305500, C428S306600, C428S314400, C428S316600, C428S319100, C428S320200, C428S322700, C424S422000, C424S423000, C424S424000, C435S177000, C435S180000
Reexamination Certificate
active
06306491
ABSTRACT:
FIELD OF THE INVENTION
This invention generally relates to materials that assist respiration of living cells contained in a cell-containing device. More particularly, the invention relates to materials within which gases are easily acquired, conducted, and/or delivered from a site of higher partial gas pressure to a site of lower partial gas pressure in support of living cells.
BACKGROUND
All biological entities undergoing metabolism consume nutrients and produce waste products to maintain their metabolic processes. Biological entities include organelles, cells, tissues, organs, and organisms. In most instances, exchange of nutrients and waste products occurs continuously between biological entities and an external environment of the entities. For most biological systems, exchange of nutrients and wastes takes place through a particular aqueous medium, such as cytoplasm, intercellular fluid, plasma, lymph, cell-culture media, fresh water, seawater, or blood. Exchange of nutrients and wastes also takes place across structural forms, such as intra-cellular membranes, cell membranes, cell walls, extra-cellular matrix material, alveoli, and capillaries. The rate of exchange of nutrients and wastes is influenced by the particular type of biological entity, the degree of activity of the entity, the composition of the aqueous media and structural forms, as well as the composition of the nutrient or waste material. The nutrients and waste products of most interest with respect to the present invention are the respiratory gases oxygen and carbon dioxide. Exchange of these gases between a metabolically active site of a biological entity and an external environment of the entity is referred to herein as respiration. Respiration of gaseous mass occurs through diffusional means and convective means. The rate of respiration of a particular biological entity is related to the rate of metabolism of the entity.
Metabolism is “the sum of all the physical and chemical processes by which living organized substance is produced and maintained, and also the transformation by which energy is made available for the uses of an organism” (
Dorland's Illustrated Medical Dictionary,
27
th
Edition, 1988). In the aerobic metabolism of most human cells, for example, oxygen is consumed and carbon dioxide is produced during generation of such high-energy molecules as adenosine 5′-triphosphate (ATP) by catabolism of the nutrient glucose and other metabolic fuels. In this and other metabolic processes, a localized imbalance of nutrients and wastes occurs with respect to the biological entity and an external environment of the entity. If allowed to persist or increase beyond a certain point, the imbalance leads to a life-threatening buildup of wastes or depletion of nutrients. Metabolic processes can be maintained only if nutrients and wastes are exchanged in an appropriate amount and at an appropriate rate.
Diffusion is a means by which gaseous mass is exchanged between a metabolically active site and an external environmental site. Diffusion is driven by a difference in partial as pressure between the sites. As metabolism depletes oxygen at a metabolically active site, for example, a localized “oxygen sink” is established. If an external environment of the biological entity has oxygen at a higher partial gas pressure than the metabolically active site, oxygen is transferred to the metabolically active site through various media and structures by diffusion. Gaseous wastes, such as carbon dioxide, diffuse according to the same process, but in the opposite direction. Diffusion is most effective in biological entities over small distances ranging from inter-molecular distances to a few millimeters.
In discussing animal physiology, Schmidt-Nielsen, (
Animal Physiology: Adaptation and Environment
, Cambridge University Press, 4
th
Edition, pages 16-17 (1990)) employed the following equation developed by E. Newton Harvey (1928) to illustrate that dependence on diffusion alone places distinct limitations on the maximum size to which a population of cells or an organism can grow. This in turn gives an indication of the distances over which diffusion through aqueous media can effectively operate in biological systems as a means of respiratory gas exchange.
F
O
2
=
V
O
2
r
2
6
K
In the equation, F
02
represents the concentration of oxygen at the surface of a spherical organism, expressed in fractions of an atmosphere; V
02
represents the rate of oxygen consumption by the organism as cubic centimeters of oxygen per cubic centimeter of tissue per minute; r is the radius of the spherical cell or organism in centimeters; and K is the diffusion constant in square centimeters per atmosphere of oxygen that will diffuse per minute through an area of one square centimeter when the gradient is one atmosphere per centimeter.
When numbers are used in the equation for a hypothetical organism having a spherical shape and a radius of one centimeter, with an oxygen consumption of 0.001 milliliters per gram oxygen per minute, and a diffusion constant of 11×10
−6
per square centimeter per atmosphere per minute (Ibid.), it is found that the concentration of oxygen at the surface, necessary to supply the entire organism by diffusion alone, is fifteen atmospheres. Since the partial pressure of oxygen in the earth's atmosphere and upper levels of the oceans is about 0.21 atmospheres, an organism of this type is too large to exist using diffusion alone. For a more realistic organism having a radius of about one millimeter, the required oxygen concentration at the surface of the organism is 0.15 atmospheres. Well-aerated water at sea level contains about 0.21 atmospheres of oxygen. Accordingly, an organism with a radius on the order of one millimeter could survive on aqueously dissolved oxygen by diffusion alone. Generally, the reliance of these organisms on diffusion through aqueous media to exchange dissolved respiratory gases places a size limit on the organisms of about a one millimeter radius. Viewed another way, diffusion-based exchange of respiratory gases through aqueous media can support the metabolic activity of this hypothetical biological entity only if the diffusion distances required for the exchange of the respiratory gases do not exceed about one millimeter in length. This maximum distance for diffusion-based exchange of respiratory gases between a biological entity and an external environment defines a “diffusion-delimited boundary.”
Respiratory gas exchange within a diffusion-delimited boundary is referred to herein as occurring within an “internal respiratory system.” Examples of biological entities that function within an internal respiratory system include mitochondria, chloroplasts, individual cells, single-celled organisms, small multi-cellular organisms, collections of small numbers of cells, and specific anatomic regions of certain aquatic organisms, such as jellyfish. Depending on their actual size and metabolic requirements, the cell walls, cell membranes, or the edges of the cell masses usually represent the diffusion-delimited boundary of these biological entities. These entities survive within a diffusion-delimited boundary because diffusion-based exchange of respiratory gas occurs over distances that are effective in transferring respiratory gases in sufficient amounts and at sufficient rates to support the metabolic activities of the entities.
In many cases, the diffusion-based process of the internal respiratory system may be supplemented by convection-based processes beyond the diffusion-delimited boundary. Respiratory gas exchange beyond a diffusion-delimited boundary is referred to herein as occurring in an “external respiratory system.” Gas exchange in external respiratory systems occurs with the aid of convection-based means. Examples of convection-based external respiratory systems include animal vascular systems and pulmonary systems of both aquatic and terrestrial organisms. External respiratory systems are characterized by well defined anatomical
Bain James R.
Kram Brian H.
Mish Stanley L.
Muehlbauer Michael J.
Boyer Charles
Gore Enterprise Holdings Inc.
Kopec Mark
Sheets Eric J
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