EP4663177A1

EP4663177A1 - Chamber system for mammalian fetal development and maturation

Info

Publication number: EP4663177A1
Application number: EP24382637.7A
Authority: EP
Inventors: Eduardo Gratacos Solsona; Elisenda EIXARCH ROCA; Elisenda BONET CARNÉ; Miriam Illa Armengol; Yolanda Jacoba de Roo Puente
Original assignee: Universitat de Barcelona UB; Hospital Sant Joan de Deu; Hospital Clinic de Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer
Current assignee: Universitat de Barcelona UB; Hospital Sant Joan de Deu; Hospital Clinic de Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer
Priority date: 2024-06-12
Filing date: 2024-06-12
Publication date: 2025-12-17
Also published as: WO2025257344A1

Abstract

The present invention refers to a system for maturing a premature mammalian fetus. The system comprises a fetal chamber and an amniotic fluid circuit. The fetal chamber comprises a first section, a second section and a connection area. The first section comprises a first rigid frame, an elastic film comprising at least one fluid inlet port; and a first sealing means. The second section comprises a second rigid frame, a fetal bed comprising at least one fluid outlet port and a second sealing means. The connection area comprises at least one opening. The first and second sections have an open position and a closed position. The amniotic fluid circuit is configured to provide an amniotic fluid to and from the fetal chamber and to sterilise the amniotic fluid. The system maintains asepsis, facilitates transfer from the mother's uterus, allows a certain degree of movements and prevents skin damage and ulcers.

Description

Technical field of the invention

The present invention belongs to the fields of medicine and veterinary. Particularly, the present invention relates to the field of neonatal care, more specifically to a system for the maintenance of homeostasis in the premature fetus outside of the womb.

Background of the invention

In cases of extreme prematurity, the survival of the fetus outside the womb is severely challenged by inadequate organ development, particularly the insufficient growth and maturation of the lungs required for effective gas exchange.
Therefore, in extreme-premature fetus, traditional incubators are not sufficient and further extracorporeal systems capable of supporting fetal growth and development, without the disruptions associated with postnatal intensive care have been developed.
While these systems can temporarily replicate the environment of the maternal womb, they face enormous challenges into maintaining such conditions for long periods of time, such that the fetus can continue growing and developing until viable for delivery. Main challenges of these systems entail (1) maintaining asepsis in a system which replicates an ideal environment for bacterial and viral growth promotion: heat, humidity and a protein-rich environment, (2) facilitating an easy transfer from the maternal uterus to the system, (3) allowing certain degree of fetal movements, necessary for the normal development of the fetus, while protecting from accidents due to said movements the point of connection of the fetal umbilical cord with the vascular cannulas that connect the fetus to an extracorporeal circulation, which can potentially damage irreversibly the system, and (4) avoiding skin damage and ulcers produced by sustained contact of certain parts of the fetus body with the container.
In order to replicate the amniotic fluid, many of these extracorporeal systems rely on artificial or biomimetic alternatives to this amniotic fluid. To prevent the development of bacteria and viruses, current solutions rely on replacing this fluid on a continuous basis. However, this is not only expensive, but it has environmental consequences and it is not fully replicating the natural cycle of the amniotic fluid, which its absorbed by osmosis first and by the fetal gut later, while being enriched by both maternal plasma and fetal urine first and meconium later. There is therefore a need for:

(1) An extracorporeal system for the maintenance of homeostasis in the premature fetus outside of the womb that can prevent and treat the development of bacteria and viruses in a more environmentally friendly and biomimetic way.
(2) Solutions that allow approaching part of the system, specifically the "fetal bed", i.e. the specific receptacle where the fetus is physically placed, to the operating area. This allows that the fetus be transitioned smoothly from the maternal uterus to the system. To this end, there is a need for the system to have an articulate configuration that makes possible disassembling one part (the fetal bed) to receive the fetus, and then, once the fetus is positioned, transport and assemble the fetal bed into the full system.
(3) To integrate in the design of the system parts that protect physically the umbilical cord connection, so that the possibility of cord accidents is minimized.
(4) To combine in the design of the fetal bed some areas with enough stiffness to ensure containment of the fetus, but other areas with extra elasticity that mimics the mammalian uterus and allows fetal movements, particularly limb extensions, while preventing too pronounced movements that can risk the vascular connections in the cord and precenting also the appearance of ulcers in contact points of the fetus with the bed.

Summary of the invention

The present invention refers to a system for maturing a premature mammalian fetus. The system comprises a fetal chamber and an amniotic fluid circuit. The fetal chamber comprises a first section, a second section and a connection area. The first section comprises a first rigid frame, an elastic film comprising at least one fluid inlet port; and a first sealing means. The second section comprises a second rigid frame, a fetal bed comprising at least one fluid outlet port and a second sealing means. The connection area comprises at least one opening.
The first and second sections have an open position and a closed position. In the open position a premature mammalian fetus can be placed within the fetal chamber. In the closed position a plurality of latches is configured to create a fluid-tight seal between the first sealing means and the second sealing means to retain the fetal chamber in a closed, fluid tight configuration.
The amniotic fluid circuit is configured to provide an amniotic fluid to and from the fetal chamber. The amniotic fluid circuit comprises: an amniotic fluid unit configured to sterilise the amniotic fluid, and a pump configured to pump the amniotic fluid from the at least one fluid outlet port into the amniotic fluid unit and out from the amniotic fluid unit into the at least one fluid inlet port.
In a particular embodiment of the invention, the fetal chamber further comprises means for preventing the formation of pressure ulcers in the premature mammalian fetus wherein the means for preventing the formation of pressure ulcers are located on the external side of the fetal bed.
In a more particular embodiment of the invention, the means for preventing the formation of pressure ulcers comprises a mattress.
In another particular embodiment of the invention, the fetal bed comprises an umbilical cord protection means.
In another particular embodiment of the invention, the fetal chamber further comprises a bed frame between the fetal bed and the second rigid frame, wherein the bed frame comprises at least two handles configured to facilitate the manipulation of the fetal bed.
In another particular embodiment of the invention, the fetal chamber further comprises one or more additional latches configured to further retain the fetal chamber in a closed, fluid tight configuration at the connection area when a connection means is placed through the at least one opening.
In another particular embodiment of the invention, the fetal chamber further comprises flexible adapter means configured to further retain the fetal chamber in a closed, fluid tight configuration at the connection area when a connection means is placed through the at least one opening.
In another particular embodiment of the invention, the fetal chamber further comprises at least one transversal rigid element at the connection area configured to further retain the fetal chamber in a closed, fluid tight configuration at the connection area when a connection means is placed through the at least one opening.
In another particular embodiment of the invention, the first rigid frame further comprise an opening and the second rigid frame further comprises an opening in the connection area, and wherein the fetal chamber further comprises a light source means configured to illuminate the connection area through said openings.
In another particular embodiment of the invention, the amniotic fluid unit comprises at least one filter, wherein the filter is a physical filter.
In another particular embodiment of the invention, the amniotic fluid unit comprises an antibacterial filter and/or an antiviral filter.
In another particular embodiment of the invention, the amniotic fluid unit comprises an UV (ultraviolet light) treatment unit.
In another particular embodiment of the invention, the amniotic fluid unit is further configured to heat the amniotic fluid and the amniotic fluid unit further comprises a heating unit.
In another particular embodiment of the invention, the amniotic fluid circuit further comprises at least one sensor configured to monitor the amniotic fluid, the at least one sensor selected from the following list: a contamination sensor, a flow, air and/or bubble sensor, and/or a temperature sensor.
In another particular embodiment of the invention, the fetal chamber further comprises at least one outlet debris port.

Brief description of the drawings

To enable a better understanding of the present disclosure, and to show how the present disclosure may be carried out, reference will now be made, by way of example only, to the accompanying schematic drawings, wherein:

Figure 1 shows a schematic view of a system for maturing a premature mammalian fetus according to one or more embodiments of the present invention.
Figure 2 shows an exploded view of a fetal chamber according to one or more embodiments of the present invention.
Figure 3 shows an upper isometric view of another fetal chamber according to one or more embodiments of the present invention.
Figure 4 shows a lower isometric view of the fetal chamber of Fig. 3 according to one or more embodiments of the present invention.
Figure 5 shows an isometric view of another fetal chamber in an open position according to one or more embodiments of the present invention.
Figure 6 shows a top view of another fetal chamber according to one or more embodiments of the present invention.
Figure 7 shows a front view of another fetal chamber according to one or more embodiments of the present invention.
Figure 8 shows a lateral view of another fetal chamber in a closed position according to one or more embodiments of the present invention.
Figure 9 shows a lateral view of another fetal chamber in an open position according to one or more embodiments of the present invention.
Figure 10 shows a frontal cross section of another fetal chamber according to one or more embodiments of the present invention.
Figure 11 shows a lateral cross section of the fetal chamber of Fig. 10 according to one or more embodiments of the present invention.
Figure 12 shows a lateral cross section of a connection area of another fetal chamber according to one or more embodiments of the present invention.
Figure 13 shows a longitudinal cross section of a canulation area of another fetal chamber according to one or more embodiments of the present invention.
Figure 14 shows a cross section of the latching mechanism of another fetal chamber according to one or more embodiments of the present invention.
Figure 15 shows a cross section of the first and second sections opening mechanism of another fetal chamber according to one or more embodiments of the present invention.
Figure 16 shows an isometric view of a fetal bed according to one or more embodiments of the present invention.
Figure 17 shows a top view of a fetal bed according to one or more embodiments of the present invention.
Figure 18 shows a front view of another fetal bed according to one or more embodiments of the present invention.
Figure 19 shows a lateral view of another fetal bed according to one or more embodiments of the present invention.
Figure 20 shows a lower isometric view of another fetal bed and a flexible adapter means according to one or more embodiments of the present invention.

