Physiological saline solution and its method of manufacture and use

Abstract

Physiological saline solution (PSS) for in vitro fetal medicine and methods of its manufacture and use are disclosed. In one embodiment, disclosed herein is a PSS having the following: an aqueous solvent: about 1.0 mM to about 2.0 mM calcium chloride; about 3.0 mM to about 5.0 mM potassium chloride; about 15.0 mM to about 20 mM sodium bicarbonate; about 90 mM to about 110 mM sodium chloride; and about 9 mM to about 13 mM sodium acetate, the solution having a pH ranging from about 7.0 to about 7.4 and an osmolality ranging from about 250 mOsm to about 270 mOsm.

Description

[Technical field]

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 257,798, filed October 20, 2021, the contents of which are incorporated by reference herein as if set forth in their entirety.

[0002] The present disclosure relates to neonatal care and, more particularly, to saline compositions and methods of use thereof. [Background technology]

[0003] Extreme prematurity is the leading cause of infant morbidity and mortality in the United States. Premature birth occurs for any one of many medical reasons. Respiratory failure is a common and challenging problem associated with extreme prematurity, as gas exchange in severely premature infants is impaired by structural and functional immaturity of the lungs. Despite medical advances in this field, preterm infants, especially those born before 28 weeks of gestation, have a high incidence of chronic lung disease and other complications due to organ immaturity. If a system could be developed that could support normal fetal growth and organ maturation for even a few weeks, it could significantly reduce morbidity and mortality in extremely premature infants and improve the quality of life of survivors. Existing mechanisms to support the premature fetus have drawbacks. Previous attempts to achieve adequate fetal oxygenation in animal models have been limited by circulatory overload and heart failure. Known systems suffer from unacceptable complications such as circulatory failure and contamination.

[0004] In addition to the need for oxygen supply, there is a further need to provide an artificial amniotic fluid that allows the fetus to develop in an environment similar to that of a uterus or extrauterine chamber. In such an environment, the fetus swallows and "inhales" the amniotic fluid, which is then expelled into the uterine chamber. Like biological amniotic fluid, the artificial amniotic fluid accomplishes one or more of the following tasks: allows the developing fetus to move within the chamber, thereby promoting proper bone growth; allows the lungs to develop properly; maintains a constant temperature around the fetus to prevent heat loss; and protects the fetus from external stressors.

[0005] Thus, systems and methods for providing extracorporeal support to a premature fetus or fetus (preterm or mature) that has insufficient respiratory gas exchange to sustain life due to various conditions / disorders may improve survival rates, and such systems and methods require an artificial amniotic fluid or physiological saline solution ("PSS") to replace biological amniotic fluid in order to reduce mortality and morbidity in premature infants.

[0006] At least one or more of the aforementioned needs are met by an extracorporeal support system further comprising various aspects of a fetal chamber assembly system, components, and consumables such as saline solution, and methods of use and preparation of the saline solution are disclosed herein. According to one aspect of the disclosure, a fetal chamber assembly configured to enclose and support a fetus therein includes a base configured to receive a fetus therein, a lid configured to removably contact the base to form a fluid-tight seal between the lid and the base, a growth chamber defined between the base and the lid, the growth chamber configured to receive a fetus therein, and a cannula chamber in fluid communication with the growth chamber, the cannula chamber configured to receive a cannulated umbilical cord of the fetus therein. The growth chamber is configured to be sized to accommodate the fetus during gestation based on the size of the fetus. The fetal chamber assembly is configured to receive a liquid comprising artificial amniotic fluid from a reservoir.

[0007] According to another aspect of the present disclosure, disclosed herein is a physiological saline solution (PSS) comprising an aqueous solvent, about 1.0 mM to about 2.0 mM calcium chloride, about 3.0 mM to about 5.0 mM potassium chloride, about 15.0 mM to about 20 mM sodium bicarbonate, about 90 mM to about 110 mM sodium chloride, and about 9 mM to about 13 mM sodium acetate, wherein the solution has a pH in the range of about 7.0 to about 7.4 and an osmolality in the range of about 250 mOsm to about 270 mOsm.

[0008] In a further embodiment, the method of preparing a saline solution comprises dissolving sodium chloride in an aqueous solvent, dissolving sodium bicarbonate in an aqueous solvent, dissolving potassium chloride in an aqueous solvent, dissolving calcium chloride in an aqueous solvent, and adding a pH adjusting agent to the aqueous solvent comprising a salt in an amount sufficient to adjust the pH to a value of about 7.0 to about 7.4 to provide said saline solution. In this or other embodiments, the method further comprises introducing an additive selected from a growth factor, an antimicrobial peptide, or a combination thereof to the aqueous solvent. In this or other embodiments, the salt comprises an acetate salt, more specifically sodium acetate. [Brief description of the drawings]

[0009] This application is better understood when read in conjunction with the accompanying drawings, in which: For the purpose of illustrating the subject matter, there are shown exemplary aspects of the subject matter, but the presently disclosed subject matter is not limited to the specific methods, apparatus, and systems disclosed. [Figure 1] FIG. 1 is a perspective view of a fetal chamber assembly according to one embodiment of the present disclosure. [Diagram 2] FIG. 2 illustrates the fetal chamber assembly of FIG. 1 showing the lid portion spaced from the base portion. [Diagram 3] FIG. 3 is a perspective view of a base of the fetal chamber assembly of FIGS. 1 and 2 according to one embodiment of the present disclosure. [Figure 4] FIG. 4 shows another perspective view of the base of FIG. [Diagram 5]FIG. 5 is a top view of the base of FIGS. [Figure 6] FIG. 6 shows a perspective view of the lid of the fetal chamber assembly of FIGS. 1-5 according to an embodiment of the present disclosure. [Figure 7] FIG. 7 shows a cross-sectional perspective view of the fetal chamber assembly of FIGS. 1-6. [Figure 8] FIG. 8 is a perspective view of a growth chamber according to one embodiment of the present disclosure showing an upper membrane spaced apart from lower and growth membranes. [Figure 9] FIG. 9 is a cross-sectional perspective view of the growth chamber of FIG. 8 showing the upper membrane in contact with the lower membrane. [Figure 10] FIG. 10 is an exploded view of the lower membrane and growth membrane of the growth chamber of FIGS. [Figure 11] FIG. 11 is a side view of a fetal chamber assembly according to one embodiment of the present disclosure, showing a growth chamber having a first volume. [Figure 12] FIG. 12 is a side view of the fetal chamber assembly of FIG. 11 showing a growth chamber having a second volume. [Figure 13] FIG. 13 is a top view of a fetal chamber assembly showing flow connections according to one embodiment of the present disclosure. [Figure 14A] FIG. 14A is a side cross-sectional view of a meconium sensor assembly according to one embodiment of the present disclosure. [Figure 14B] FIG. 14B is a rear cross-sectional view of the meconium sensor assembly of FIG. 22A. [Figure 15] FIG. 15 is a schematic diagram of a meconium sensor assembly according to another embodiment of the present disclosure. [Figure 16] FIG. 16 is a top view of a fetal chamber assembly according to yet another embodiment of the present disclosure showing an air removal port and an air removal assembly. [Figure 17] FIG. 17 is a front view of an air removal assembly according to one embodiment of the present disclosure. [Figure 18] FIG. 18 is a perspective view of a fetal chamber assembly according to yet another embodiment of the present disclosure, showing an air outlet adjacent to the air removal port. [Figure 19] FIG. 19 is a schematic diagram of a saline circuit according to another embodiment of the present disclosure. [Figure 20] FIG. 20 is a front elevational view of a container according to another embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Aspects of the present disclosure will now be described in detail with reference to the drawings, in which like reference numbers refer to like elements throughout unless otherwise specified.

[0011] The systems disclosed in the present application are configured to provide extracorporeal support to a premature newborn. It should be understood that throughout the present application, "fetus" and "neonatal" may be used interchangeably and the description herein is not limited to only one term or the other. The term "fetus" may be used to refer to both a live fetus in utero and a fetus or newborn removed from the uterus. The terms "artificial amniotic fluid" or "physiological saline" or "PSS" may be used interchangeably and are not limited to only one term or the other. These systems provide an environment substantially similar to the environment that a premature fetus would experience in utero. The survival rate of a premature fetus that has been removed from the uterine environment and is, for example, between about 23 and about 24 weeks of gestation, may be increased by placing the premature fetus in the disclosed system environment. According to some aspects of the present disclosure, the system environment may be configured to: 1) limit the exposure of the premature fetus to light; 2) limit the exposure of the premature fetus to sound; 3) maintain the fetus submerged in a liquid environment; 4) maintain the premature fetus within a desired temperature range; or 5) any combination thereof.

[0012] A premature newborn may be maintained in a suitable environment for a certain period of time to allow the newborn to develop. The environment is preferably as close as possible to a natural uterus so that the development of the newborn is the same as that of a fetus still in the uterus. Once the fetus is removed from the uterus, the fetus may be placed in a fetal growth and development system that at least partially mimics the natural uterus. The fetal system may maintain temperature, fluids, gas exchange, light exposure, physical stimulation, and other parameters favorable to fetal development. The fetal blood vessels may be connected to an external circulatory system. Blood vessels may be cannulated by suitable mechanisms and methods to allow fetal blood to be transferred from the fetus to the external circulatory system (e.g., through a first blood vessel of the fetus), through the external circulatory system, and then back to the fetus (e.g., through a second blood vessel of the fetus). The fetal system may be configured to allow the fetus to remain therein for days, weeks, or months while the fetus grows and develops. The fetal system may be located within, or be part of, a larger assembly or system that maintains chamber parameters favorable to fetal development. Necessary nutrients, gases, and fluids are supplied to the fetal chamber through connected systems, and waste products are removed from the fetal system through one or more connected systems. Examples of fetal systems and related systems compatible with the PSS described herein are described in U.S. Patent Nos. 10,085,907, 10,751,238, 10,864,131, 10,945,903, and U.S. Publication Nos. 2021 / 0161744 and 2021 / 0052453.

[0013] Physiological saline solution (PSS) Described herein is a physiological saline solution (PSS) that is composed of elements necessary for desirable fetal development and has physical and chemical parameters beneficial to fetal growth. It will be appreciated that the liquid must be biocompatible with the fetus such that it does not cause damage to the fetus when it comes into contact with the fetus. It will also be appreciated that the liquid should preferably not be corrosive or damaging to components of the fetal chamber assembly 10 or other elements of the fluid circuit when the liquid is introduced into the fetal chamber assembly or other elements of the fluid circuit. The PSS can be controlled for various parameters such as temperature, pressure, nutrient content, gas content, sterility, and / or other properties. In some embodiments, it may be preferred that the PSS resembles, at least in part, the amniotic fluid found in the uterus of a natural human during pregnancy. In some embodiments, the PSS may include one or more gases dissolved therein.

[0014] In one embodiment, there is PSS having an aqueous solvent, about 1.0 mM to about 2.0 mM calcium chloride, about 3.0 mM to about 5.0 mM potassium chloride, about 15.0 mM to about 20 mM sodium bicarbonate, about 90 mM to about 110 mM sodium chloride, about 9 to about 13 mM sodium acetate, and optionally at least one buffering agent, wherein the solution has a pH ranging from about 7.0 to about 7.4. In this or other embodiments, the solution has an osmolality ranging from about 250 to about 270 mOsm. Examples of aqueous solvents include, but are not limited to, deionized water, distilled water, purified water, and the like.

[0015] In certain embodiments, the PSS further comprises at least one additive selected from growth factors, antimicrobial peptides, and combinations thereof. Depending on certain factors, such as the effect of the additive on the stability and / or physiological efficacy of the solution, the additive is added during the manufacture of the PSS or alternatively added to the PSS within the PSS fluid circuit or other components of the extracorporeal fetal system. In this or other embodiments, other additives that can be added to the PSS are at least one or more amino acids, proteins, carbohydrates, lipids, phospholipids, urea, enzymes, electrolytes, hormones, growth factors, antimicrobial agents, or combinations thereof, to approximate the composition of human amniotic fluid and to aid in the growth and development of the neonatal patient. Examples of amino acids include taurine, glutamine, arginine, ornithine, and combinations thereof. An example of a carbohydrate additive is glucose. Examples of growth factor additives include insulin-like growth factor 1, insulin-like growth factor 2, epidermal growth factor, hepatocyte growth factor, transforming growth factor alpha, transforming growth factor beta-1, erythropoietin, granulocyte colony stimulating factor, and combinations thereof. Examples of antimicrobial peptide additives include human alpha defensin 1-3, human beta defensin-1, human beta defensin-2, human beta defensin-3, human beta defensin-4, bactericidal / permeability increasing protein, lactoferrin, cathelicidin, calprotectin, and combinations thereof.

[0016] As previously mentioned, specific additives to the PSS may include antimicrobial agents and immunomodulators. The addition of one or more of these additives acts as a prophylaxis against pathogens, bacteria, fungi, protozoa, and viruses. Examples of these antimicrobial additives include alpha-defensins [HNP1-3], lactoferrin, lysozyme, bactericidal / permeability-increasing proteins, calprotectin, secretory leukocyte protease inhibitor, psoriasin, cathelicidin, and the like.

[0017] Further additives that can be added to the PSS as therapeutic agents include antibiotics, thyroxine, nutrients (ie, glucose, amino acids, lipids), glucocorticoids, surfactants, beta-adrenergic receptor agonists, and the like.

[0018] In another embodiment, stem cells can be obtained from the amniotic fluid of the neonatal patient's mother prior to the neonatal patient entering the system. The amniotic fluid can be obtained from the mother by amniocentesis or other means and grown in controlled culture to allow the cells to divide and propagate into stem cell lines. These stem cells can be added to the PSS in sufficient amounts to produce the desired therapeutic effect.

[0019] In another aspect, a method for preparing PSS is provided that includes dissolving sodium chloride in an aqueous solvent, dissolving sodium bicarbonate in the aqueous solvent, dissolving potassium chloride in the aqueous solvent, dissolving calcium chloride in the aqueous solvent, and adding a pH adjusting substance to the aqueous solvent. In this or other embodiments, the pH adjusting substance comprises a salt. In this or further embodiments, the salt comprises an acetate, such as, but not limited to, sodium acetate, potassium acetate, magnesium acetate, or combinations thereof. The pH adjusting substance can be added in an amount sufficient to adjust the pH to a value of about 7.0 to 7.4 to provide a saline solution. Optionally, the step of adding a pH adjusting substance further comprises adding hydrochloric acid to the aqueous solvent. In this or other aspects, the method further comprises introducing an additive selected from a growth factor, an antimicrobial peptide, or a combination thereof, to the aqueous solvent. This introducing step may occur before or during use of the PSS in the fluid circuit. In certain embodiments, the PSS solution is a PSS having about 1.0 mM to about 2.0 mM calcium chloride, about 3.0 mM to about 5.0 mM potassium chloride, about 15.0 mM to about 20 mM sodium bicarbonate, about 90 mM to about 110 mM sodium chloride, and about 9 to about 13 mM sodium acetate. In this or other embodiments, the PSS has an osmolality ranging from about 250 to about 270 mOsm. The method steps for preparing the PSS can be performed in any combination or steps (e.g., abcde, acbde, etc.), simultaneously (e.g., during at least a portion of any one or more steps), or sequentially in any other order.

[0020] The method of preparing the PSS may include passing an aqueous solvent through a vessel containing sodium chloride. The method of preparing the PSS may include passing an aqueous solvent through a vessel containing sodium bicarbonate. The method of preparing the PSS may include passing an aqueous solvent through a vessel containing potassium chloride. The method of preparing the PSS may include passing an aqueous solvent through a vessel containing calcium chloride. The method of preparing the PSS may include passing an aqueous solvent through a vessel containing one or more of sodium chloride, sodium bicarbonate, potassium chloride, and calcium chloride. The sodium chloride, sodium bicarbonate, potassium chloride, and calcium chloride may dissolve in the aqueous solvent as it passes through the vessel. The method may include sequentially passing the aqueous solvent through a first vessel containing a first substance and a second vessel containing a second substance. The first substance may be different from the second substance. The first substance may include at least one of sodium chloride, sodium bicarbonate, potassium chloride, and calcium chloride. The second substance may include at least one of sodium chloride, sodium bicarbonate, potassium chloride, and calcium chloride. The method may include passing the aqueous medium through a vessel containing a pH modifying substance such that the pH of the aqueous medium is modified. The pH adjusting substance may include sodium acetate. The method may include passing the aqueous medium through a vessel containing an additive selected from a growth factor, an antimicrobial peptide, or a combination thereof.

[0021] The method of preparing PSS may include combining an aqueous solvent with a first solution. The first solution may be a fluid. Combining the aqueous solvent with the first solution may include diluting the first solution from a first concentration to a second concentration. The second concentration may be about 99% to about 90%, about 90% to about 80%, about 80% to about 70%, about 70%% to about 60%, about 60% to about 50%, about 50% to about 40%, about 40% to about 30%, about 30% to about 20%, about 20% to about 10%, or about 10% to about 1% of the first concentration. The first solution may include sodium chloride. The first solution may include sodium bicarbonate. The first solution may include potassium chloride. The first solution may include calcium chloride. The first solution may include one or more of sodium chloride, sodium bicarbonate, potassium chloride, and calcium chloride.

[0022] A method of preparing a PSS may include passing an aqueous solvent through a substance generator. The substance generator may be an electrolytic cell. The substance generator may generate a first substance to be combined with the aqueous solution. The first substance may include sodium chloride. The first substance may include sodium bicarbonate. The first substance may include potassium chloride. The first substance may include calcium chloride. The first substance may include at least one of sodium chloride, sodium bicarbonate, potassium chloride, and calcium chloride.

[0023] In Vitro Fetal System Various aspects of fetal systems and other related systems are disclosed throughout this application. In an exemplary preferred embodiment as shown in Figures 1 and 2, a fetal chamber assembly 10 includes a base 100 and a lid 112. A growth chamber 120 configured to receive a fetus 1 therein is defined in an interior space j104 between the base 100 and the lid 112. The cannulated umbilical cord 2 of the fetus is disposed in a cannula chamber 150 having a wall structure that forms an opening to the growth chamber 120. In the preferred embodiment shown, the growth chamber 120 is configured to be adjustable in size to receive different sized fetuses and accommodate the growth of the fetus during gestation while the fetus is within the fetal chamber assembly 10. A liquid having favorable characteristics for fetal development is introduced and flowed through the growth chamber 120 and the cannula chamber 150. The fetus 1 can be housed within the fetal chamber assembly 10 for a desired amount of time until it reaches a predetermined stage of pregnancy, and the fetus 1 can be monitored and maintained during its development process within the system 10. The fetal chamber assembly 10 can include various sensors and ports, described in detail below, which monitor and maintain fetal vitals and the status of the system 10, introduce materials necessary for fetal development, and assist in removing contaminants or components of the system 10 as needed.

[0024] As shown in FIGS. 1 and 2, the fetal chamber assembly 10 includes a base 100 and a lid 112. The lid 112 can be removably attached to the base 100 such that a fluid-tight seal can be selectively formed between the lid 112 and the base 100. The system 10 can have a closed configuration in which the lid 112 and the base 100 form a fluid-tight seal therebetween, and an open configuration in which there is no fluid-tight seal between the lid 112 and the base 100. In some embodiments, the lid 112 is completely removable from the base 100 such that the lid 112 does not contact the base 100 and is spaced apart from the base 100. In some embodiments, the lid 112 is hingedly attached to the base 100 such that the lid 112 can pivot toward or away from the base 100 along the hinged attachment. In some embodiments, a hinged attachment (not shown) may be releasable so that the lid 112 can be completely separated from the base 100 .

[0025] In some embodiments, the lid 112 may be configured to be secured to the base 100 via one or more locking elements that may be selectively locked or unlocked to secure or remove the lid 112 from the base 100, respectively. In some exemplary embodiments (see, e.g., FIG. 2), the base 100 may include one or more fasteners 300 disposed thereon, and the lid 112 may include one or more protrusions 304 designed to be clamped by the fasteners 300 disposed thereon. Another view of the lid 112 is depicted in FIG. 6. The fasteners 300 on the base 100 may be configured to releasably engage the protrusions 304 on the lid 112. Other locking elements are contemplated and the disclosure is not intended to be limited to the particular locking elements 300, 304 depicted in the figures, and it will be understood that the fasteners 300 can be reversed such that the fasteners 300 are on the lid 112 and the prongs 304 are on the base 100. The system 10 may include multiple locking elements, which may be the same or different types of locking elements. Although the figures depict eight fasteners 300 configured to engage eight prongs 304, it will be understood that another suitable number of respective base and lid closure elements, such as 1, 2, 3, . . . , 10, etc., may be utilized. Easy and quick removal of the lid 112 is beneficial in the event of a medical emergency where a user needs to access a fetus within the interior of the fetal chamber assembly 10.

[0026] 3-5, a base 100 according to one embodiment of the present disclosure is depicted. The base 100 includes a housing 108 that provides a rigid structure to the base 100 and may include various ports, sensors, and channels therein, as will be described in detail below. The base 100 further includes a growth chamber 120 configured to receive a fetus therein, and a cannulated chamber 150 configured to receive a cannulated umbilical cord of the fetus. A suitable fluid is introduced into the system 10, for example, into the housing 108, causing the fluid to flow through the growth chamber 120 and through the cannulated chamber 150.

[0027] The growth chamber 120 may be at least partially enclosed by the housing 108. In some embodiments, the growth chamber 120 may be disposed in an opening extending through the housing 108 along a vertical direction z. The growth chamber 120 may be separated from the housing by a seal 296 extending along at least a portion of the growth chamber 120. The seal 296 of the base 100 may be configured to releasably contact the lid 112 to form a liquid-tight seal between the base 100 and the lid 112. In some examples, the lid 112 may include a respective seal (not shown) configured to contact the seal 296 on the base 100. A first inlet 194 for introducing the PSS or related liquid into the growth chamber and an outlet 202 for exhausting the PSS or related liquid from the growth chamber are defined on the growth chamber 120. It may be preferable to position the first inlet 194 and the outlet 202 so that the liquid enters the growth chamber 120 adjacent the fetal head, flows substantially along a longitudinal direction y from the fetal head towards the fetal feet, and exits the growth chamber 120 adjacent the fetal feet. The positioning of the liquid inlets and outlets is described further below.

[0028] The growth chamber 120 is configured to receive and contain the fetus during growth within the system 10. Referring to FIG. 7, which illustrates a cross-sectional view of the system 10 in a closed configuration, the growth chamber 120 is defined, at least in part, by a lower membrane 128 attached to the housing 108 and an upper membrane 124 disposed on the lid 112. In some embodiments, the growth chamber 120 is further defined by the seal 296 that extends circumferentially around the growth chamber 120. The seal 296 can include one or more bumpers 294 thereon that extend inwardly toward the growth chamber 120 and act as a physical barrier against which a fetus may come into contact while within the growth chamber 120. The bumpers 294 are configured to be sufficiently soft and malleable to deform or dent when contacted by a fetus. The bumper 294 separates the growth chamber from the rigid housing 108 and prevents the fetus from being injured by contact with sharp edges or rigid portions of the housing 108. The bumper 294 may extend at least partially around the periphery of the growth chamber 120. The bumper 294 may extend between the lower membrane 128 and the upper membrane 124 along the vertical direction z. In some embodiments, the bumper 294 may be disposed external to the growth chamber 120 such that at least one of the upper membrane 124 and the lower membrane 128 is disposed between the bumper 294 and a fetus located within the growth chamber 120.

[0029] 7-10, the upper membrane 124 of the growth chamber 120 is spaced apart from the lower membrane 128 along a vertical direction z. The growth chamber 120 is configured to receive a fetus in a space between the upper membrane 124 and the lower membrane 128. When the system 10 is moved to the closed configuration and the lid 112 is secured to the base 100, the upper membrane 124 is moved over the fetus and the lower membrane 128. The upper and lower membranes 124, 128 may be the same shape or may be different shapes. For example, as shown, the lower membrane 128 may be concave and recessed in the vertical direction z away from the upper membrane 124. The concave shape may facilitate placement of a fetus on the lower membrane 128. The upper membrane 124 may be substantially flat in a plane defined by a lateral direction x and a longitudinal direction y. In some aspects, the upper membrane 124 may be concave, with the concave surface extending in a vertical direction z away from the lower membrane 128 (i.e., opposite the concave surface extending from the lower membrane 128). The upper membrane 124, the lower membrane 128, or both membranes may be configured to stretch when a force is applied, e.g., in the vertical direction z, such that one or each of the concave surfaces deepens in the respective direction. In some preferred embodiments, the lower membrane 128 may be configured to stretch to deepen its concave surface, thereby allowing the volume of the growth chamber 120 to be increased.