Description of the invention

Definitions

It must be noted that, as used herein, the singular forms "a", "an", and "the", include plural references unless the context clearly indicates otherwise. Further, unless otherwise indicated, the term "at least" preceding a series of elements is to be understood to refer to every element in the series. Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the present invention.
It is noted that the term "about", as used herein, refers to +/- 30%, preferably +/- 20%, preferably +/- 15%, more preferably +/- 10%, of the indicated referred value.
As used herein, the conjunctive term "and/or" between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by "and/or", a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term "and/or" as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term "and/or."
Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step. When used herein the term "comprising" can be substituted with the term "containing" or "including" or sometimes when used herein with the term "having". Any of the aforementioned terms (comprising, containing, including, having), whenever used herein in the context of an aspect or embodiment of the present invention may be substituted with the term "consisting of", though less preferred.
When used herein "consisting of' excludes any element, step, or ingredient not specified in the claim element. When used herein, "consisting essentially of does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.
The term "fetus" refers to a developing mammalian organism, after the embryonic stage and before birth. In humans, this stage begins around the eighth week after fertilization and continues typically until birth between 37 and 42 weeks. During this period, the major structures and organs of the body develop and mature, but it may be different for other species. The term "mammalian fetus" may be used alternatively. Nonetheless, in the context of the present invention, the term fetus will be also used for neonates. Therefore, in the context of the present invention, the term "fetus" also refers to "newborn", preferably to a premature newborn.
The term "premature fetus" refers to a developing mammal that is born before reaching full term gestation. In humans this is typically defined before 37 weeks of gestation, although this may change depending on the species as the skilled person may know.
The term "extremely premature fetus" in a developing mammal refers to the first period of a premature fetus range. In human pregnancy, it is commonly understood that extreme prematurity refers to less than 28 weeks of gestation. In other mammal species, equivalences with human gestation are established according to similar degrees of key organs maturation, i.e. brain, lung, or other organs. The term extreme prematurity may refer to the fetus when is intrauterine, or newborn (or neonate) when this fetus is born. In the context of the present invention, it is understood that an extremely premature newborn has a high rate of mortality and morbidity despite state-of-the-art intensive neonatal care, due to the extreme immaturity of key organs such as lungs, brain, digestive system and others.
The term "to born" refers to the process of a mammalian fetus exiting it's mother womb. This comprises both natural processes as well as artificial or aided processes, such as C-section procedures, for any reason it may be.
The term "maturation" refers to the process through which the fetus undergoes development of its physiological and anatomical structures and functions to reach a state of readiness for survival outside the womb.
The term "fetal chamber" refers to a specialized, controlled physical environment designed to support and sustain the development of a fetus outside the natural womb.
The term "sealing means" refers to a mechanism or piece configured to create a fluid-tight seal between two pieces. A sealing means may be configured to only create a fluid-tight seal when used in combination with another sealing means.
The term "fetal bed" refers to a means configured to support a fetus during its maturation within the fetal chamber. It is preferably configured to mimic the natural conditions of the womb, providing a stable and secure environment for the fetus.
The term "amniotic fluid" in the context of the present invention refers to any fluid either natural or synthetic specially formulated to replicate the properties and functions of the natural amniotic fluid.
The term "pressure ulcer" also known as a "pressure sore", "decubitus ulcer", or "bed sore" refers to a localized injury to the skin and underlying tissue, usually over a bony prominence, resulting from prolonged pressure or friction.
The term "connection area" refers to a specific region of the fetal chamber body where a connection means such as a cannula can be inserted into a blood vessel or other anatomical structure for medical purposes, preferably into the umbilical cord. It is not limited to being configured to comprise a connection means therein nor the cannulation process to be performed therein.