[0030] Growth chamber The growth chamber 120 can be configured to vary in size based on parameters of the system 10. This is advantageous to allow the growth chamber 120 to accommodate fetuses of different sizes and to accommodate fetuses that grow while residing within the system 10. In some circumstances, it may be medically preferable to accommodate the fetus in a growth chamber that is commensurate with the size of the fetus. That is, it may be undesirable to accommodate and hold the fetus in a growth chamber that is too large. In particular, it may be preferable to prevent the fetus from being placed in an unnecessarily large volume where the fetus may be exposed to undesirable movement or entanglement of the umbilical cord. Such entanglement may place undesirable pressure or strain on the umbilical cord, which may result in occlusion of blood flow through the umbilical cord. During pregnancy, it may be medically desirable to ensure that the fetus is in a small enough space that it cannot move excessively or change positions in the growth chamber 120 in a potentially harmful manner. Such positioning may cause injury to the fetus, strain or damage to the umbilical cord, or accidental bleeding of the umbilical cord. Conversely, it is undesirable to hold a fetus in a growth chamber that is too small for the fetus. Restraining the fetus in the growth chamber 120 can increase pressure on the fetus and / or prevent the fetus from achieving desirable physical growth. Controlling the position of the fetus also helps to keep the fetus' head away from areas in the growth chamber 120 where there is an increased risk of meconium expulsion. Furthermore, controlling the position of the fetus allows for the placement of various sensors and transducers in the system 10 relative to where the fetus is expected to be located in the growth chamber 120. Thus, the system 10 advantageously has the growth chamber 120 that can be sized to accommodate fetuses of various sizes. It is further preferable to have the ability to increase the size of the growth chamber 120 as the fetus grows while residing in the system 10 to accommodate the corresponding increase in size of the fetus.

[0031] The growth chamber 120 may be configured to vary between a number of different volumes, with each different volume being associated with a corresponding size of a fetus. With general reference to FIGS. 7-12, the growth chamber 120 may have an upper membrane 124 and a lower membrane 128, as described above. The growth chamber 120 may further include a growth membrane 132 generally spaced apart from the lower membrane 128 along the vertical direction z. In some aspects, the growth membrane 132 may be positioned such that the lower membrane 128 is disposed between the upper membrane 124 and the growth membrane 132. In some preferred embodiments, the lower membrane 128 and the growth membrane 132 may be secured to one another along their respective peripheries, for example, by welding, heat sealing, clamps, adhesives, or other suitable fastening mechanisms.

[0032] A fluid pocket 136 is defined between the lower membrane 128 and the growth membrane 132. The fluid pocket 136 is configured to receive a fluid therein such that the fluid is retained between the lower membrane 128 and the growth membrane 132. The fluid may include a liquid and / or a gas. In some preferred embodiments, the fluid is a liquid, such as saline. In some aspects, it may be preferred that the fluid in the fluid pocket 136 is a liquid so that diagnostic tests, such as ultrasound, can be performed on the growth chamber 120. It will be appreciated that in some embodiments, the fluid may alternatively include a gas. The fluid in the fluid pocket 136 is a stationary fluid configured to not come into contact with the interior of the growth chamber 120, a fetus in the growth chamber 120, or any liquids or components in the growth chamber 120.

[0033] The fluid may be introduced to the fluid pocket 136 via a fluid pocket port 140 (shown in FIG. 10 ) disposed on the growth chamber 120 and in fluid communication with the fluid pocket 136. In some embodiments, the fluid pocket port 140 may be disposed on the lower membrane 128. In other embodiments, the fluid pocket port 140 may be disposed on the growth membrane 132. In some embodiments, the fluid pocket port 140 may be disposed between the lower membrane 128 and the growth membrane 132. The more the fluid is introduced into the fluid pocket 136, the larger the volume within the fluid pocket 136. During operation of the system 10, the fluid may be selectively added to or removed from the fluid pocket 136.

[0034] The growth chamber 120 is configured to have at least a first volume and a second volume different from the first volume. It will be understood that the growth chamber 120 may be configured to be adjusted to have any number of different volumes, and reference to a first volume or a second volume is meant as a descriptive comparison of the two volumes of the growth chamber 120. With reference to FIG. 11, an exemplary configuration of the growth chamber 120 having a first volume is depicted. The first volume is defined between the lower membrane 128 and the upper membrane 124. The lower membrane 128 is spaced from the growth membrane 132 via the fluid described above. The first volume is configured to accommodate a fetus 1 having a first size. With reference to FIG. 12, an exemplary configuration of the growth chamber 120 is depicted having a second volume larger than the first volume. The second volume is configured to accommodate a fetus 1 having a second size larger than the first size. As shown in Figure 12, the lower membrane 128 may not be spaced from the growth membrane 132. This means that there is no fluid in the fluid pocket 136. Thus, Figure 12 illustrates the maximum volume possible for the embodiment of the growth chamber 120 depicted in Figures 11 and 12.

[0035] The specific volume of the growth chamber 120 may be inversely proportional to the volume of the fluid pocket 136. That is, as more fluid is introduced into the fluid pocket 136 and the volume of the fluid pocket 136 increases, the volume of the growth chamber 120 configured to receive a fetus therein decreases. Conversely, as fluid is removed from the fluid pocket 136 and the volume of the fluid pocket 136 decreases, the volume of the growth chamber 120 increases. The volume of the growth chamber 120 may be defined between the upper membrane 124 and the lower membrane 128. The growth chamber 120 may be configured to vary the volume along a vertical direction z, along a lateral direction x, along a longitudinal direction y, or along a combination of some or all of the directions. In some embodiments, the volume within the growth chamber 120 can be varied three-dimensionally such that as the growth chamber volume increases, the growth chamber 120 increases in size along the vertical direction z, the lateral direction x, and the longitudinal direction y, and as the growth chamber volume decreases, the growth chamber 120 decreases in size along the vertical direction z, the lateral direction x, and the longitudinal direction y.

[0036] The fetus 1 may be disposed on the lower membrane 128, specifically on the side of the lower membrane 128 that faces the upper membrane 124 and defines the volume of the growth chamber 120. The other side of the lower membrane 128 may partially define the fluid pocket 136 and may be in contact with the fluid in the fluid pocket 136. The fluid in the fluid pocket 136 supports the lower membrane 128. In the embodiment depicted in FIGS. 7-12, the fluid pocket 136 is disposed below the lower membrane 128 along a vertical direction z. For purposes of this disclosure, the vertical direction z may have a non-zero vector component that is parallel to gravity. In some embodiments, the vertical direction z is perfectly parallel to gravity. Thus, the lower membrane 128, disposed vertically above and supported by the fluid in the fluid pocket 136, is acted upon by gravity along the vertical direction z, and the fluid in the fluid pocket 136 exerts a counteracting normal force on the lower membrane 128 commensurate with the weight of the lower membrane 128. Gravity acts on the fluid in the fluid pocket 136 along the vertical direction z, as well as on the fetus 1, as well as other components of the system 10, such as PSS, disposed on the lower membrane 128. As the amount of fluid in the fluid pocket 136 decreases, the level of support of the lower membrane 128 by the fluid in the fluid pocket 136 decreases as well. Thus, gravity causes the lower membrane 128 to stretch, deform, and / or unfold along the lateral direction x and / or longitudinal direction y, and sag more downward along the vertical direction z, toward the fluid pocket 136. As the lower membrane 128 moves downward along the vertical direction z, away from the upper membrane 124, the volume within the growth chamber 120 increases. Conversely, as the amount of fluid in the fluid pocket 136 increases, the support level of the lower membrane 128 similarly increases, causing the lower membrane to protrude upwardly along the vertical direction z towards the upper membrane 124, thereby decreasing the volume of the growth chamber 120 defined between the upper and lower membranes 124, 128. Thus, in one embodiment, the lower and growth membranes 128, 132 function as a variable volume bladder mechanism.

[0037] In operation, when the fetus 1 is introduced into the growth chamber 120, the fetus 1 has a first size and the growth chamber 120 has a first volume. The fetus 1 may be introduced onto the lower membrane 128 along with the PSS and other components of the system 10. The fluid pocket 136 may contain a first amount of fluid therein configured to provide support to the lower membrane 128 against gravity and commensurate with the weight of the fetus 1, the lower membrane 128, the PSS, and other components in the growth chamber 120 contacting the lower membrane 128. As the fetus 1 grows to a second size, it may be desirable to increase the volume of the growth chamber 120 by an amount corresponding to the growth of the fetus 1. To do this, fluid may be removed from the fluid pocket 136 via the fluid pocket port 140 such that the fluid pocket 136 contains a second amount of fluid therein that is less than the first amount. The reduction in fluid and the physical support provided by the fluid causes the lower membrane 128 to expand in one or more of the lateral direction x, longitudinal direction y, and vertical direction z, thus increasing the volume of the growth chamber 120 to a second volume.

[0038] The process of adjusting the volume within the growth chamber 120 may be manual or automatic. In some embodiments, a user (e.g., a doctor or nurse) may selectively introduce or remove fluid from the fluid pocket 136 to change the volume within the growth chamber 120. In some embodiments, a controller and processor may be configured to communicate with the system 10 to automatically add or remove fluid to or from the fluid pocket 136. The volume adjustment process may be based on the weight, position, age, health, or another parameter of the fetus 1. In some embodiments, the volume adjustment may be based on a specific timeline, such as, for example, daily, every other day, weekly, biweekly, monthly, etc. In some embodiments, the weight of the fetus 1 may be estimated using a derived formula related to ultrasound measurements of the fetus 1 within the growth chamber 120.

[0039] The top, bottom, and growing films 124, 128, 132 may comprise polyurethane, polypropylene, polyethylene, acrylic, polyvinyl chloride, ethylene vinyl acetate, polyvinylidene chloride, or other plastics, or laminated combinations of plastics. In some embodiments, the top film 124, the bottom film 128, the growing film 132, two of the above, or all of the above may comprise thermoplastic urethane. In some embodiments, the top, bottom, and growing films 124, 128, 132 may all comprise the same material, or alternatively, they may be composed of different materials. In some embodiments, the thickness of each of the films may be the same, or the thickness may vary between at least two of the films. In some specific embodiments, the growing film 132 may be thicker than the top film 124, the bottom film 128, or both. In some embodiments, the growing film 132 may be about twice as thick as the top film 124 and / or the bottom film 128. In some embodiments, the top, bottom, and / or growth films 124, 128, 132 can have a durometer scale between about 50 and about 100, between about 60 and about 90, between about 70 and about 80, or a range overlapping one or more of the above ranges. In some embodiments, the films 124, 128, and / or 132 can be formed to have a particular shape (see, e.g., FIGS. 8-10). In some embodiments, it may be advantageous for the top film 124, the bottom film 128, and / or the growth film 132 to be transparent. In some embodiments, it may be advantageous for the top film 124, the bottom film 128, and / or the growth film 132 to be acoustically transparent such that ultrasound may be permitted to pass therethrough without unwanted interference or echoes.

[0040] It will be appreciated that at least the surfaces of the upper and lower membranes 124, 128 that oppose one another, define the growth chamber 120, and are configured to contact the fetus 1 are constructed of a biocompatible material suitable for remaining exposed to the fetus 1 and components of the system 10 within the growth chamber (e.g., the PSS). In some embodiments, it may be advantageous to ensure that at least the upper and lower membranes 124, 128 (specifically, at least the respective surfaces disposed within the growth chamber 120) are substantially smooth and devoid of texture or roughness that may promote bacterial growth thereon.

[0041] The particular size, shape, and dimensions of the growth chamber 120 depend on the intended use, the size of the fetus, and manufacturing constraints. In some exemplary embodiments, the growth chamber 120 can have a first dimension measured along a longitudinal direction y of between about 3 inches and about 20 inches, between about 7 inches and about 16 inches, between about 10 inches and about 12 inches, or another suitable range. The growth chamber 120 can have a second dimension measured along a transverse direction x of between about 3 inches and about 14 inches, between about 5 inches and about 12 inches, between about 7 inches and about 10 inches, or another suitable range. The growth chamber 120 can have a third dimension measured along a longitudinal direction y of between about 2 inches and about 12 inches, between about 4 inches and about 8 inches, or another suitable range.

[0042] Flow path through the fetal chamber assembly In operation, fetal chamber assembly 10 is configured to receive a suitable fluid therein for flowing through said growth chamber 120 and said cannulation chamber 150. The fluid within said cannulation chamber 150 and within said growth chamber 120 may contact a fetus within said growth chamber 120 and the umbilical cord of said fetus.

[0043] The PSS is introduced into the fetal chamber assembly 10 from a PSS source. In some embodiments, it may be preferred that the PSS not remain stagnant within the fetal chamber assembly 10, but instead be moved at a favorable flow rate. Avoiding stagnant liquids may help prevent bacterial growth within the fetal chamber assembly 10. Rather than continuously circulating the same PSS in a closed loop within the fetal chamber assembly 10, the fetal chamber assembly 10 may be configured to pass new, i.e., fresh, PSS through the fetal chamber assembly 10 as it enters, moves through, and then exits the fetal chamber assembly 10. Introducing new PSS instead of circulating the same PSS may help prevent bacterial growth and accumulation, and remove contaminants from the fetal chamber assembly 10, providing better gas and nutrient exchange for the developing fetus.

[0044] 13, an exemplary PSS flow path is depicted within the base 100 of the fetal chamber assembly 10. It will be understood that other suitable flow paths may be used and the exact arrangement of the flow paths as shown is not intended to be limiting. The PSS is introduced into the fetal chamber assembly 10 from a PSS source and split into two separate inlets, a first inlet 194 and a second inlet 198. As briefly described above, the first inlet 194 is defined within the growth chamber 120 such that the PSS from the first inlet 194 is moved into the growth chamber 120, and the second inlet 198 is defined in the cannula inlet 162 of the cannula chamber 10 such that the PSS from the second inlet 198 is moved into the cannula chamber 150. The PSS is configured to move generally along a longitudinal direction y toward the outlet 202. The outlet 202 is spaced apart from the first and second inlets 194, 198 along the longitudinal direction y. In some embodiments, the outlet 202 is positioned in the growth chamber 120 opposite the first inlet 194 such that the fetus may be positioned between the first inlet 194 and the outlet 202. The first inlet 194 may be positioned in the growth chamber 120 closer to the fetus' head than to the fetus' feet, while the outlet 202 may be positioned closer to the fetus' feet than to the fetus' head. This causes the PSS flowing from the first inlet 194 towards the outlet 202 to generally flow in a direction from the fetus' head towards the fetus' feet. As described in more detail below, the fetal chamber assembly 10 may be rotated along different axes, however, it may be preferable to maintain the orientation of the fetal chamber assembly 10 such that the outlet 202 is located at the lowest point of the growth chamber 120 (relative to gravity) so that the PSS flows downwardly towards the outlet 202 due to gravity.Such a flow path may be advantageous in directing contaminants (e.g., meconium) away from the fetal head by having a continuous flow of PSS that may move any contaminants toward the feet and toward the outlet 202, rather than moving the contaminants toward or adjacent to the fetal head. Because aspiration of contaminants (such as meconium) can cause respiratory complications and impede fetal development, it may be preferable to maintain a flow of PSS that directs contaminants and foreign objects away from the fetal head.

[0045] An outlet channel 206 extends from the outlet 202 and leads to a waste receptacle configured to receive the PSS after it has traveled through the fetal chamber assembly 10. The outlet channel 206 may be disposed at least partially within the housing 108. The outlet channel 206 may be configured to allow the PSS flowing therethrough to contact, flow adjacent to, or flow through one or more components of the fetal chamber assembly 10. With reference to FIG. 13, for example, a meconium sensor assembly 292 may be disposed on or adjacent the outlet channel 206 such that the PSS liquid flowing through the outlet channel 206 is sensed by the meconium sensor assembly 292, as described in more detail below.

[0046] In some embodiments, the fetal chamber assembly 10 may include multiple outlets 202. Each outlet 202 may be configured to be in fluid communication with the same outlet channel 206 or may be configured to be in fluid communication with a separate outlet channel 206.

[0047] In operation, the PSS enters the fetal chamber assembly 10 through the first and second inlets 194, 198 and flows toward the outlet 202. Although the fetal chamber assembly 10 is depicted as having a partition wall 158 separating the growth chamber 120 and the cannula chamber 150, it should be understood that the partition wall 158 may have different dimensions in different embodiments and the flow of the PSS liquid may be affected by the particular placement of the partition wall 158. For example, as seen in Figures 2-4, the partition wall 158 extends upward from the housing 108 (towards the lid 112 when the fetal chamber assembly 10 is closed) along a vertical direction z. In some preferred embodiments, the partition wall 158 may be configured to extend in a vertical direction z such that the upper surface of the partition wall 158 is between the housing 108 through which the partition wall 158 extends and a plane defined by the lateral direction x and the longitudinal direction y in which the upper surface of the seal 296 is disposed. Simply stated, the height of the partition wall 158 (measured in the vertical direction z from the housing 108) is less than the height of the seal 296. In such an embodiment, when the fetal chamber assembly 10 is closed and the lid 112 is sealingly secured to the base 100, the PSS liquid can pass over the partition wall 158 in the space defined between the partition wall 158 and the lid 112. Such an embodiment may be preferred to reduce areas of stagnant liquid within the fetal chamber assembly 10, thus reducing the prevalence of bacterial growth. Furthermore, such an embodiment may make it simpler to close the fetal chamber assembly 10 since only a single seal 296 may be used. In some alternative embodiments, the partition 158 may be configured to have a height such that the top of the partition 158 matches the height of the seal 296, such that when the fetal chamber assembly 10 is closed, no space is defined between the partition 158 and the lid 112 and the PSS is not permitted to pass over the partition 158.

[0048] The PSS may be introduced into the fetal chamber assembly 10 from a single source using a single pump. In the fetal chamber assembly 10, the PSS may be split into two (or more) inlets as described above. In some preferred embodiments, each inlet does not have a separate pump or similar mechanism for moving the PSS thereto independently from the other inlets. In this manner, the distribution of the amount of PSS between the individual inlet ports does not need to be actively controlled. Still referring to FIG. 13, each of the first and second inlets 194, 198 may be configured to receive either the same amount of PSS or different amounts of PSS depending on the parameters of the fetal chamber assembly 10. Similarly, the PSS introduced through each of the first and second inlets 194, 198 can have substantially the same pressure or different pressures.

[0049] In some embodiments, the amount of PSS introduced into each of the first and second inlets 194, 198 depends on the position of the fetal chamber assembly 10, more specifically the position of the first and second inlets 194, 198 relative to one another. The distribution of PSS between the different inlets depends on the pressure difference of the PSS directed to each inlet. The relative position of each inlet may vary based on how the fetal chamber assembly 10 is positioned, and the fetal chamber assembly 10 may translate in one, two, or three directions and may rotate along multiple axes. For purposes of this discussion, the fetal chamber assembly 10 may translate along a lateral direction x, along a longitudinal direction y, and / or along a vertical direction z. The fetal chamber assembly 10 may rotate along a pitch axis parallel to the lateral direction x, along a roll axis parallel to the longitudinal direction y, and / or along a yaw axis parallel to the vertical direction z. The specific locations of each of the pitch, roll, and yaw axes relative to the fetal chamber assembly 10 may vary among various embodiments and are not intended to be limiting of the following description unless otherwise indicated. The fetal chamber assembly 10 may be configured to rotate about other axes as well, and embodiments in the present disclosure are not limited to the pitch, roll, and yaw axes discussed above.

[0050] For example, referring to the exemplary arrangement of the first and second inlets 194, 198 shown in FIG. 13 (also seen in FIG. 3), the first and second inlets 194, 198 are shown to be in the same plane defined by a lateral direction x and a longitudinal direction y. In such an arrangement, the PSS introduced into the two inlets can have the same pressure. In this manner, the flow rate of the PSS can be equal at the first and second inlets 194, 198. When the fetal chamber assembly 10 is rotated in a first direction about the roll axis, one of the first and second inlets 194, 198 is positioned higher (along a vertical direction z, relative to the ground) than the other of the first and second inlets 194, 198. The fetal chamber assembly 10 can be rotated about the roll axis in a second direction opposite to the first direction such that the relative arrangement of the first and second inlets 194, 198 is reversed. The higher inlets will have a lower pressure of the PSS than the lower inlets. The further the fetal chamber assembly 10 rotates along the roll axis, the greater the relative distance between the first and second inlets 194, 198 and the greater the pressure differential. The lower one of the first and second inlets 194, 198 will receive proportionally more of the PSS liquid therein compared to the other inlet. Exemplary, non-limiting pitch and roll axes according to one embodiment are depicted in FIG.

[0051] This distribution may be due to a mechanism (e.g., a pump) configured to introduce the PSS into the fetal chamber assembly 10. The pump may be configured to move the PSS into the fetal chamber assembly 10 but not actively direct flow to a particular inlet. That is, the pump is configured to move the PSS liquid into the fetal chamber assembly 10, but the liquid flows in the direction of least resistance. When the first and second inlets 194, 198 are in the same horizontal plane defined by the lateral direction x and the longitudinal direction y, the flow may move equally to both inlets since both inlets have the same resistance. When the fetal chamber assembly 100 is rotated in the first direction along the roll axis, an inlet that is higher along the vertical direction z (relative to the ground) will have more resistance to flow than an inlet that is lower relative to the ground.

[0052] In some embodiments, a second mechanism for moving the liquid (e.g., a second pump) may be disposed in fluid communication with the outlet channel 206 and configured to facilitate movement of the PSS within the outlet channel 206 out of the fetal chamber assembly 10.

[0053] meconium sensing During pregnancy, a fetus may occasionally shed meconium into its immediate environment. While meconium itself is generally sterile, its presence within the fetal chamber assembly 10 may increase the risk of bacterial growth. Meconium may clog or damage components within the fetal chamber assembly 10, potentially impeding fetal development. In some cases, the fetus may aspirate meconium, which may lead to fetal health problems, such as infection. As such, it is desirable to monitor for the presence of meconium during operation of the fetal chamber assembly 10. If meconium is detected, it may be removed from the fetal chamber assembly 10, as described in more detail below.

[0054] 2-5, a meconium sensor assembly 292 may be disposed on the base housing 108 of the base 100. The meconium sensor assembly 292 is configured to detect the presence of meconium within the fluid (e.g., PSS) flowing through the fetal chamber assembly 10. It will be appreciated that the fetal chamber assembly 10 may include multiple meconium sensor assemblies 292 strategically positioned, for example, within the cannula chamber 150, within the growth chamber 120, or in another portion of the fetal chamber assembly 10.

[0055] In some preferred embodiments, the meconium sensor assembly 292 may be disposed within or adjacent to the outlet channel 206, as shown, for example, in FIGS. 13, 14A, and 14B1. The meconium sensor assembly 292 may be in-line with the outlet channel 206. FIG. 15 shows an exemplary non-limiting schematic diagram of an example arrangement of the meconium sensor assembly 292 disposed adjacent to the outlet channel 206. It will be understood that this schematic diagram is not shown to scale and other arrangements may be utilized. The meconium sensor assembly 292 includes a meconium sensor assembly housing 313 and a sensor 310. The liquid within the outlet channel 206 may enter the sensor assembly housing 313. The sensor 310 is configured to detect the presence of meconium within the liquid within the sensor assembly housing 313. It will be understood that a certain threshold amount of meconium may be predetermined for operation of the fetal chamber assembly 10. As the liquid enters the outlet channel 206 at the outlet 202, the liquid travels along the outlet channel 206 and exits the fetal chamber assembly 10. After the liquid travels to the outlet channel 206, the liquid may pass through or be adjacent to the meconium sensor assembly 292.

[0056] If the sensor 310 detects the presence of meconium in the fluid above a predetermined threshold, the meconium sensor assembly 292 can cause the fetal chamber assembly 10 to notify a user, trigger an alarm, or modify its operation in response to the detected meconium. Locating the meconium sensor assembly 292 within the outlet 206 is advantageous for accurate detection of meconium by the flow of fluid through the fetal chamber assembly 10. As explained above, the flow of fluid moves generally in a direction from the first and second inlets 194, 198 toward the outlet 202, and as such moves generally in a direction from the fetal head toward the fetal feet. Meconium excreted by the fetus is carried by the flow of fluid toward the outlet 202 and may enter the outlet channel 206. As explained above, the relative location of the inlets 194, 198 and the outlet 202, as well as the general shape of the chamber assembly 120 and the cannula chamber 150, serve to reduce areas where stagnant fluid and bacteria may grow within the growth chamber 120 or the cannula chamber 150. Thus, the advantageous design and location of components also serves to direct most or all of the excreted meconium to the outlet 202, such that the amount of meconium detected by the meconium sensor assembly 292 represents a more accurate amount of meconium being excreted by the fetus.