Description

Each embodiment disclosed herein is contemplated as being applicable to each of the other disclosed embodiments. Thus, all combinations of the various elements described herein are within the scope of the invention.
A first aspect of the invention relates to a system for maturing a premature mammalian fetus. As described in the background art, very premature fetus cannot survive without an adequate environment that enables the development of certain capabilities such as breathing, which at these early stages is not yet developed. This first aspect of the invention therefore directs to a system for said maturation of a premature mammalian fetus, with special impact on extremely premature foetus, where mortality and morbidity is usually very high.
As shown in Fig. 2, the system comprises a fetal chamber 100. The fetal chamber 100 is an enclosure designed to house and support the growth and development of a premature mammalian fetus outside the womb. It mimics the natural environment of the uterus.
Preferably, the present invention relates to a fetal chamber 100 which can be in the form of a biomimetic bag a hybrid system, and/or a fluid-filled chamber. Biobags may be understood as a flexible and transparent or translucent enclosures that enables the visualization of the fetus and the surrounding amniotic fluid. Hybrid system, may further comprise rigid components that further support the flexible components. Moreover, the fetal chamber 100 may be fully fluid-filled such that it replicates the amniotic sac.
It is noted that the fetal chamber can have different shapes and sizes depending on the species of animal being supported. For instance, a fetal chamber designed for human use will differ significantly in size and configuration from one intended for smaller animals such as mice or larger animals like sheep. These variations ensure that the chamber provides an appropriate fit and environment, tailored to the specific anatomical and physiological needs of the fetus of each species. Therefore, the skilled person may envisage many other shapes and sizes different to those shown in Fig. 2 according to the animal fetus enclosed therein.
The fetal chamber 100 comprises two sections: a first section 110 and a second section 120. This design allows the fetal chamber 100 to be opened and closed when in use, facilitating the introduction of the fetus in a simple and fast manner. The design of the fetal chamber 100 with two sections enhances the practicality and usability of the system, making it easier to manage the delicate process of supporting fetal growth and development outside the womb.
The first section 110 of the fetal chamber 100 is configured to be the upper section, part or lid of the chamber when in use, as shown for example in Fig. 5. The first section 110 comprises a first rigid frame 5, an elastic film 1 and a first sealing means 3.
The first rigid frame 5 provides structural rigidity to the first section 110 of the fetal chamber 100. Thus, the first rigid frame 5 provides the necessary support and protection for the fetus housed within. While first rigid frame 5 typically takes the form of an outer perimeter or shell, encircling the perimeter of the first section 110, the skilled person may envisage many other forms the first rigid frame may take all of which are comprised within the present invention.
The first rigid frame 5 may be construed of different materials as long as they can structurally maintain its shape during its use within the fetal chamber 100. For example, the first rigid frame 5 may comprise aluminium such as 6061 T6 aluminium, although the skilled person may envisage many other alternatives to the same, preferably focusing on being as lightweight as possible and structurally resistant.
The elastic film 1, is configured to provide protection to the fetus from above when in use. This film serves as a crucial barrier, providing a pregnant uterus-like environment that shields the fetus from external elements. Moreover, it allows enough freedom of movement to the fetus, which prevents the formation of ulcers while providing feedback of its environment while ensuring the fetus is kept in a controlled position.
The elastic film 1 is preferably made of a thin material, as it does not need to provide structural support. This allows for flexibility and ease of use while ensuring the necessary protection for the fetus. Depending on the specific requirements, the film may be transparent, translucent, or opaque. Preferably, the elastic film 1 is transparent or translucent to allow for visual monitoring of the fetus. The fetus may be monitored in different ways, for example to detect normal movements such as sucking, respiratory movements as well as abnormal situations such as physical injuries, and/or to detect umbilical cord bleedings and/or sediments such as meconium urine or others.
It is noted that the shape and material of the elastic film 1 can vary depending on the animal and the intended use. It is designed to provide a protective barrier between the fetus and the outer world, ensuring a controlled and safe environment. Additionally, the film preferably possesses insulation properties to maintain an optimal temperature and prevent any adverse effects from external temperature variations.
The elastic film 1 is preferably thin enough, but flexible and resistant, such that it allows for manual inspection of the fetus through said elastic film 1, e.g. manipulation of the fetus, as wells as the inspection using imaging means such as an echography. Therefore, the premature mammalian fetus can easily be accessed through the elastic film 1 for evaluation, repositioning or intervention.
It must be noted the elastic film 1 must be elastic, since this way it provides for enough room for the fetus to move freely within a certain range and further receive feedback of the limits of its environment without harm, as it would do within the womb. As shown in Fig. 3, when the first rigid frame 5 has an annular shape, the elastic film preferably covers the full space the whole space within the first rigid frame 5. In this configuration, the premature mammalian fetus can easily be accessed through the elastic film 1 for evaluation, repositioning or intervention.
The elastic film 1 may be fixed to the first rigid frame 5 or may be an independent piece that is secured to the first rigid frame as will be explained later on.
The elastic film 1 comprises at least one fluid inlet port 2a, 2b, which allows for the provision of fluid into the fetal chamber. The at least one fluid inlet port 2a, 2b, allows the provision of an amniotic fluid or equivalents thereof into the fetal chamber 100, for maintaining the appropriate environment for the fetus. As defined above, the term "amniotic fluid" in the context of the present invention preferably refers to any fluid either natural or synthetic specially formulated to replicate the properties and functions of the natural amniotic fluid. From herein after, the term amniotic fluid will be used to refer to any fluid of this kind.
The at least one fluid inlet port 2a, 2b can be positioned in various locations along the elastic film 1 to suit different needs and configurations. Furthermore, the elastic film 1 can comprise more than one fluid inlet port 2a, 2b, enhancing its versatility and functionality.
For instance, as shown in Fig. 3, the elastic film 1 may include two fluid inlet ports 2a, 2b. Although one of these ports can be utilised for other purposes as will be explained late on, the presence of multiple ports provides flexibility in fluid management. As seen in Figs. 2 and 3, the at least one fluid inlet port 2a, 2b may consist of more than one piece, such as a washer 2a and a tube 2b. The tube 2b is secured on the face of the elastic film 1 that is configured to face the interior of the fetal chamber using the washer 2a. A person skilled in the art may foresee various alternatives to this solution, all of which are encompassed within the scope of the present embodiment.
The first sealing means 3 may come in various forms and shapes to suit different configurations and requirements of the fetus, the fetal chamber and/or the amniotic fluid. This flexibility allows the sealing means to be adapted to specific needs, ensuring an effective seal regardless of the design variations of the fetal chamber. The first sealing means 3 can take various forms and shapes, such as gaskets, O-rings, or other sealing mechanisms commonly used in fluid-tight applications. These sealing components are essential for maintaining the integrity of the chamber, preventing any leakage of fluids, and ensuring a sterile environment for the fetus.
Additionally, when the elastic film 1 is an element independent from the first rigid frame 5, it may be fixed to the first rigid frame 5 through the first sealing means 3, as will be explained below.
The second section 120 of the fetal chamber 100 is configured to be the lower section, part or lid of the chamber when in use, as shown for example in Fig. 5. The second section 120 comprises a second rigid frame 10, an fetal bed and a second sealing means 73.
The second rigid frame 10 provides structural rigidity to the second section 120 of the fetal chamber 100. Thus, the second rigid frame 10 provides the necessary support and protection for the fetus housed within. While second rigid frame 10 typically takes the form of an outer perimeter or shell, encircling the perimeter of the first section 110, the skilled person may envisage many other forms the first rigid frame may take all of which are comprised within the present invention.
As the first rigid frame 5, the second rigid frame 10 may be construed of different materials as long as they can structurally maintain its shape during its use within the fetal chamber 100. For example, the second rigid frame 10 may comprise aluminium, although the skilled person may envisage many other alternatives to the same.
The fetal bed 7 serves as a supportive surface for the fetus within the chamber. The fetal bed 7 is specifically designed to protect the fetus from below and provide a comfortable and stable platform for its development. It is preferably made of a soft and cushioned material to ensure that the fetus is adequately supported and cushioned during its time in the chamber. This material helps to distribute the weight of the fetus evenly and minimizes any potential discomfort or pressure points.
Ideally, the fetal bed 7 is made of a transparent or translucent material, allowing for easy observation of the fetus and its surrounding such as bleedings and sediments such as meconium, urine or others without the need to disturb its environment. However, depending on the specific requirements of the application, it may also be opaque.
The design and material of the fetal bed 7 can vary depending on factors such as the size of the fetus, its weight, and any specific needs or sensitivities it may have. The skilled person may envisage many different shapes other than those disclosed in Figs. 2, 3, 4 and 5 according to the fetus it is designed for. Additionally, the fetal bed 7 is preferably configured to provide insulation properties, helping to maintain a stable temperature within the chamber and protect the fetus from external temperature fluctuations. The fetal bed 7 may be fixed to the second rigid frame 10 or may be an independent element, as it will be explained later.
The fetal bed 7 further comprises at least one fluid outlet port 71. The at least one fluid outlet port 71 enables the extraction of fluids from the fetal chamber. It is noted that the at least one fluid outlet port 71 may be located in different positions along the fetal bed 7 to accommodate the fluid management needs and ensure optimal operation of the fetal chamber 100.
The fetal bed 7 may incorporate more than one fluid outlet port 71. For instance, as shown in Figs. 2 and 4, the fetal bed may comprise more than one fluid outlet ports 71. While one port is primarily used for fluid extraction, the other may be purposed for different functionalities, as will be detailed further below.
As shown in Figs. 16, 17, 19, and 20, the fluid outlet port 71 may include a plug 715 designed to provide a fluid-tight seal when the port is not in use. This ensures that the internal environment of the fetal chamber remains uncontaminated and stable.
Besides the plug 175, other embodiments may feature a valve or a self-sealing mechanism for one or more of the at least one fluid outlet port 71. These alternatives are designed to allow fluid to flow out of the fetal chamber only under specific conditions, for example only when determined connector is connected to the fluid outlet port 71.
The second sealing means 73, is configured to ensure a fluid-tight seal between the first section 110 and the second section 120 of the fetal chamber 100, as will be explained below. As with regard to the first sealing means 3, the second sealing means 73 can come in different forms and shapes, tailored to fit the specific design and requirements of the fetal chamber 100. The first sealing means 3 can take various forms and shapes, such as gaskets, O-rings, or other sealing mechanisms commonly used in fluid-tight applications.
The second sealing means 73 may be comprised within the fetal bed, as illustrated in Fig. 2. However, in other embodiment of the present invention the second sealing means 73 can be an independent element for the second section 120 of the fetal chamber 100.
The fetal chamber 100, further comprises a connection area 17, as can be seen for example in Figs. 2, 6, 12, 13, 17 and 20. While these figures depict a particular connection area 17, it is noted that the connection area 17 may take different shapes depending on the needs of the fetus. It may be wider, thinner, shorter or longer, and may comprise more or less elements as those shown in Figs. 2, 6, 12, 13, 17 and 20. As shown with respect to Figs. 2, 6, 12, 13, 17 and 20, the connection area 17 may be comprised by both the first section 110 and the second section 120 of the fetal chamber 100. However, the connection area 17 may be comprised only in one of the first 110 or second 120 sections of the fetal chamber 1000.
The connection area 17 is configured to provide a safe area where the fetus' umbilical cord can be connected to a cannula system to meet the essential requirements for its respiration, nutrition, hormonal, and excretion systems. The at least one opening 171, which allows the provision of at least one connection means such as a cannula, a tube, or an umbilical cord section through the fetal chamber 100 to connect the umbilical cord of the premature mammalian fetus to a life-supporting machine. In a particular preferred embodiment, the connection area 17 comprises at least two openings 171, one configured for an umbilical arteria connection and other one configured for an umbilical vein connection. According to the present invention, the cannulation process may be performed in said connection area 17 or outside the connection area 17, for example in the womb of the mother. The skilled person may envisage many different ways in which this connection means may be materialised.
The life-supporting machine may include at least one ECMO (Extracorporeal Membrane Oxygenation) system and may comprise additional systems configured to enable the appropriate support and growth for the fetus. As shown, for example, in Figs. 3 to 5, the connection area 17 may include three openings 171. However, it is noted that it may comprise more or fewer openings 171, and when it includes at least two openings, the openings may have different sizes and shapes between them.
As shown in Figs. 2, 12, and 13, the connection area 17 may also include further means 6, 8 configured to adapt to different connection means. These means 6,8 ensure a fluid-tight configuration of the fetal chamber 100, even when said connection means are provided through the fetal chamber 100, as will be explained below.
In this first aspect of the invention, the first section 110 and the second section 120 have an open position as shewn for example in Figs. 5 and 9 where a premature mammalian fetus can be placed within the fetal chamber 100, and a closed position. In the closed position a plurality of latches 12, 15 is configured to create a fluid-tight seal between the first sealing means 3 and second sealing means 73 to retain the fetal chamber 100 in a closed, fluid-tight configuration.
As shown in Fig. 14, the latch 15 is configured to held together the first rigid frame 5 and the second rigid frame 10 together. Between them, the first sealing means 3 and the second sealing means 73 keep together the elastic film 1 and the fetal bed 7 to ensure the fetal chamber is closed in a fluid-tight configuration. The fetal chamber 100 may comprise many other elements which are optional for the present embodiment and which will be explained later on with regard to preferred embodiments. Fig. 15 shows another cross section of a fetal chamber 100 at another section wherein the first section 110 and the second section 120 are joined through a hinge 11, although this is optional for the present embodiment and will be explained later on with regard to preferred embodiments. Still, it can be noticed how the first sealing means 3 and the second sealing means 73 keep together the elastic film 1 and the fetal bed 7 to ensure the fetal chamber is closed in a fluid-tight configuration.
Advantageously, a system for maturing a premature mammalian fetus comprising a fetal chamber 100 as described herein, provides an easy-to-access design, while ensuring the premature fetus is preserved in the most biomimetic conditions in terms of proprioceptive feedback for the fetus and that minimises the risk of infection of the fetal chamber. This fetal chamber 100 is particularly useful for early premature fetuses, such as extremely premature fetuses, where the mortality and morbidity rates are over 90%. However, it is noted any type of premature fetus can benefit from this fetal chamber 100.
It is noted that Fig. 1 shows a schematic view of a system for maturing a premature mammalian fetus according to one or more embodiments of the present invention. However, it must be noted that it discloses many other elements such as bags 19, 21, filters 23, 24, 25, 26, 27, ports 29, probes, and sensors, 31, 32, 33 and 34 that may not be comprised in the system according to the present embodiment. Moreover, the fetal chamber and amniotic fluid unit may take different shapes, forms and sizes to that of Fig. 1, as the skilled person may note. All of this are fully comprised in the present invention.
It is also noted that Figs, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15 show different views of multiple fetal chambers according to one or more embodiments of the present invention. They also comprise multiple other ports, frames, seals beds and windows that may not be comprised in the system according to the present embodiment and that will be explained later on with respect to preferred embodiments. Likewise, the fetal chamber 100 and all its components may take different shapes and sizes or may be located in other places as the skilled person may envisage, all of which are deemed to be fully comprised in the present invention.
Figs. 16, 17, 18, 19 and 20 show different views of multiple fetal beds 7 according to one or more embodiments of the present invention. They also comprise multiple other ports, seals, protectors, and openings that may not be comprised in the system according to the present embodiment. Likewise, the fetal chamber and all its components may take different shapes and sizes or may be located in other places as the skilled person may envisage, all of which are deemed to be fully comprised in the present invention.
In a preferred embodiment of the first aspect of the invention, As shown in Fig. 1 the system further comprises an amniotic fluid circuit configured to provide an amniotic fluid to and from the fetal chamber 100. The amniotic circuit comprises an amniotic fluid unit 200 and a pump 22.
The amniotic fluid unit 200 is configured to sterilise the amniotic fluid. The primary function of the amniotic fluid unit 200 is to sterilise the fluid to guarantee its asepsis. This is crucial for maintaining a sterile environment within the fetal chamber, preventing infections and promoting healthy development of the fetus.
The amniotic fluid unit 200 may incorporate various methods to achieve sterilisation. These methods can be combined to ensure comprehensive asepsis. For example, it may comprise filters with different sizes designed to remove particulate matter and microorganisms from the amniotic fluid, bacterial and viral filters configured to target bacterial and viral contaminants and/or ultraviolet (UV)filtration units, to neutralise pathogens; all of which will be explained later with respect to further preferred embodiments.
The pump 22 is configured to pump the fluid from the at least one fluid outlet port 71 into the amniotic fluid unit 200 and out from the amniotic fluid unit 200 into the at least one fluid inlet port 2a, 2b.
The pump 22 may be configured in different ways. For example, the pump 22 may be configured to pump continuously or it may be configured to pump intermittently. It may be also configured to pump when a specialised sensor determines it is desired to pump, for example because a risk of infection is determined or certain time threshold has been reached.
The pump 22 can be of various types, as the person skilled in the art would envisage. For example it may be a peristaltic pump, a diaphragm pump, a centrifugal pump, or a gear pump among others. Each type of pump offers different advantages depending on the specific requirements of the system.
It is noted that in some embodiments of the present preferred embodiment, the pump 22 may be integrated into the amniotic fluid unit.
It is also noted that the fetal chamber 100, the amniotic fluid unit 200 and the pump 22 may be connected by one or more tubular connections 28 as shown in Fig. 1 and as the skilled person may easily envisage using the general common knowledge.
Advantageously, a system comprising a fetal chamber 100 and an amniotic fluid circuit as above-defined, forms an pregnant uterine-like environment for the maintenance of homeostasis in the premature fetus outside of the womb which can prevent and treat the development of bacteria and viruses in a more environmentally friendly and biomimetic way. This system is particularly useful for early premature fetuses, such as extremely premature fetuses, where the mortality and morbidity rates are over 90%. However, it is noted any type of premature fetus can benefit from this fetal chamber 100. Since the amniotic fluid is cycled through the amniotic fluid unit 200, there is no need for continuously replacing the amniotic fluid, which is more cost effective and better for the environment as the use of amniotic fluid is more efficient. Moreover, since the amniotic fluid unit 200 is configured to sterilise the amniotic fluid but not to completely discard all non-aqueous elements, such as hormones, proteins, nutrients and other biochemical products, the amniotic fluid within the proposed system can replicate the natural amniotic fluid conditions. Since the amniotic fluid is known to have a relevant impact on the development of the fetus, this can have a further biological impact on the survival rates of the fetus during and after the delivery.