[0057] As briefly described above, the meconium sensor assembly 292 includes the sensor assembly housing 313 and the sensor 310. The sensor 310 may be a spectral sensor including a camera 311 configured to be directed toward a reflector surface 312. The reflector surface 312 may be a Lambertian reflector. The reflector surface 312 may include polytetrafluoroethylene (PTFE). In some embodiments, the reflector surface 312 may include a single color. In some embodiments, the reflector surface 312 may be white. A light source 315 may be disposed on or adjacent to the camera 311 at a predetermined distance from the reflector surface 312. The light source 315 may direct light toward the reflector surface 312 such that at least a portion of the light is reflected from the reflector surface 312 toward the camera 311. The camera 311 is positioned opposite the reflector surface 312 such that the sensor assembly housing 313, including the liquid flowing therethrough, is disposed between the camera 311 and the reflector surface 312. In some embodiments, the outlet channel 206 extends through or is aligned with the sensor housing 213 .

[0058] The liquid moving through the outlet channel 206 can move into the sensor assembly housing 313 adjacent to the sensor 310. When in the sensor assembly housing 313, the liquid can thus pass between the camera 311 and the reflector surface 312. The camera 311 can be a single pixel camera configured to detect an optical change (relative to a predetermined value) of the liquid between the camera 311 and the reflector surface 312. For example, in some embodiments, the camera 311 can be configured to detect the relative intensity of two or more wavelengths. The camera 311 must be able to see the reflector surface 312. Therefore, the material between the camera 311 and the reflector surface 312 must be at least semi-transparent so that the camera can see the reflector surface 312 and detect color. This arrangement allows light reflection from any substances that may be present in the liquid passing through the outlet channel 206, as well as light reflection from the reflector surface 312, which acts as a constant background for measuring the spectral coverage. In some embodiments, the sensor assembly housing 313 may include a first transparent or translucent window 314 disposed on the sensor assembly housing 313 between the camera 311 and the reflector surface 312. A second transparent or translucent window 316 may also be disposed on the sensor assembly housing 313 opposite the first window 314 and between the camera 311 and the reflector surface 312. The camera 311 may be configured to view the reflector surface 312 through the first window 314, through the sensor assembly housing 313 and the liquid therein, and through the second window 316. It will be appreciated that in some aspects, additional windows may be disposed on the sensor 310, the sensor assembly housing 313, or elsewhere on the fetal chamber assembly housing 108.

[0059] The sensor 310 may include a controller 318 having a processor configured to detect color changes different from the reflector surface 312 using the camera 311. The processor may include a program that defines a preferred color spectrum range of interest. Different materials or components disposed between the camera 311 and the reflector surface 312 may have different colors. In a preferred embodiment, the processor may be configured to identify a color range that is consistent with the color of meconium. In some aspects, the color range may include red, yellow, brown, combinations of the above, or related colors. If a color within the programmed range is detected, it may indicate the presence of a particular substance. In a preferred embodiment, for example, if the camera 311 detects red, yellow, brown, or similar colors, this may indicate the presence of meconium.

[0060] In some embodiments, the sensor 310 may be configured to detect six different wavelengths in the visible or near infrared spectrum. The visible spectrum has the ability to convert individual spectral readings into RGB or HSV values. In some embodiments, HSV may have the advantage over RGB of having an intuitive way of interpreting color by using color mapping to a 3D polar space based on measured hue, saturation, and value. In such an exemplary embodiment, a hue measurement may be used to quantify the detected color in a 360 degree space, a saturation measurement may be used to quantify the amount of color as a percentage, and a value measurement may be used to quantify the brightness as a percentage. Regions in the 360 ​​degree space may be associated with specific substances (e.g., meconium or blood). Such measurements allow for accurate detection and quantity of the substance of interest. By configuring a processor to focus on relevant regions in the HSV space, a specific substance of interest may be monitored while ignoring the presence of substances not of interest that may be associated with other regions of the HSV space.

[0061] In some embodiments, the blood sensor may be an optical sensor that detects the presence of blood by the absorption of specific spectral lines by blood components and the relative intensity of specific wavelengths. The sensor can alternately emit different wavelengths and detect the transmitted or reflected intensity. The sensor can also emit multiple wavelengths simultaneously and a filtered detector measures the intensity of specific wavelengths.

[0062] If the camera 311 detects the presence of a color within the programmed color range, the controller 318 is configured to notify a user, trigger an alarm, or modify operation of the fetal chamber assembly 10. It will be appreciated that because the liquid flowing through the outlet channel 206 may contain a variety of colors, configuring the sensor to focus only on colors associated with the substance being monitored (e.g., meconium or blood) helps to prevent false positives.

[0063] meconium removal Meconium excreted by a fetus into the growth chamber 120 may be removed from the fetal chamber assembly 10 to reduce the risk of infection, bacterial growth, or damage to assembly components. The amount of meconium in the fetal chamber assembly 10 can be estimated by the meconium sensor assembly 292, as described above. Meconium may be visible in the growth chamber 120 and / or the cannula chamber 150. In some embodiments, it is advantageous to remove meconium if the amount of meconium detected by the sensor 310 in the meconium sensor assembly 292 exceeds a predetermined threshold.

[0064] Although it is possible to open the fetal chamber system 10 (e.g., by uncoupling the lid 112 from the base 100) and remove meconium from within the liquid (e.g., PSS) therein, it may be preferable to remove meconium without unlocking and opening the fetal chamber system 10. This helps maintain a controlled environment for the fetus without disturbing the fetus, exposing the fetus or the interior of the fetal chamber assembly 10 to outside contaminants, or pausing operation of the fetal chamber assembly 10 (e.g., pausing the continuous flow of the liquid through the assembly). Thus, in some embodiments, it may be preferable to remove meconium via a dedicated removal port that allows a user to insert a tool into the growth chamber 120 or the cannula chamber 150 and aspirate, scoop, or otherwise remove meconium present in the liquid. As shown in Figures 2-5, the meconium removal assembly 214 may be positioned on the base 100.

[0065] While the above description provides examples of specifically removing meconium from the growth chamber 120, it will be understood that meconium may be present in other portions of the fetal chamber assembly 10, such as the cannula chamber 150, and may be removed from those areas via the disclosed meconium removal assembly 214. In some embodiments, the fetal chamber assembly 10 may include an additional meconium removal assembly 214 advantageously positioned on the fetal chamber assembly 10 to allow access to areas where meconium may be present.

[0066] The meconium sensor assembly 292 is configured to detect a color change indicative of the presence of meconium, as described above. In some embodiments, the meconium sensor assembly 292 may be further configured to detect a color change corresponding to the presence of blood in the fluid passing through the outlet channel 206. The presence of blood in the fluid exiting the growth chamber 120 may indicate fetal bleeding. Blood in the growth chamber 120 or the cannula chamber 150 may indicate a leak between one or more cannulated blood vessels in the umbilical cord and its respective cannula. It is preferable to monitor the presence of blood in the fetal chamber assembly 10 and address such issues before damage to the fetus occurs.

[0067] temperature sensing In addition to blood and meconium, the fetal chamber assembly 10 may be configured to monitor various other parameters of the fluid (e.g., PSS) flowing therethrough. In some embodiments, one or more temperature sensors may be positioned throughout the fetal chamber assembly 10 to measure the temperature of the fluid, components of the fetal chamber assembly 10, or the fetus itself. In some embodiments, the fetal chamber assembly 10 may include multiple temperature sensors strategically positioned throughout the fetal chamber assembly 10 to provide accurate measurements of temperature. As shown in FIGS. 3 and 4, the fetal chamber assembly 10 may include a temperature sensor 280 positioned within the growth chamber 120 to measure the fluid therein. Temperature measurements from some or all of the multiple temperature sensors may be analyzed to calculate an average temperature within the fetal chamber assembly 10, to determine temperature differences in various regions of the fetal chamber assembly 10, to verify the functionality of temperature sensors, and / or to monitor specific regions individually.

[0068] Referring to FIG. 42, an exemplary layout of three temperature sensors 280 is depicted. Although FIG. 42 illustrates three temperature sensors 280, it should be understood that the fetal chamber assembly 10 may be designed with a different number of temperature sensors. For example, one, two, . . . ten, or another suitable number of temperature sensors 280 may be envisioned. Additionally, a "secondary" temperature sensor 280 may be deployed as a redundancy in case one or more of the "primary" temperature sensors 280 become inoperable or defective. The primary and secondary temperature sensors may be substantially the same, the difference being the intended use.

[0069] The temperature sensors 280 may be located in some or all of the fluid flow paths within the growth chamber 120, the cannula chamber 150, and / or the housing 108. The specific location depends on which site the particular temperature sensor 280 is intended to monitor. As shown in FIG. 42, in some embodiments, the fetal chamber assembly 10 may include three temperature sensors 280 located in various areas of the growth chamber 120. For purposes of this disclosure, the three temperature sensors 280 in FIG. 42 are individually labeled as a first temperature sensor 280a, a second temperature sensor 280b, and a third temperature sensor 280c. It will be understood that the first, second, and third temperature sensors 280a-c may be functionally and structurally the same. The first temperature sensor 280 may be located adjacent to the first outlet 194. When a fetus is placed in the growth chamber 120, the first temperature sensor 280 will be closest of the three temperature sensors depicted to the fetus's head. It may be advantageous to have an accurate measurement of the temperature of the liquid in the area of ​​the fetal head. Additionally, the placement of the first temperature sensor 280 adjacent the first inlet 194 may allow for accurate sensing of the temperature of the liquid as it first enters the growth chamber 120.

[0070] The second temperature sensor 280b may be located adjacent the opening 166 between the cannula chamber 150 and the growth chamber 120. The second temperature sensor 280b may be located adjacent the meconium removal port 218. The second temperature sensor 280b may be located at least partially within the growth chamber 120 between the opening 166 and the meconium removal port 218. Such a location may be advantageous as it allows for accurate temperature monitoring immediately downstream of where the liquid from the cannula chamber 150 enters the growth chamber 120 and mixes with the liquid within the growth chamber 120. Monitoring the temperature in this area can ensure that the liquid entering the cannula chamber from the second inlet 198 is of sufficient temperature. In some embodiments, it may be advantageous to monitor the temperature adjacent the meconium removal port 218. During operation, when meconium is removed through the meconium removal port 218, as detailed above, it may be advantageous to monitor the liquid in the immediate vicinity of the meconium removal port 218 to detect temperature changes due to the opening of the port.

[0071] The third temperature sensor 280c may be located adjacent to the outlet 202. The third temperature sensor 280c may be located opposite the first temperature sensor 280a and may be spaced apart from the first temperature sensor 280a along the longitudinal direction y. The third temperature sensor 280c may be located such that the second temperature sensor 280b is located between the first and third temperature sensors 280a, 280c. When a fetus is placed in the growth chamber 120, the third temperature sensor 280c may be the closest of the three temperature sensors to the fetus's feet. It may be advantageous to measure the temperature in the area of ​​the fetus' feet and compare that measurement to the temperature of the fetus's head measured by the first temperature sensor 280a. This may indicate how the temperature of the liquid changes as it flows in a direction from the fetus's head to the fetus's feet. Locating the third temperature sensor 280c adjacent to the outlet 202 may be advantageous to measure the temperature of the liquid as it leaves the growth chamber 120 and compare that measurement to the temperature of the liquid as it enters the growth chamber at the first inlet 194 and / or the opening 166. It will be understood that the particular exemplary arrangement of the three temperature sensors 280a-c is not intended to be limiting and that other arrangements of the temperature sensors 280 and greater or lesser quantities are envisioned. In some embodiments, the temperature sensor 280 may be located within the cannula chamber 150, for example adjacent to the second inlet 198.

[0072] In operation, it is preferred to maintain the temperature of the liquid in the fetal chamber assembly 10 within a preferred temperature range. It will be appreciated that the temperature of the fetal environment may affect the growth and development of the fetus, and that temperatures outside of the preferred range may cause damage to the fetus. Therefore, in some embodiments, it is preferred to maintain the temperature of the liquid in the growth chamber 120 and the cannula chamber 150 at approximately 37.5 degrees Celsius. Temperature variations may be permitted, and the exact preferred temperature may vary depending on the medical requirements associated with the fetus.

[0073] The fetal chamber assembly 10 may be configured to heat or cool the infused liquid to a desired temperature based on temperature measurements from the one or more temperature sensors 280. For example, if an individual or average temperature measurement is below a predetermined threshold, the fetal chamber assembly 10 may be configured to heat the liquid sufficiently to raise the temperature of the liquid to a desired temperature, and conversely, if an individual or average temperature measurement is above a predetermined threshold, the fetal chamber assembly 10 may be configured to cool the liquid sufficiently (or, alternatively, not heat) to lower the temperature of the liquid to a desired temperature.