The term "delivery" in the context of the present invention refers to the stage wherein the premature mammalian fetus is ready to be removed from the fetal chamber as it is developed enough to no longer require such fetal chamber. Therefore, even if the fetus may have been prematurely delivered by the mother, it it's still understood that it's yet to be delivered in a viable condition.
In another preferred embodiment of the first aspect of the invention, the fetal chamber 100 further comprises means 75 for preventing the formation of pressure ulcers in the premature mammalian fetus. Pressure ulcers, also known as bedsores, are injuries to the skin and underlying tissue resulting from prolonged pressure on the skin. They commonly occur in areas where the skin covers bony prominences, such as the back, hips, and heels. In the context of a fetal chamber, these ulcers can develop at any point of sustained contact between the fetus and the support surface, such as the fetal bed 7.
To address the risk of pressure ulcers in the fetal chamber 100, several types of means 75 can be employed. These means are designed to distribute pressure evenly and reduce the risk of localized pressure build up, which can compromise skin integrity and lead to ulceration. For example, an air mattress, a water filled mattress, a massaging mattress or a fetal positioning device constitute means 75 for preventing the formation of pressure ulcers in the premature mammalian fetus. They all have in common that the fetus position is modified continuously to avoid the fetus to be supported continuously by the same surface are of their body.
The means 75 for preventing pressure ulcers can be adapted to the specific characteristics of the fetus, such as size, weight, and shape. For example, heavier fetuses may require more robust support systems, while smaller fetuses might benefit from softer, more flexible materials. Also depending on the shape and size of the premature mammalian fetus, the means 75 for preventing the formation of pressure ulcers in the premature mammalian fetus may change in shape or size.
The fetus located on the fetal bed 7 not only may suffer from pressure ulcers, which may be further minimised with a better cushion on the fetal bed 7, but it can generate fluid blind spots around itself wherein the amniotic fluid can easily become stagnant. If the fluid becomes stagnant, the amniotic fluid circuit cannot process said amniotic fluid, which in turn means the asepsis of the amniotic fluid is at risk. By providing means 75 for preventing the formation of pressure ulcers in the premature mammalian fetus, the fluid blind spots are reduced or removed, and the fluid does not stay stagnant, ensuring that the amniotic fluid enters into the amniotic fluid circuit to be sterilised by the amniotic fluid unit 200. Furthermore, as the amniotic fluid keeps circulating, the amniotic fluid does not lose its temperature, so cold points around the fetus are also avoided.
Advantageously, it has been noted that the provision of means 75 for preventing the formation of pressure ulcers in the premature mammalian fetus not only prevent the surge of pressure ulcers, but it further ensures that the fluid does not get stagnant in places around the fetus body, particularly, under the fetus.
In a more preferred embodiment, as shown for example in Figs. 14 and 15 the means 75 for preventing the formation of pressure ulcers are located on the external side of the fetal bed 7. Since the fetal bed 7 is the one supporting the fetus, this means that in use the means 75 are located under the fetus.
It is noted that the means 75 may take different shapes, sizes of that of Figs. 14 and 15 they may comprise thinner and thicker sections depending on the fetus the fetal chamber 100 may be designed for.
Advantageously, the amniotic fluid located in the fluid blind spots is directly stimulated, which in turn favours ensures that the amniotic fluid does not get stagnant in places around the fetus body, particularly, under the fetus.
In a further preferred embodiment, the means 75 for preventing the formation of pressure ulcers comprises a mattress.
It is noted that there are several types of mattresses designed for this purpose, such as air mattresses, water mattresses or motor mattresses. Mattresses configured for preventing the formation of pressure ulcers work by alternating the pressure the mattress applies onto the fetal bed 7. This alternating pressure helps to change the contact points between the fetus and the mattress 75, reducing the risk of prolonged pressure on any single area and mobilising the amniotic fluid. These mattresses can be programmed to adjust the frequency and intensity of the pressure changes. Air fluidized mattresses contain air-permeable beads that create a fluid-like support surface when air is forced through them. This fluidized surface conforms to the body shape of the fetus, distributing weight and pressure evenly, and therefore impeding the generation of fluid blind spots for the amniotic fluid.
Advantageously, mattresses are a cost-effective and easily configurable means 75 for preventing the formation of pressure ulcers, which ensures that the fluid does not get stagnant in places around the fetus body, particularly, under the fetus.
In another preferred embodiment of the first aspect of the invention, as shown for example in Figs. 2 and 5, the fetal chamber 100 further comprises a bed frame 9 between the fetal bed 7 and the second rigid frame 10.
Since the fetal bed 7 is configured to be supported by the second rigid frame 10 when in use, the provision of a bed frame 9 between both means that the bed frame can actually provide a frame to the fetal bed 7, so that the bed frame 9 can be used to give structural support the fetal bed 7 when being transported.
It is noted that the bed frame 9 shown in Figs. 2 and 5 has a particular shape and size and other elements comprised therein, but the skilled person may further envisage many other alternatives for a bed frame 9 according for example to the fetal bed 7 shape, size, weight, and to the type of mammalian the fetal bed its configured to hold. All of these alternatives are also comprised within the present disclosure.
Advantageously, this facilitates the manipulation of the fetal bed from and onto the second rigid frame 10. This is particularly important during the placement of the premature mammalian fetus within the fetal chamber 100, as cannulation is typically performed within the womb or close to it and the cannulated fetus is later transported into the fetal chamber 100.
By providing a bed frame 9, when in use the premature mammalian fetus can be placed into the fetal bed 7 as close to the womb as possible during the transfer from the mother womb to the fetal chamber 100, and the fetal bed 7 can be then easily moved to the fetal chamber 100, to be placed over the second rigid frame 10.
In this particular embodiment, the bed frame 9 preferably comprises at least two handles 91 configured to facilitate the manipulation of the fetal bed 7, as shown in Figs. 2 and 5. The provision of at least two handles 91 further facilitates the transport of the fetal bed 7 to the second rigid frame 10 to introduce the premature mammalian fetus into the fetal chamber 100, reducing the time until the fetus is fully enclosed within the fetal chamber 100 and therefore reducing the risks of contamination and temperature loss.
It is noted that the handles 91 may take different shapes and configurations to the handles of Figs. 2 and 5. For example, the bed frame 9 may comprise fixed handles or foldable handles, they may be adjustable and have different ergonomic shapes. Also, the bed frame 9 may comprise more than two handles, for example to facilitate the transport of the fetal bed 7 into the second rigid frame by more than one person.
In another preferred embodiment of the first aspect of the invention, and as shown in Figs. 2,3,4,5 and 6, 12 and 13 the fetal chamber 100 further comprises one or more additional latches 12 configured to further retain the fetal chamber 100 in a closed, fluid-tight configuration at the connection area 17 when a connection means is placed through the at least one opening 171. The one or more additional latches 12 may be as the latches 15 as described above, or may be specifically designed to produce more or less force onto the connection area 17, as the skilled person may envisage.
A connection means may be any means such as a cannula, catheter or a tube, configured to be inserted into the fetal chamber to connect the umbilical cord of the premature mammalian fetus with any life supporting device, preferably a blood oxygenator such as an ECMO.
The connection area 17 is a specially sensitive area of the fetal chamber 100, since it comprises at least one opening 171 for a connection means to cross it. This means there is an additional element, usually in a tubular shape which increase the surface of the seal between the first section 110 and the second section 120, and it further makes it less predictable as these connection means can change between fetuses or applications.
As shown for example in Figs. 12 and 13, the provision of the one or more additional latches 12 brings the first rigid frame 5 and the second rigid frame 10 together. Then the first sealing means 3 and the second sealing means 73 can fluid-tight seal these parts to define a closed fetal chamber 100. Other means configured to further increase the seal between the first rigid frame 5 and the second rigid frame 10 may be used additionally or alternatively, as will be explained now.
In another preferred embodiment of the first aspect of the invention, and as shown in Figs. 2, 3, 4, 5, 6, 7, 12, 13, 16, 17 and 20 the fetal chamber 100 further comprises flexible adapter means 6 configured to further retain the fetal chamber 100 in a closed, fluid-tight configuration at the connection area 17 when a connection means is placed through the at least one opening 171.
The flexible adapter means 6 have two functions: it serves as an adapter to the specific connection means the fetal chamber 10 may require for the fetus, and it further increases the fluid-tight, seal of the connection area 17 along the opening 171 length, as can be seen in Fig. 12.
Since due to the at least one opening 171 the connection area 17 is a critical sealing area to generate a fluid-tight fetal chamber 100, the provision of flexible adapter means 6 that are flexible to adapt to any force applied therein such as the force applied by the one or more additional latches 12 and that they are further an adapter such that they are specifically configured to adapt to the shape of the connection means used thereof is very beneficial to further ensure the fluid tightness of the fetal chamber even when connection means are introduced through the at least one opening 171. For example, if one of the at least one opening 171 is not used, the flexible adapter means 6 can further comprise means to block one or more of aid openings 171 while not in use.
It is noted that Figs. 12, 13 and 20 show a particular flexible adapter means 6 configured to adapt to a particular type of connection means and adapted for the particular connection area 17 of the fetal chamber 100 displayed, but the skilled person may envisage many other different alternatives to the same, such as different sizes, shapes and adaptations such as for more or less openings 171, all of which are comprised within the present invention.
As shown in Figs. 2, 5, 12 and 13, in a more preferred embodiment, the fetal chamber 100 further comprises at least one transversal rigid element 8 at the connection area 17 configured to further retain the fetal chamber 100 in a closed, fluid-tight configuration at the connection area 17 when a connection means is placed through the at least one opening 171.
The rigid element 8 shall be essentially transversal to one or more of the at least one opening 171, such that it works as a further pressure point to prevent any fluid from escaping from the fetal chamber 100 through connection area 17.