[0074] In some embodiments, additional temperature sensors (not shown on the fetal chamber assembly 10) may be positioned on the outside of the fetal chamber assembly 10 to measure the temperature of the liquid traveling to the fetal chamber assembly 10. These additional temperature sensors may be used to monitor the temperature of the liquid to ensure that the liquid is heated or cooled to a desired temperature before it is introduced into the fetal chamber assembly 10.

[0075] The fetal chamber assembly 10 may be configured to monitor pressure therein. One or more pressure sensors may be disposed throughout the fetal chamber assembly 10 to measure the pressure of the fluid in the growth chamber 120, the cannula chamber 150, the first inlet 194, the second inlet 198, the outlet 202, the outlet channel 206, or another area of ​​the fetal chamber assembly 10. In some embodiments, the fetal chamber assembly 10 may include multiple pressure sensors strategically positioned throughout the fetal chamber assembly 10 to provide an accurate measurement of pressure. The fetal chamber assembly 10 may be configured to utilize measurements from each of multiple pressure sensors to determine an average pressure calculation. As shown in FIG. 13, the fetal chamber assembly 10 may include a pressure sensor 284 disposed therein.

[0076] 19, an exemplary layout of two pressure sensors 284 is depicted. Although FIG. 19 illustrates two pressure sensors 284, it should be understood that the fetal chamber assembly 10 may be designed with a different number of pressure sensors (e.g., 284a, 284b, etc.). For example, one, two, . . . ten, or another suitable number of pressure sensors 284 may be envisioned. Additionally, a "secondary" pressure sensor 284 may be deployed as a redundancy in case one or more of the "primary" pressure sensors 284 become inoperable or defective. The primary and secondary pressure sensors may be substantially the same, the difference being the intended use.

[0077] With reference to FIG. 13, the fetal chamber assembly 10 may be configured to receive measurements from each pressure sensor 284 and perform calculations based on each individual measurement. The individual measurements may be used to calculate an average pressure within a component of the fetal chamber assembly 10 or a pressure at a particular location relative to the sensor. In some embodiments, the values ​​at each pressure sensor 284 may be used to calculate the pressure at a geometric midpoint of the growth chamber 120 or another preferred area within the growth chamber 120. In some scenarios, it is preferred to continuously monitor the average pressure within the growth chamber 120, especially when a fetus is disposed therein. As shown in FIG. 13, in some embodiments, the fetal chamber assembly 10 may include two pressure sensors 284 positioned around the growth chamber 120 according to a preferred arrangement. For purposes of this disclosure, the two pressure sensors 284 shown in FIG. 13 are individually labeled as a first pressure sensor 284a and a second pressure sensor 284b. It will be understood that the first and second pressure sensors 284a, 284b may be functionally and structurally the same. The use of multiple pressure sensors 284 can advantageously provide pressure measurements of specific regions or zones within the growth chamber 120, and the particular region monitored can depend on the position of the fetus within the growth chamber 120 relative to the separate pressure sensors 284. The pressure within the fetal chamber assembly 10 may be adjusted in response to the monitored pressure based on individual pressure measurements at one or more of the multiple pressure sensors 284 and / or based on calculated pressure values ​​calculated based on the pressure measurements from one or more individual pressure sensors 284.

[0078] In some embodiments, the first and second pressure sensors 284a, 284b may be positioned such that each is substantially equidistant from the physical center of gravity of the growth chamber 120. In some embodiments, the first and second pressure sensors 284a, 284b may be positioned such that each is substantially equidistant from the pitch axis A. Specifically, the first pressure sensor 284a may be positioned adjacent a portion of the growth chamber 120 that receives a fetal head, and the second pressure sensor 284b may be positioned adjacent a portion of the growth chamber 120 that receives a fetal foot. That is, the first pressure sensor 284a may be closer to the fetal head than the fetal foot. The second pressure sensor 284b may be closer to the fetal foot than the fetal head.

[0079] The fetal chamber assembly 10 may be configured to notify a user, activate an alarm, and / or modify its position or movement if the measured pressure is outside of a predetermined range. In some embodiments, it may be preferable to maintain the pressure in the growth chamber 120 (calculated at the center of gravity of the growth chamber) between about 4 mmHg and about 6 mmHg. It will be appreciated that other suitable pressure ranges may be utilized and will depend on the parameters of the fetal chamber assembly 10 and the fetus.

[0080] Pressure Relief Device In some embodiments, gas may become trapped within the fetal chamber assembly 10 during fetal loading, the cannulation process, meconium removal, or during movement of the fetal chamber assembly 10. The gas may include air and may include a general mixture of atmospheric gases. In some embodiments, air may seep into the interior of the fetal chamber assembly 10 at one or more of the ports described throughout this application. Additionally, dissolved gas in the liquid being moved to and through the fetal chamber assembly 10 may separate from the liquid. During operation of the fetal chamber assembly 10, gas may escape from the fetus during the normal pregnancy process and enter the environment immediately adjacent to the fetus (i.e., the liquid surrounding the fetus in the growth chamber 120). The air (or other gas) may be disposed in gaseous form between the base 100 and the lid 112. In some embodiments, pockets of air may form within the growth chamber 120 and / or the cannula chamber 150.

[0081] Air present in the growth chamber 120 and / or the cannula chamber 150 may be harmful to a fetus. In some embodiments, the presence of air may interfere with desired imaging of a fetus during pregnancy. For example, air may interfere with ultrasound imaging of a fetus in the growth chamber 120. In some embodiments, the presence of air may lead to drying out of assembly components, tubing, cannula, etc. This may result in physical cracking or breakage of components and may result in leaks in the fetal chamber assembly 10. It is preferable to keep the fetus and its umbilical cord submerged in liquid throughout the pregnancy. If any part of the fetus or umbilical cord comes into contact with the gas, the fetus or umbilical cord may become desiccated or otherwise be damaged. Additionally, the gas trapped within the fetal chamber assembly 10 may be non-sterile and may contain contaminants, viruses, bacteria, or other impurities that are undesirable within the fetal chamber assembly 10.

[0082] It may be preferable to remove at least a portion of the air trapped within the fetal chamber assembly 10. The fetal chamber assembly 10 may include a pressure relief component configured to reduce pressure within the growth chamber 120. With reference to FIG. 16, the air may be removed from the growth chamber 120 and / or the cannula chamber 150 through one or more air removal ports 260 disposed on the fetal chamber assembly 10 (see generally, FIGS. 2 and 16). With reference to FIG. 2, the air removal port 260 may be disposed on the base 100 or on the lid 112. The air removal port 260 may be a pressure relief component. In some embodiments, the air removal port 260 may be disposed on a cannula chamber membrane 308 (as shown in FIG. 2). In some embodiments, the air removal port 260 may be disposed on the top membrane 124 of the growth chamber 120. In some further embodiments, the air removal port 260 may be disposed on the housing 108 of the base 100 (see also FIG. 2). In some aspects, the fetal chamber assembly 10 may include a plurality of the air removal ports 260 disposed throughout the fetal chamber assembly 10. In certain embodiments, the air removal ports 260 may be used to remove fluids (e.g., gases or liquids such as PSS).

[0083] Each air port 260 defines a passageway extending therethrough that fluidly communicates between the interior space 104 (i.e., the space between the base 100 and the lid 112) or growth chamber of the fetal chamber assembly 10 and the environment external to the fetal chamber assembly 10. Because the liquid flowed through the fetal chamber assembly 10 is heavier and denser than air, the liquid (e.g., PSS) will naturally fall (by gravity) downward, displacing air such that the air is located relatively above the liquid ("above" being measured from the liquid in a direction against gravity). Due to the geometry of the components of the fetal chamber assembly 10, air bubbles that form may become trapped in areas of the fetal chamber assembly 10 that do not include the air removal port 260. As such, it may be preferable to move the fetal chamber assembly 10 so that trapped air bubbles are directed toward one or more of the air removal ports 260. As previously described, the fetal chamber assembly 10 may be rotated along the pitch, roll, and yaw axes. In operation, a user can rotate the fetal chamber assembly 10 along one, two, or all three of the pitch, roll, and yaw axes to direct trapped air bubbles toward the desired air removal port 260. In some exemplary embodiments, the fetal chamber assembly 10 can be rotated up to about 45 degrees (measured from the horizontal-vertical plane defined above) along the roll axis such that air trapped between the base 100 and the lid 112 is displaced toward the air removal port 260 located on the cannula chamber membrane 308. As the air is displaced adjacent the air removal port 260, it can flow out of the fetal chamber assembly 10 through the air removal port 260.

[0084] In some embodiments, a user can deform, push, or palpate the top membrane 124 or the cannula chamber membrane 308 to direct the air in a desired direction toward the air removal port 260. In some embodiments, the air removal port 260 may be located on the housing 108. For example, the air removal port 260 may be located adjacent to the meconium removal port 218. Referring to FIG. 18, an exemplary arrangement of the fetal chamber assembly 10 is depicted. The fetal chamber assembly 10 is shown rotated to a desired angle along the roll axis. The air bubble 380 is seen to be located adjacent to the air removal port 260. Liquid 382 is shown below the air bubble 380 ("below" being relative to the vertical direction of gravity). A user 384 is shown applying a force to the top membrane 124. This force and the relative position of the fetal chamber assembly 10 may cause the air bubble 380 to move towards the air removal port 260 where the air may be expelled from the fetal chamber assembly 10 .

[0085] The air removal port 260 may be configured to receive an air removal assembly 264 therein. The air removal assembly 264 allows the air removal port 260 to be selectively opened and closed such that air may pass or be prevented from passing, respectively. With reference to FIGS. 16-17, an exemplary air removal assembly 264 is depicted engaged with an exemplary air removal port 260. It will be understood that other similar devices may be utilized. The air removal port 260 includes a passageway 262 extending therethrough that is in fluid communication with both the interior surface 104 and an environment external to the fetal chamber assembly 10. The air removal port 260 is configured to receive the air removal assembly 264 in the passageway 262. The air removal assembly 264 defines a passageway 266 extending therethrough. The passageway 266 is configured to be in fluid communication with the passageway 262. When the air removal assembly 264 is engaged with the air removal port 260, the passageway 266 is in fluid communication with the interior space 104 and the environment outside the fetal chamber assembly 10. The air removal assembly 264 may include a clamp 268 configured to selectively block or unblock the passageway 266. It will be appreciated that the material of the air removal assembly 264 should be sufficiently deformable that it may be compressed by the clamp 268 and sufficiently resilient to return to an uncompressed position when the clamp 268 is opened. The air removal assembly 264 may be comprised of plastic or silicone tubing. The air removal assembly 264 may further include a check valve 270 configured to allow air or liquid to pass therethrough in one direction (e.g., out of the fetal chamber assembly 10) while preventing the passage of material in the opposite direction (e.g., into the fetal chamber assembly 10). A vent cap 272 may be positioned on the air removal assembly 264 to allow air to escape from the air removal assembly 264 through the passageway 266 while preventing the ingress of external contaminants or debris into the passageway 266 .A lid 272 may be removably coupled to the air removal assembly 264 such that a user can selectively open and close the lid 272 to remove air. In some embodiments, the lid 272 may be threadably connected to the air removal assembly 264. In some embodiments, the lid 272 may include a hydrophobic filter that allows gas to pass but not liquids.

[0086] The disclosed systems and devices may be configured for use with fetuses, including term and preterm fetuses. A preterm fetus may be a preterm fetus (e.g., less than 37 weeks estimated gestation, particularly 28-32 weeks estimated gestation), a very preterm fetus (24-28 weeks estimated gestation), or a precursor fetus (20-24 weeks estimated gestation). The gestational ages are for humans, but preterm fetuses from other animals may be used. In some embodiments, the preterm fetus may not have an underlying congenital disease. In other embodiments, the fetus may have limited capacity for pulmonary gas exchange due to congenital anomalies that affect lung development, such as, for example, pulmonary hypoplasia or congenital diaphragmatic hernia. The disclosed systems may be configured to maintain the fetus within the system for as long as necessary (e.g., days, weeks, or months) until the fetus is able to live without the system. The particular size, shape, and dimensions of the disclosed fetal chamber assembly 10 will depend on the intended use, the size of the fetus, and manufacturing constraints. In some exemplary embodiments, the fetal chamber assembly 10 can have a first dimension measured along a longitudinal direction y of between about 10 inches and about 24 inches, between about 14 inches and about 220 inches, or another suitable range. The fetal chamber assembly 10 can have a second dimension measured along a transverse direction x of between about 8 inches and about 22 inches, between about 12 inches and about 18 inches, or another suitable range. The fetal chamber assembly 10 can have a third dimension measured along a longitudinal direction y of between about 2 inches and about 12 inches, between about 4 inches and about 10 inches, or another suitable range.