In combination with the flexible adapter means 6 it benefits from the flexibility of the flexible adapter means 6 to further increase the seaming pressure at the connection area 17.
In another preferred embodiment of the first aspect of the invention, and as shown in Figs, 2 and 6 the first rigid frame 5 further comprise an opening 51 and the second rigid frame 10 further comprises an opening 104 in the connection area 17. Moreover, the fetal chamber 100 further comprises a light source means 18 configured to illuminate the connection area 17 through said openings 51, 104.
It is noted that the openings 51 and 104 of the first rigid frame 5 and the second rigid frame 104, respectively, may be empty openings or may be filled with any transparent or translucent material, therefore enabling the light from the light source means 18 to be able to illuminate the connection area 17 through said openings 51, 104
The openings 51, 104 may take the same shape or be different between them, and may be different to those shown in Figs. 2, 5, as long as they allow a light beam to cross through them.
The light source means 18 are preferably located on the external side of the second rigid frame 10, such that in use they illuminate from below the connection area 17 and the light can be seen through the openings 51, 104 from above. It is noted that the light source means 18 may be of different types such as LED lights, fluorescent lights, incandescent bulbs or halogen lamps among others, as the skilled person may envisage.
Advantageously, a background light crossing the connection area 17 allows for the evaluation of the seal tightness and determine any possible problems associated with the connection means through the opening 171. In particular, air, blood, blood clots and fluid leaks can be spotted and the cannulation can be adjusted if necessary.
If blood leaks out from the connection means into the amniotic fluid it becomes a source of waste and a potential biological risk, leading to a viability risk for the fetus. Therefore, the provision of these openings 51, 104 and the light source means 18 further contributes to the provision of an extracorporeal system for the maintenance of homeostasis in the premature fetus outside of the womb that can prevent and treat the development of bacteria and viruses in a more environmentally friendly and biomimetic way.
In another preferred embodiment of the first aspect of the invention, and as shown in Fig. 1 the amniotic fluid unit 200 comprises at least one filter, wherein the filter is a physical filter 23, 24. Physical filters are aimed at removing the sediments in suspension on the amniotic fluid. The physical filters may be of many types as the skilled person may envisaged, such as surface filters or depth filters of any kind. Advantageously, a physical filter enables the removal of the physical debris from the amniotic fluid.
In a more preferred embodiment, the amniotic fluid unit 200 comprises at least one physical filter 23, 24, wherein the filter is of at most of 100µm. Advantageously, a filter of at most 100 µm allows for efficiently filtering particles equal or bigger than 100.
In another more preferred embodiment, the amniotic fluid unit 200 comprises at least one physical filter 23, 24, wherein the filter is at most of 5µm. Advantageously, a filter of at most 5 µm allows for efficiently filtering particles equal or bigger than 5 µm.
It is noted that while Fig. 1 depicts both filters, according to the present invention the amniotic fluid unit may comprise only one of the filters, or may comprise more filters.
It is also noted that while any order of filters may be employed, as shown in Fig. 1 it is preferred for bigger size filters 23 to be placed before smaller filters 24 in the sense of the fluid, so that smaller filters are not clogged with bigger particles.
In another preferred embodiment of the first aspect of the invention, as shown for example in Fig. 1, the amniotic fluid unit 200 comprises an antibacterial filter 25. The antibacterial filter 25 is configured to capture and/or inhibit the growth or kill bacteria present in the amniotic fluid passing through it. The antibacterial filter 25 may be of different types according to one or more embodiments, such as a mechanical filter, a chemical filter or a biological filter.
Additionally or alternatively, the amniotic fluid unit 200 comprises an antiviral filter 26. The antiviral filter 26 is configured to prevent the transmission or neutralize the activity of viruses present in the fluid passing through it. The antiviral filter 26 may be of different types according to one or more embodiments, such as a size-exclusion filter, an electrostatic filter, a chemical filter or a biological filter.
Advantageously, the fluid that is processed by the amniotic fluid unit 200 has its bacteria and/or viruses removed, which ensures the sterility of the amniotic fluid. In the context of the present invention a filter may remove and/or may just kill or neutralise the bacteria and/or the viruses.
It is noted that in Fig. 1 both the antibacterial and the antiviral filters 26, 25 are shown but in other embodiments of the present preferred embodiment only one of them may be included into the amniotic fluid unit 200, or may be included in different order.
It is noted that when more than one filter is used, the antibacterial filter 26 and/or antiviral filter 25 are preferably placed after the physical filters 23, 24, so that the antibacterial filter 26 and/or antiviral filter 25 do not get clogged by big particles.
In another preferred embodiment of the first aspect of the invention, the amniotic fluid unit 200 comprises an ultraviolet (UV) treatment unit 27. The UV treatment unit 27 is configured to provide UV lights, which is particularly effective at inactivating microorganisms. When microorganisms such as bacteria, viruses, and fungi are exposed to UV light at the appropriate wavelength, the UV radiation penetrates their cell membranes and damages their DNA. This damage prevents the microorganisms from replicating and renders them unable to cause infection. Advantageously, UV treatment selectively targets microorganisms while leaving the fluid itself largely unaffected. The energy from the UV light is absorbed by the genetic material of the microorganisms, effectively neutralizing them without causing significant changes to the fluid's composition or properties.
In a particularly preferred embodiment of the first aspect of the invention, the amniotic fluid unit 200 comprises a physical filter 24 of at most of 5µm before the UV treatment unit 27. Advantageously, this avoids elements bigger than 5 µm can project a shadow onto bacteria when the UV light is applied, making the UV treatment less efficient.
In another preferred embodiment of the first aspect of the invention, the amniotic fluid unit 200 is further configured to heat the amniotic fluid and the amniotic fluid unit 200 further comprises a heating unit 27. Maintaining the amniotic fluid at an appropriate temperature is crucial for the fetus. As the amniotic fluid circulates through the amniotic fluid circuit 200, it tends to lose heat, potentially dropping to a temperature lower than optimal for the premature mammalian fetus.
Deviations from the optimal temperature range can adversely affect fetal development and viability. Therefore, the heating unit 27 serves to counteract heat loss and ensure that the amniotic fluid remains within the desired temperature range conducive to fetal growth and development.
The heating unit 27 can be controlled by a processing unit, which may rely on sensors or pre-calibrated settings to monitor and adjust the temperature of the fluid as needed. Sensors can detect the temperature of the fluid within the amniotic fluid unit 200 and provide feedback to the processing unit, which then adjusts the output of the heating unit accordingly.
In a preferred embodiment, the heating unit 27 is configured to maintain the amniotic fluid at a preferred temperature range. The skilled person may easily determine the appropriate temperature range for the fetus, which may vary between species. For example, for a human fetus, this temperature range may be comprised between 30 - 42°C, although this may be higher or lower depending on the requirements of the fetus. In a particular preferred embodiment, for a human fetus, the temperature range is comprised between 36 and 38°C.
In another preferred embodiment of the first aspect of the invention, and as shown for example in Fig. 1 the heating unit and the UV treatment unit are the same unit 27. This allows for a more compact design, which is desirable in a fetal chamber, since it is more compact and efficient, as there is less heat loss between the heater and the fetus, the heater requires less temperature to achieve the same temperature on the chamber and it is more energy efficient that other solutions such as heat lamps. In a particular preferred embodiment, the heating unit and the UV treatment unit are the same unit 27, and the unit is configured to heat the amniotic fluid by immersing a tube comprising the amniotic fluid in a hot liquid, preferably water.
It is noted that according to another embodiment, the heating unit 27 may be comprised within the fetal chamber 100, for example associated to the means 75 for preventing the formation of pressure ulcers in the premature mammalian fetus. For example, a mattress 75 may be further equipped with the heating unit 27, such that heat is provided directly to the fetus and the amniotic fluid comprised within the fetal chamber 100.
In another preferred embodiment of the first aspect of the invention, the amniotic fluid circuit further comprises at least one input port configured to allow for the provision of one or more elements into the amniotic fluid. These one or more elements: proteins, hormones, antibiotics, growth factors, and/or aminoacids. Advantageously, this allows the adaptation of the amniotic fluid to the requirements of the premature mammalian fetus, and to make the amniotic fluid more biomimetic.
In another preferred embodiment of the first aspect of the invention, the amniotic fluid circuit further comprises at least one sensor configured to monitor the fluid. Advantageously, the amniotic fluid unit 200 may be activated and/or its functioning modified according to the needs of the amniotic fluid, i.e. if the at least one sensor determines the amniotic fluid unit 200 is required to sterilise or heat the amniotic fluid, then it can be activated as required.
In a more preferred embodiment, the at least one sensor is a contamination sensor 33. The contamination sensor 33 is designed to detect the presence of various contaminants in the amniotic fluid, which could potentially compromise its safety and efficacy. The contamination sensor 33 may be a microbial sensor, a chemical sensor, a particulate sensor, a pH sensor a conductivity sensor or a combination of two or more thereof. The skilled person may envisage many ways in which these contamination sensors may be configured.
The contamination sensor may be located before the amniotic fluid unit 200, and if the amniotic fluid circuit comprises more than one contamination sensor 33, then additional contamination sensors may be located after the amniotic fluid unit 200 to monitor its effectiveness.
The contamination sensor 33 may be used to control the pump 22 to sterilise the amniotic fluid through the amniotic fluid unit 200. For example, if the contamination sensor 33 detects contaminants in the amniotic fluid, it may trigger the pump 22 through a processor to circulate the fluid through the amniotic fluid unit 200.
The sensor may monitor the amniotic fluid continuously, allowing for real-time adjustments in the pump 22 speed to ensure sterilization. Once contamination levels are below a predefined threshold, the pump 22 may be stopped or configured at a minimum pace to reduce energy consumption.
In another more preferred embodiment, the at least one sensor is a flow, air and/or bubble sensor 31. These sensors are designed to ensure the absence of blockages, air or irregularities in the amniotic fluid circuit.
The flow, air, and/or bubble sensor 31 may be used to determine the presence of an air bubble in the fluid by detecting deviations from the expected flow pattern or by directly sensing the air bubble's acoustic or optical properties. When an air bubble is detected, the sensor 31 may send a signal to a processing unit, which can then take corrective action, such as stopping the pump or adjusting flow rates, to expel the air bubble from the fluid circuit. Alternatively, or additionally, the amniotic fluid unit 200 may further comprise a bubble/air removing system (not shown) configured to remove said air bubble, or an alert can be provided to an expert for the bubble to be manually removed.
The flow, air and/or bubble sensor 31 may be positioned after the amniotic fluid unit 200 to ensure the amniotic fluid unit 200 has not introduced any bubble into the fetal chamber 100, or is blocked.
In another more preferred embodiment, the at least one sensor is a temperature sensor 32. The temperature sensor 32 may be a thermocouple, resistance temperature detector (RTD), thermistor, and/or a semiconductor temperature sensor.
By integrating a temperature sensor 32 with the heating unit 27 of the amniotic fluid unit 200, the amniotic fluid unit 200 can be able to maintain the fluid temperature within the optimal range for the fetal development within the fetal chamber 100.
In another preferred embodiment of the first aspect of the invention, and as shown for example in Figs. 16, 17, 18, 19 and 20, the fetal chamber 100 further comprises at least one outlet debris port 71. Advantageously, the provision of at least one outlet debris port 71 enable the removal of debris accumulated without depending on the amniotic fluid unit 200.
The at least one outlet debris port 71 may be located in the lowermost part of the fetal chamber, as shown in Figs. 1, 18 and 19. However, in other embodiments, the at least one outlet debris port 71 may be located in the first section 110 of the fetal chamber, such as in the elastic film 1 or in the first rigid frame 5.
The at least one outlet debris port 71 may be configured to receive a debris suction probe 30 as shown in Fig. 1, which can be directed within the fetal chamber to remove any debris that may be identified.
In a more preferred embodiment and as shown in Fig. 1, the debris suction probe 30 comprises one or more one-way valves which impede the debris from entering through the outlet debris or the amniotic fluid from leaking through port 71.
In another preferred embodiment of the first aspect of the invention, and as shown for example in Figs. 2, 5, and 15 the first section 110 and the second section 120 of the fetal chamber 100 can move between the open and closed position through a hinge 11. In a more preferred embodiment, the hinge 11 comprises a quick-release mechanism.
The quick-release mechanism may be any quick release mechanism such as a threaded rod mechanism wherein the hinge 11 comprises a threaded rod and nut arrangement. By manually unscrewing the nut, the components attached to the rod can be quickly released from each other. Another type of quick-release mechanism may be a rotate-to-free mechanism, which involves a rotating action to disengage or release the first section 110 from the second section 120 of the fetal chamber 100. The skilled person may easily envisage many other alternative quick-release mechanism
Advantageously, if an intervention into the fetus through the elastic film 1 or if the elastic film 1 breaks, the first section 110 can be quickly replaced with a spare first section 110, which reduces the risks of contamination during said procedure.
In another preferred embodiment of the first aspect of the invention as shown in Figs 1 and 2, the elastic film 1 may further comprises an air outlet 2a, 2b, 29. The air outlet serves to remove accumulated air from the upper part of the chamber. It is noted that when the elastic film 1 comprises more than one fluid inlet port 2a, 2b, the air outlet may be one of the fluid inlet ports.
This may be the same as one of the fluid inlet ports, that may be used occasionally to remove air which accumulates in the upper part of the fetal chamber or to extract amniotic fluid samples directly from the fetal chamber. By this way, the operators can selectively open the designated fluid inlet port to release trapped air without requiring separate dedicated outlets, simplifying the operation and maintenance of the fetal chamber 100. It is noted that all the characteristics above-mentioned for the at least one fluid inlet port 2a, 2b, can be further applied to the air outlet. 2a, 2b, 29.
In another preferred embodiment of the first aspect of the invention, as shown in Fig. 2 the first section 110 further comprises a first film frame 4 between the first sealing means 3 and the elastic film 1, configured to further retain the fetal chamber 100 in a closed, fluid-tight configuration.
It has been found that a rigid frame located between the first sealing means 3 and the elastic film 1 further ensures the elastic film is appropriately sealed, preventing its detachment from the first rigid frame 5.
At the same time, when the elastic film is independent from the first rigid frame 5, the film frame 4 allows for an easy removal of the elastic film 1 from the first rigid frame 5 by removing the film frame 4 from the first rigid frame 5.
In a more preferred embodiment of the first aspect of the invention, as shown in Fig. 2 the first section 110 further comprises a second film frame 4', between the first sealing means 3 and the elastic film 1, configured to form a tongue and groove joint in combination with the first film frame 4 to further retain the fetal chamber 100 in a closed, fluid tight configuration. Advantageously, the tongue and groove joint tightly seals the elastic film 1 to prevent amniotic fluid from escaping the fetal chamber 100.
In another preferred embodiment of the first aspect of the invention, the fetal bed 7 comprises one or more of the following materials: an elastomer and/or silicone.
Advantageously, having a fetal bed 7 comprising one or more of an elastomer and/or silicone further provides cushion and feedback to the fetus, biomimeticing the uterus.
In another preferred embodiment of the first aspect of the invention as shown for example in any of Figs. 2 to 5, the second rigid frame 10 further comprises three or more legs 16.
Since the second rigid frame 10 is preferably configured to be used as the lower section of the fetal chamber 100, and therefore to sustain the fetal chamber 100, the provision of at least three legs 16 ensures the second rigid frame 10 can save the space between the surface the fetal chamber 100 is placed on and the lowest part the fetal bed 7 may reach once the fetus is placed inside the fetal chamber 100. It is noted that depending on the fetus or the fetal chamber 100, the at least three legs 16 may be longer, or shorter, or take different shapes, as the skilled person may envisage. By providing at least three legs 16, the stability of the fetal chamber 100 can be ensured.
In a more preferred embodiment, and as shown in Fig. 1 the fetal chamber 100 further comprises a pressure sensor 34. The pressure sensor 34 may be of any type of pressure sensor, such as strain gauge sensors, a capacitive sensor, a piezoelectric sensor or a Micro-Electro-Mechanical System (MEMS) sensor.
The pressure sensors 34 may be integrated into the legs 16 or into any other supporting means and be used to weigh the fetus and/or the contents of the fetal chamber 100. By measuring the pressure exerted on each leg 16 or supporting means, the pressure sensors 34 can calculate the total weight of the fetal chamber's 100 contents, providing useful data for monitoring the condition and development of the fetus, as well as defining medication guidelines.
In another preferred embodiment of the first aspect of the invention and as shown in Fig. 1, the amniotic fluid circuit further comprises one or more input fluid bags 19.
Advantageously, having one or more input fluid bag 19 allows for the introduction of amniotic fluid into the amniotic fluid circuit when required, for example to perform a full replacement of the amniotic fluid, or to compensate amniotic fluid losses produced by debris suction probes removing the amniotic fluid, or amniotic fluid that the fetus may absorb as it matures within the fetal chamber 100.
Preferably, the input fluid bag 19 may further comprise an additional filter 20, preferably an antibacterial filter. This further ensures the amniotic fluid provided by the input fluid bag 19 into the amniotic fluid circuit is free from bacteria.
Alternatively, or additionally, the amniotic fluid circuit further comprises one or more output fluid bags 21.
Advantageously, having one or more output fluid bag 21 allows for the extraction of amniotic fluid from the amniotic fluid circuit when required, such as during a full replacement of the fluid, or to compensate for the fluid excess that may occur as the fetus matures within the fetal chamber 100.
In another preferred embodiment of the first aspect of the invention and as shown in Figs. 2, 16, 17, 18, and 19, the fetal bed 7 comprises umbilical cord protection means 72. The umbilical cord protection means 72 are comprised in the face of the fetal bed 7 configured to contact the fetus, and are configured to avoid the accidental rupture or disengagement of the connection means from the umbilical cord vessels of the fetus. In this way the provision of umbilical cord protection means 72 further prevents accidents that may lead to a bad development or death of the premature mammalian fetus.
Moreover, the umbilical cord protection means 72 prevents bleeding problems, disconnection problem between the umbilical cord and one of the connection means, by generating a safe area for the umbilical cord.
Also, as the umbilical cord protection means 72 are comprised in the fetal bed 7, when the fetal chamber 100 is opened and the first section 110 and the second section 120 get separated, the umbilical cord protection means 72 ensures the umbilical cord connection remains safe. Thus, the umbilical cord protection means 72, provides additional security to the umbilical in case the fetal chamber 100 has to be opened during the fetal maturing process for any reason.
It is noted that while the umbilical cord protection means 72 of Figs. 2, 16, 17, 18, and 19 has a particular shape, the skilled person may envisage many other alternative to the umbilical cord protection means 72 according to the needs of the fetus.
In a particular embodiment, the premature mammalian fetus is a human fetus.
All of the above are fully within the scope of the present disclosure, and are considered to form the basis for alternative embodiments in which one or more combinations of the above described features are applied, without limitation to the specific combination disclosed above.
In light of this, there will be many alternatives which implement the teaching of the present disclosure. It is expected that one skilled in the art will be able to modify and adapt the above disclosure to suit its own circumstances and requirements within the scope of the present disclosure, while retaining some or all technical effects of the same, either disclosed or derivable from the above, in light of his common general knowledge in this art. All such equivalents, modifications or adaptations fall within the scope of the present disclosure.