[0087] PSS Circuit 19, the PSS can flow through a PSS circuit 500. The PSS circuit 500 can be configured to introduce the PSS into the growth chamber 120. The PSS circuit 500 can include conduits that fluidly connect elements of the PSS circuit 500 to one another. The PSS circuit 500 can include a container 502. In some examples, the container 502 includes the PSS. In other examples, the container 502 includes a substance and an aqueous solvent is passed through the container to generate the PSS as described above. The container 502 can be in fluid communication with a valve 504. In some examples, the valve 504 is manually operable. In other examples, the valve 504 is coupled to a controller. The controller can be configured to send a signal to the valve to open or close the valve. The valve 504 can be configured to allow the PSS to flow through the valve 504 when the valve 504 is open. The valve 504 can prevent the flow of the PSS when the valve 504 is closed. The valve 504 may be fluidly coupled to a pump 506. The pump 506 may be a feed pump. The feed pump 506 may be configured to move the PSS from the vessel 502 to the growth chamber 120. The feed pump 506 may be configured to regulate the flow of the PSS into the growth chamber 120. The PSS circuit 500 may include an integrated heat exchanger configured to regulate a temperature of the PSS in the vessel 502. The heat exchanger may be configured to heat the PSS in the vessel 502.

[0088] The vessel 502 can be a first vessel. The PSS circuit 500 can include a second vessel 508. The PSS circuit 500 can include a conduit fluidly coupling the vessels 502, 508 to the growth chamber 120. In some examples, the second vessel 508 includes the PSS. In other examples, the second vessel 508 includes a substance, and an aqueous solvent is passed through the vessel to produce the PSS, as previously described. The second vessel 508 can be in fluid communication with a second valve 510. In some examples, the second valve 510 is manually operable. In other examples, the second valve 510 is coupled to the controller. The second valve 510 can be configured to allow the PSS to flow through the second valve 510 when the second valve 510 is open. The second valve 510 can prevent the flow of the PSS when the second valve 510 is closed. The second valve 510 can be fluidly coupled to the pump 506. The first and second valves 504, 510 may be independently operable to allow one of the first and second vessels 502, 508 to be replaced without interrupting operation of the PSS circuit 500. In some examples, the first and second vessels 502, 508 contain the same material (e.g., the PSS). In other examples, the first and second vessels 502, 508 contain different materials that are combined by the PSS circuit 500. The PSS circuit 500 can include an integrated heat exchanger configured to regulate the temperature of the PSS in the vessel 508. The heat exchanger can be configured to heat the PSS in the vessel 508.

[0089] The PSS circuit 500 can be configured to detect the volume of material in the first and second containers 502, 508. The PSS circuit 500 can include a sensor (e.g., weight sensor, optical sensor) configured to sense the volume of the material in the first and second containers 502, 508. The PSS circuit 500 can be configured to draw from one of the first and second containers 502, 508 until a selected threshold is reached. The threshold can be a minimum weight or a minimum volume. The PSS circuit 500 can be configured to close one of the first and second valves 504, 510 and open the other of the first and second valves 504, 510 when the volume of the material in the first and second containers 502, 508 is equal to or less than the selected threshold. In some examples, the controller sends first and second signals to open and close the first and second valves 504, 510. In another example, the PSS circuit 500 generates an observable signal (e.g., sound or light) to notify a user or medical professional that one of the first and second containers 502, 508 is at or below the selected threshold.

[0090] The pump 506 can be coupled to a sensor 512. In one particular embodiment, the pump 506 is a peristaltic pump. The sensor 512 is a pressure sensor. The sensor 512 can be configured to detect pressure within the PSS circuit 500. The sensor 512 can be configured to send a sensor signal indicative of a pressure level to the controller. The controller can be configured to compare the sensor signal to a threshold level. The controller can be configured to stop the pump 506 if the pressure level exceeds the threshold level.

[0091] The PSS circuit 500 can include a sterilizer 514 configured to sterilize the PSS as it flows toward the growth chamber 120. In some examples, the sterilizer 514 includes an ultraviolet (UV) light source configured to sterilize the PSS. A conduit can be elongated along a central axis of the conduit. The sterilizer 514 can be positioned at an angle relative to the central axis of the conduit to prevent light from traveling through the conduit to the growth chamber 120. The sterilizer 514 can emit light at an angle of about 60 degrees to about 120 degrees, about 70 degrees to about 11 degrees, about 80 degrees to about 100 degrees, or about 90 degrees relative to the central axis of the conduit. The light source can be a light emitting diode (LED). The sterilizer 514 can include a plurality of UV LEDs. The pre-sterilizer 514 can be configured to emit light having a wavelength of about 260 to about 280 nanometers. In some examples, the sterilizer 514 includes a radio frequency emitter configured to sterilize the PSS. The sterilizer 514 can emit radio frequency to heat the PSS, thereby sterilizing the PSS. The sterilizer 514 can be configured to sterilize the PSS without contacting the PSS.

[0092] The PSS can flow through the filter 516. The filter 516 can be configured to remove particles from the PSS. The filter 516 can be configured to remove particles above a threshold size. The filter 516 can be removably coupled to the PSS circuit. The filter 516 may be removable to replace the filter 516. The sensor 512 can be located upstream of the filter 516. The sensor 512 can detect a pressure increase indicative of particulate buildup on the filter 516. In one embodiment, the PSS systems described herein employ multiple filters to allow replacement of any one or more filters without disturbing other filters in the system.

[0093] The sensor 512 may be a first sensor. The PSS circuit 500 may include a second sensor 518. The second sensor 518 may be a pressure sensor. The first sensor 512 may be upstream from the filter 516. The second sensor 518 may be downstream from the filter 516. The second sensor 518 may be configured to detect pressure in the PSS circuit 500. The second sensor 518 may be configured to send a sensor signal indicative of the pressure level to the controller. The controller may be configured to compare the signal from the first sensor 512 and the signal from the second sensor 518. The controller may determine if the filter 516 is clogged by comparing the signals from the first and second sensors 512, 518. The controller may be configured to compare the sensor signal from the second sensor 518 to the threshold. The controller may be configured to stop the pump 506 if the pressure level exceeds the threshold level.

[0094] The PSS circuit 500 can include a third sensor 520. The third sensor 520 can be a flow sensor. The third sensor 520 can be configured to send a signal that causes an increase or decrease in PSS flow rate from the pump 506. The third sensor 520 can be configured to send a signal directly to the pump 506. In other examples, the third sensor 520 is configured to send a signal to the controller, which sends a signal to the pump 506 in response to receiving the signal from the third sensor 520.

[0095] The PSS circuit 500 may include a heat exchanger 522. The heat exchanger 522 may be configured to heat the PSS flowing through the PSS circuit 500. Alternatively, the heat exchanger 522 may be configured to cool the PSS flowing through the PSS circuit 500. The heat exchanger 522 may be configured to receive a signal from one or more temperature sensors 280 to adjust the temperature of the PSS as needed. The one or more temperature sensors 280 may be configured to send a signal to the controller. The controller may be configured to send a signal to the heat exchanger 522 in response to receiving the signal from the one or more temperature sensors 280. The heat exchanger 522 may be actuated in response to a temperature sensed by the one or more temperature sensors 280. The heat exchanger 522 may include a heated liquid body, with the PSS flowing in a conduit through the heated liquid body to heat the PSS.

[0096] The PSS circuit 500 can include a third valve 524. The third valve 524 can be a diversion valve. The third valve 524 can divert the flow of the PSS from a first path to a second path. The first path can allow the PSS to flow from the heat exchanger 522 to a fourth sensor 526. The second path can allow the PSS to flow from the heat exchanger 522 through the second filter 528 to waste or atmosphere to relieve pressure in the system. In some examples, the PSS flows through each of the first filter 5166 and the second filter 528 during normal operation of the PSS circuit 500. In other examples, the PSS flows through only one of the first and second filters 516, 528 during normal operation of the PSS circuit 500. A system with one filter can ensure that the PSS is always filtered, even when one of the first and second filters 516, 528 is removed for cleaning or replacement.

[0097] The fourth sensor 526 can be a pressure sensor. The second sensor 518 can be upstream from the second filter 528. The fourth sensor 526 can be downstream from the second filter 528. The fourth sensor 526 can be configured to detect pressure in the PSS circuit 500. The fourth sensor 526 can be configured to send a sensor signal indicative of the pressure level to the controller. The controller can be configured to compare the sensor signal to a threshold level. The controller can be configured to deactivate or otherwise adjust the PSS flow rate from the pump 506 if the pressure level exceeds the threshold level. The fourth sensor 526 can be configured to send a signal indicative of the pressure level at the fourth sensor 526 to the controller. The controller can be configured to compare the signal from the second sensor 518 to the signal from the fourth sensor 526. By comparing the signals from the second and fourth sensors 518, 526, the controller can determine if the second filter 528 is clogged.

[0098] The PSS circuit 500 can include a third filter 530. In one particular embodiment, the third filter 530 is a bubble filter. The third filter 530 can be downstream from each of the first and second filters 512, 528. In one particular embodiment, at least one of the first and second filters 512, 528 can be a media filter, and the third filter 530 can be a bubble filter.

[0099] The PSS system of FIG. 19 includes a plurality of sterilizers. In certain embodiments of the system, any one or more of the sterilizers are comprised of a UV light, a UV light emitting diode ("LED"), or a radio frequency sterilizer. The sterilizer 514 may be a first sterilizer. The PSS circuit 500 may include a second sterilizer 532. The second sterilizer 532 may be fluidly coupled to a third filter 530. The second sterilizer 532 may be configured to sterilize the PSS as it flows toward the growth chamber 120. In some embodiments, the second sterilizer 532 includes a UV light source configured to sterilize the PSS. The light source may be an LED. The second sterilizer 532 may include a plurality of UV LEDs. The second sterilizer 532 may be configured to emit light having a wavelength of about 260 to about 280 nanometers. The second sterilizer 532 may be positioned at an oblique angle relative to the central axis of the conduit to prevent light from traveling through the conduit to the growth chamber 120. The second sterilizer 532 may emit light at an angle of about 60 degrees to about 120 degrees, about 70 degrees to about 110 degrees, about 80 degrees to about 100 degrees, or about 90 degrees relative to the central axis of the conduit. In some embodiments, the second sterilizer 532 includes a radio frequency emitter configured to sterilize the PSS. The second sterilizer 532 may emit radio frequency to heat the PSS, thereby sterilizing the PSS. The second sterilizer 532 may be configured to sterilize the PSS without contacting the PSS. In one embodiment, the PSS system described herein employs multiple sterilizers to allow replacement of any one or more sterilizers without disturbing other sterilizers in the system.

[0100] The PSS circuit 500 can include a fifth sensor 534. The fifth sensor 534 can be a temperature sensor. The fifth sensor 534 can be fluidly coupled to the sterilizer 532. The fifth sensor 534 can be a plurality of sensors that measure temperature along the PSS circuit. The fifth sensor 534 can measure the temperature of the PSS as it enters the growth chamber 120. In one embodiment, the temperature of the PSS in the growth chamber 120 is in the range of about 37 to about 38 degrees Celsius.

[0101] The PSS can flow from the fifth sensor 534 to the growth chamber 120. The PSS can flow from the growth chamber 120 to the third sterilizer 536. The third sterilizer 536 can be fluidly coupled to the growth chamber 120. The third sterilizer 536 can be configured to sterilize the PSS as it flows from the growth chamber 120. Sterilizing the PSS after it exits the growth chamber 120 can allow the PSS to be disposed of down a drain. The drain can be a municipal sewer system. In some embodiments, the third sterilizer 536 includes a UV light source configured to sterilize the PSS. The light source can be an LED. The third sterilizer 536 can include a plurality of UV LEDs. The third sterilizer 536 can be configured to emit light having a wavelength of about 260 to about 280 nanometers. The third sterilizer 536 may be positioned at an oblique angle relative to the central axis of the conduit to prevent light from traveling through the conduit to the growth chamber 120. The third sterilizer 536 may emit light at an angle of about 60 degrees to about 120 degrees, about 70 degrees to about 110 degrees, about 80 degrees to about 100 degrees, or about 90 degrees relative to the central axis of the conduit. In some embodiments, the third sterilizer 536 includes a radio frequency emitter configured to sterilize the PSS. The third sterilizer 536 may emit radio frequency to heat the PSS, thereby sterilizing the PSS. The third sterilizer 536 may be configured to sterilize the PSS without contacting the PSS. The third sterilizer 536 may sterilize the PSS after it leaves the growth chamber 120 so that the PSS can be circulated through the PSS circuit 500 again. The third sterilizer 536 can sterilize the PSS after it exits the growth chamber 120 such that the PSS may be circulated through the PSS circuit 500 again, with or without the addition of additional PSS.

[0102] The PSS circuit 500 may include a second pump 538. The second pump 538 may be fluidly coupled to the third sterilizer 536. The second pump 538 may be a waste pump that pumps the PSS to a waste container or drain. The second pump 538 may be configured to pump the PSS from the growth chamber 120. The pressure sensor 284a, 284b of the fetal chamber assembly 19 may be configured to send a signal to control the second pump 538. In some examples, the pressure sensor 284a, 284b sends a signal directly to the second pump 538. In other examples, the pressure sensor 284a, 284b sends a signal to the controller, which sends the signal to the second pump 538 in response to receiving a signal from the pressure sensor 284a, 284b. The second pump 538 can regulate the pressure in the growth chamber 120, at least in part, by adjusting or stopping the flow of the PSS out of the growth chamber 120. In certain embodiments, the pressure sensors 284a, 284b maintain the pressure in the growth chamber 120 in a range of about 4 to about 6 mmHg. The second pump 538 can be a first pressure release configured to reduce the pressure in the growth chamber 120. A pressure release element, described below, can be a second pressure release configured to reduce the pressure in the growth chamber 120. The first pressure release can be operable independently of the second pressure release. The height of the PSS outlet in the growth chamber 120 can be selected to at least in part control the pressure in the growth chamber 120.

[0103] In certain embodiments, at least a portion of the PSS exiting the growth chamber 120 is analyzed for contaminants, such as, but not limited to, bacteria. If analysis of the PSS detects a contaminant, the flow rate of the PSS through the growth chamber 120 is increased to eliminate or substantially reduce the presence of the contaminant through the system to a safe level.

[0104] The PSS circuit 500 can include a third container 540. The third container 540 can be a waste container. The third container 540 can be configured to receive the PSS. The third container 540 can be configured to receive the PSS after the PSS exits the growth chamber 120. The third container 540 can be fluidly coupled to the second pump 538. A fourth valve 544 can prevent or allow the flow of the PSS from the second pump 538 to the third container 540. In some embodiments, the fourth valve 544 is manually operable. In other embodiments, the fourth valve 544 is coupled to the controller. The controller can be configured to send a signal to the fourth valve 544 to open or close the fourth valve 544. The fourth valve 544 can be configured to allow the PSS to flow through the fourth valve 544 when the fourth valve 544 is open. The fourth valve 544 may prevent the flow when the fourth valve 544 is closed.

[0105] The PSS circuit 500 can include a fourth container 542. The fourth container 542 can be a waste container. In other examples, the PSS can be received in the fourth container 542, which can be removed and coupled to the first valve 504 so that the PSS can be recycled through the PSS circuit 500. In other examples, the fourth container 542 is a drain. The drain can be coupled to a sewer system. The fourth container 542 can be configured to receive the PSS. The fourth container 542 can be fluidly coupled to the second pump 538. A fifth valve 546 can prevent or allow the flow of the PSS from the second pump 538 to the fourth container 542. In some examples, the fifth valve 546 is manually operable. In other examples, the fifth valve 546 is coupled to the controller. The controller can be configured to send a signal to the fifth valve 546 to open or close the fifth valve 546. The fifth valve 546 can be configured to allow the PSS to flow through the fifth valve 556 when the fifth valve 546 is open. The fifth valve 546 can prevent the flow when the fifth valve 546 is closed.

[0106] 20, at least one of the first, second, third, and fourth containers 502, 508, 540, and 542 can be a container 600. The container 600 can include an outer wall 602 defining an internal cavity. The container 600 can be a bag. The PSS can be stored within the internal cavity. The container 6000 can include a mating element 604. The mating element 604 can be configured to mate with a corresponding mating element on the fetal chamber 10 such that the container 600 is coupled to the fetal chamber 10. The mating element 604 can be an opening that receives a protrusion. In other examples, the mating element 604 can be a hook, a protrusion, or an adhesive.

[0107] The container 600 may include an inlet 606. The PSS may be introduced into the internal cavity through the inlet 606. The inlet 606 may include a conduit 608 coupled to the body 602 such that the PSS may flow through the conduit 608 and into the internal cavity. The inlet 606 may include a stopper 610 configured to prevent the flow of the PSS through the conduit 608. The stopper 610 may be a clamp. The inlet 606 may include a lid 612. The lid 612 may be removably coupled to the conduit 608. The lid 612 may prevent the flow of the PSS through the conduit 608 when the lid 612 is coupled to the conduit 608. The conduit 608 may be configured to be removably coupled to a PSS source for introducing the PSS into the internal cavity. In some embodiments, the conduit 608 is fluidly coupled to one of the fourth and fifth valves 544 , 546 of the PSS circuit 500 .

[0108] The vessel 600 can include the outlet 614. The PSS can exit the internal cavity through the outlet 614. The outlet 614 can include an outlet conduit 616. The outlet conduit 616 can be coupled to the body 602 such that the PSS can flow from the internal cavity through the outlet conduit 616. The outlet conduit 616 can be configured to couple to one of the first and second valves 504, 510 of the PSS circuit 500. The outlet conduit 616 can be configured to be removably coupled to the PSS circuit 500. In some embodiments, the PSS can be transferred from the vessel 600 to the growth chamber 120 without diluting the PSS. The outlet 614 can include the lid 618. The lid 618 can be removably coupled to the outlet conduit 616. The lid 618 can prevent the flow of the PSS through the outlet conduit 616 when the lid 618 is coupled to the outlet conduit 616. The outlet 614 can include a seal 620 for forming a fluid-tight seal between the outlet conduit 616 and the PSS circuit 500. The seal 620 can be an O-ring. The outlet 614 can include the outlet stopper 622. The outlet stopper 622 can be a clamp. The outlet stopper 622 can be removably coupled to the outlet conduit 616. The lid 618 and the outlet stopper 622 can each prevent the flow of the PSS through the outlet conduit 616.

Claims

1. Physiological saline solution, an aqueous solvent; about 3.0 mM to about 5.0 mM potassium chloride; about 15.0 mM to about 20 mM sodium bicarbonate; about 90 mM to about 110 mM sodium chloride; about 9 mM to about 13 mM sodium acetate; and the saline solution has a pH in the range of about 7.0 to about 7.4; The saline solution optionally contains about 1.0 mM to about 2.0 mM calcium chloride. Saline solution.

2. 10. The saline solution of claim 1, wherein the saline solution has an osmolality ranging from about 250 mOsm to about 270 mOsm.

3. 3. The physiological saline solution according to claim 1, further comprising at least one additive selected from the group consisting of growth factors, antimicrobial peptides, and combinations thereof.

4. 4. The saline solution of claim 3, wherein the growth factor is selected from the group consisting of insulin-like growth factor 1, insulin-like growth factor 2, epidermal growth factor, hepatocyte growth factor, transforming growth factor alpha, and transforming growth factor beta-1, and combinations thereof.

5. The saline solution of claim 4, wherein the antimicrobial peptide is selected from the group consisting of human alpha defensin 1-3, human beta defensin-1, human beta defensin-2, human beta defensin-3, human beta defensin-4, bactericidal / permeability increasing protein, lactoferrin, cathelicidin, calprotectin, and combinations thereof.

6. The physiological saline solution according to claim 1, further comprising: Physiological saline, which has a buffering agent.

7. 7. A saline solution according to any one of claims 1 to 6, comprising an airtight container having an internal volume.

8. 1. A method for preparing a saline solution, comprising: dissolving sodium chloride in an aqueous solvent; dissolving sodium bicarbonate in the aqueous solvent; dissolving potassium chloride in the aqueous solvent; adding a pH adjusting substance comprising sodium acetate to said aqueous solvent in an amount sufficient to adjust the pH to a value of about 7.0 to about 7.4 to provide said saline solution; and The method optionally comprises dissolving calcium chloride in the aqueous solvent. method.

9. The method of claim 8 further comprising: The method comprising the step of introducing an additive selected from a growth factor, an antimicrobial peptide, or a combination thereof into the aqueous solvent.

10. 10. The method according to claim 8, wherein the saline solution is about 3.0 mM to about 5.0 mM potassium chloride; about 15.0 mM to about 20 mM sodium bicarbonate; about 90 mM to about 110 mM sodium chloride; about 9 mM to about 13 mM sodium acetate; optionally about 1.0 mM to about 2.0 mM calcium chloride; The method of claim 1,

11. 11. The method of any one of claims 8 to 10, wherein the saline has an osmolality in the range of about 250 mOsm to about 270 mOsm.

12. 12. The method according to claim 8, wherein the step of adding a pH adjusting substance further comprises: adding hydrochloric acid to the aqueous solvent.

13. 10. The method of claim 9, wherein the growth factor is selected from the group consisting of insulin-like growth factor 1, insulin-like growth factor 2, epidermal growth factor, hepatocyte growth factor, and combinations thereof.

14. 10. The method of claim 9, wherein the antimicrobial peptide is selected from the group consisting of human beta defensin-1, human beta defensin-2, human beta defensin-3, human beta defensin-4, bactericidal / permeability increasing protein, calprotectin, and combinations thereof.

15. 15. The method of any one of claims 8 to 14, further comprising: storing the saline solution in a sealed container.

16. 1. A saline circulation system comprising: a saline supply; a conduit configured to fluidly connect the saline supply to a fetal chamber; a pump coupled to the conduit, the pump configured to pump the saline from the saline supply to the fetal chamber; a filter coupled to the conduit configured to filter the saline as it is pumped from the saline supply to the fetal chamber; A saline circulation system having:

17. 17. The saline circulation system of claim 16, wherein the filter is a first filter, the system further comprising: a second filter in fluid communication with the conduit, each of the first and second filters configured to filter the saline as it flows from the source toward the fetal chamber.

18. 20. The saline circulation system of claim 17, wherein one of the first filter and the second filter is configured to be replaced while the saline flows through the other of the first filter and the second filter.

19. The physiological saline circulation system according to any one of claims 16 to 18, further comprising: a pressure sensor configured to sense pressure within the conduit.

20. The physiological saline circulation system according to any one of claims 16 to 19, further comprising: A saline circulation system comprising a sterilizer configured to sterilize the saline.

21. 21. The saline circulation system of claim 20, wherein the sterilizer is a first sterilizer and is configured to be positioned upstream from the fetal chamber; A saline circulation system, the system including a second sterilizer configured to be positioned downstream from the fetal chamber, the second sterilizer configured to sterilize the saline.

22. 21. The saline circulation system of claim 20, wherein the sterilizer comprises an ultraviolet (UV) light source.

23. 23. The saline circulation system of claim 22, wherein the conduit is elongated along a central conduit axis, and the sterilizer is configured to emit the ultraviolet light along a central light axis that is positioned at an oblique angle relative to the central conduit axis to prevent the ultraviolet light from traveling through the conduit and into the fetal chamber.

24. 24. The saline circulation system of claim 23, wherein the angle is approximately 90 degrees.

25. 21. The saline circulation system of claim 20, wherein the sterilizer is configured to emit radio frequency waves to sterilize the saline.

26. 21. The saline circulation system of claim 20, wherein the sterilizer is configured to emit radio frequency waves to heat the saline.

27. 27. The saline circulation system according to any one of claims 16 to 26, further comprising: A saline circulation system comprising a heat exchanger configured to heat the saline.

28. 28. The physiological saline circulation system according to any one of claims 16 to 27, further comprising: A saline circulation system comprising a pressure relief valve coupled to the conduit.

29. 29. The saline circulation system of any one of claims 16 to 28, wherein the pump is a first pump, and the system further comprises: a second pump coupled to the conduit, the second pump configured to pump the saline from the fetal chamber to a waste container.

30. 30. The saline circulation system of claim 29, wherein the first pump is positioned upstream of the fetal chamber and the second pump is positioned downstream of the fetal chamber.

31. The saline circulation system according to any one of claims 16 to 30, further comprising: A saline circulation system comprising a temperature sensor coupled to the conduit, the temperature sensor configured to sense a temperature of the saline.

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