CLAUSES

1. A system for maturing a premature mammalian fetus, the system comprising:
1. i. A fetal chamber (100) comprising:
  1. i. A first section (110) comprising:
    1. 1. a first rigid frame (5),
    2. 2. an elastic film (1) comprising at least one fluid inlet port (2a,2b); and
    3. 3. a first sealing means (3),
  2. ii. a second section (120) comprising:
    1. 1. a second rigid frame (10),
    2. 2. a fetal bed (7), comprising at least one fluid outlet port (71) and
    3. 3. a second sealing means (73);
  3. iii. a connection area (17) comprising at least one opening (171);
  wherein the first (110) and second (120) sections have an open position where a premature mammalian fetus can be placed within the fetal chamber, and a closed position where a plurality of latches (12, 15) is configured to create a fluid-tight seal between the first (3) and second sealing means (73) to retain the fetal chamber (100) in a closed, fluid tight configuration; and
2. ii. an amniotic fluid circuit configured to provide an amniotic fluid to and from the fetal chamber (100), the amniotic fluid circuit comprising:
  1. i. an amniotic fluid unit (200) configured to sterilise the amniotic fluid, and
  2. ii. a pump (22) configured to pump the amniotic fluid from the at least one fluid outlet port (71) into the amniotic fluid unit (200) and out from the amniotic fluid unit into the at least one fluid inlet port (2a, 2b).
2. The system according to clause 1, wherein the fetal chamber (100) further comprises means (75) for preventing the formation of pressure ulcers in the premature mammalian fetus.
3. The system according to clause 2, wherein the means (75) for preventing the formation of pressure ulcers are located on the external side of the fetal bed (7).
4. The system according to any one of clauses 2 or 3, wherein the means (75) for preventing the formation of pressure ulcers comprises a mattress.
5. The system according to any one of clauses 1 to 4, wherein the fetal bed (7) comprises umbilical cord protection means (72).
6. The system according to any one of clauses 1 to 5, wherein the fetal chamber (100) further comprises a bed frame (9) between the fetal bed (7) and the second rigid frame (10), wherein the bed frame comprises at least two handles (91) configured to facilitate the manipulation of the fetal bed (7).
7. The system according to any one of clauses 1 to 6, wherein the fetal chamber (100) further comprises one or more additional latches (12) configured to further retain the fetal chamber (100) in a closed, fluid tight configuration at the connection area (17) when a connection means is placed through the at least one opening (171).
8. The system according to any one of clauses 1 to 7, wherein the fetal chamber (100) further comprises flexible adapter means (6) configured to further retain the fetal chamber (100) in a closed, fluid tight configuration at the connection area (17) when a connection means is placed through the at least one opening (171).
9. The system according to clause 8, wherein the fetal chamber (100) further comprises at least one transversal rigid element (8) at the connection area (17) configured to further retain the fetal chamber (100) in a closed, fluid tight configuration at the connection area (17) when a c means is placed through the at least one opening (171).
10. The system according to any one of clauses 1 to 9, wherein the first rigid frame (5) further comprise an opening (51) and the second rigid frame (10) further comprises an opening (104) in the connection area (17), and wherein the fetal chamber (100) further comprises a light source means (18) configured to illuminate the connection area (17) through said openings (51, 104).
11. The system according to any one of clauses 1 to 10, wherein the amniotic fluid unit (200) comprises at least one filter (23,24), wherein the filter (23,24) is a physical filter.
12. The system according to any one of clauses 1 to 11, wherein the amniotic fluid unit (200) comprises an antibacterial filter (25) and/or an antiviral filter (26).
13. The system according to any one of clauses 1 to 12, wherein the amniotic fluid unit (200) comprises an UV treatment unit (27).
14. The system according to any one of clauses 1 to 13, wherein the amniotic fluid unit (200) is further configured to heat the amniotic fluid and the amniotic fluid unit (200) further comprises a heating unit (27).
15. The system according to any one of clauses 1 to 14, wherein the amniotic fluid circuit further comprises at least one sensor configured to monitor the amniotic fluid, the at least one sensor selected from the following list: a contamination sensor (33), a flow, air and/or bubble sensor (31), and/or a temperature sensor (32).
16. The system according to any one of clauses 1 to 15, wherein the fetal chamber (100) further comprises at least one outlet debris port (71).
17. The system according to any one of clauses 1 to 16, wherein the first (110) and second sections (120) can move between the open and closed position through a hinge (11), and wherein the hinge comprises a quick-release mechanism.
18. The system according to any one of clauses 1 to 17, wherein the elastic film (1) further comprises an air outlet (2a,2b).
19. The system according to any one of clauses 1 to 18, wherein the first section (110) further comprises a film frame (4) between the first sealing means (3) and the elastic film (1), configured to further retain the fetal chamber (100) in a closed, fluid-tight configuration.
20. The system according to clause 19, wherein the first section (110) further comprises a second film frame (4'), between the first sealing means (3) and the elastic film (1), configured to form a tongue and groove joint in combination with the first film frame (4) to further retain the fetal chamber (100) in a closed, fluid tight configuration.
21. The system according to any one of clauses 1 to 20, wherein the fetal bed (7) comprises one or more of the following materials: an elastomer and/or silicone
22. The system according to any one of clauses 1 to 21, wherein the second rigid frame (10) further comprises three or more legs (16).
23. The system according to clause 22, wherein the fetal chamber (100) further comprises a pressure sensor (34).
24. The system according to any one of clauses 1 to 23, wherein the amniotic fluid circuit further comprises one or more input fluid bags (19) and/or output fluid bags (21).

Claims

A system for maturing a premature mammalian fetus, the system comprising:
a. A fetal chamber (100) comprising:
i. A first section (110) comprising:
1. a first rigid frame (5),

2. an elastic film (1) comprising at least one fluid inlet port (2a,2b); and

3. a first sealing means (3),

ii. a second section (120) comprising:
1. a second rigid frame (10),

2. a fetal bed (7), comprising at least one fluid outlet port (71) and

3. a second sealing means (73);

iii. a connection area (17) comprising at least one opening (171);
wherein the first (110) and second (120) sections have an open position where a premature mammalian fetus can be placed within the fetal chamber, and a closed position where a plurality of latches (12, 15) is configured to create a fluid-tight seal between the first (3) and second sealing means (73) to retain the fetal chamber (100) in a closed, fluid tight configuration; and

b. an amniotic fluid circuit configured to provide an amniotic fluid to and from the fetal chamber (100), the amniotic fluid circuit comprising:
i. an amniotic fluid unit (200) configured to sterilise the amniotic fluid, and

ii. a pump (22) configured to pump the amniotic fluid from the at least one fluid outlet port (71) into the amniotic fluid unit (200) and out from the amniotic fluid unit into the at least one fluid inlet port (2a, 2b).
The system according to claim 1, wherein the fetal chamber (100) further comprises means (75) for preventing the formation of pressure ulcers in the premature mammalian fetus wherein the means (75) for preventing the formation of pressure ulcers are located on the external side of the fetal bed (7).
The system according to claim 2, wherein the means (75) for preventing the formation of pressure ulcers comprises a mattress.
The system according to any one of claims 1 to 3, wherein the fetal bed (7) comprises an umbilical cord protection means (72).
The system according to any one of claims 1 to 4, wherein the fetal chamber (100) further comprises a bed frame (9) between the fetal bed (7) and the second rigid frame (10), wherein the bed frame comprises at least two handles (91) configured to facilitate the manipulation of the fetal bed (7).
The system according to any one of claims 1 to 5, wherein the fetal chamber (100) further comprises one or more additional latches (12) configured to further retain the fetal chamber (100) in a closed, fluid tight configuration at the connection area (17) when a connection means is placed through the at least one opening (171).
The system according to any one of claims 1 to 6, wherein the fetal chamber (100) further comprises flexible adapter means (6) configured to further retain the fetal chamber (100) in a closed, fluid tight configuration at the connection area (17) when a connection means is placed through the at least one opening (171).
The system according to any one of claims 1 to 7, wherein the fetal chamber (100) further comprises at least one transversal rigid element (8) at the connection area (17) configured to further retain the fetal chamber (100) in a closed, fluid tight configuration at the connection area (17) when a connection means is placed through the at least one opening (171).
The system according to any one of claims 1 to 8, wherein the first rigid frame (5) further comprise an opening (51) and the second rigid frame (10) further comprises an opening (104) in the connection area (17), and wherein the fetal chamber (100) further comprises a light source means (18) configured to illuminate the connection area (17) through said openings (51, 104).
The system according to any one of claims 1 to 9, wherein the amniotic fluid unit (200) comprises at least one filter (23,24), wherein the filter (23,24) is a physical filter.
The system according to any one of claims 1 to 10, wherein the amniotic fluid unit (200) comprises an antibacterial filter (25) and/or an antiviral filter (26).
The system according to any one of claims 1 to 11, wherein the amniotic fluid unit (200) comprises an UV treatment unit (27).
The system according to any one of claims 1 to 12, wherein the amniotic fluid unit (200) is further configured to heat the amniotic fluid and the amniotic fluid unit (200) further comprises a heating unit (27).
The system according to any one of claims 1 to 13, wherein the amniotic fluid circuit further comprises at least one sensor configured to monitor the amniotic fluid, the at least one sensor selected from the following list: a contamination sensor (33), a flow, air and/or bubble sensor (31), and/or a temperature sensor (32).
The system according to any one of claims 1 to 14, wherein the fetal chamber (100) further comprises at least one outlet debris port (71).