Patent Description:
Physical contact with newborns residing in neonatal incubators, especially by persons other than the newborn's mother, should be avoided as much as possible, as such contact may cause the newborn stress and/or expose it to contaminants. Placing a newborn in an incubator may create an opportunity to employ minimally-invasive techniques, such as gas analysis. However, existing gas analysis techniques for diagnosing neonatal disease, while less invasive than other techniques (e.g., obtaining blood samples), still require physical contact with the newborn, e.g., to position a gas mask over the newborn's mouth and nose and/or to insert air tubes into the newborns nostrils. Thus, there is a need in the art to provide a less-invasive, and preferably non-invasive, way to perform gas analysis of a newborn's exhaled breath, as well as of the newborn's skin, feces and/or urine.

<CIT> discloses a system for monitoring an exhaled breath of a subject. <CIT> discloses a device for measurement of breath VOCs which uses a spectroscopy unit. <CIT> discloses gas chromatograph. "<NPL>) discloses analysis of gas in an incubator chamber to observe the effect of an inserted hand after hand sanitization. Analyzing the emission of VOCs from medical equipment inside a neonatal incubator is disclosed in <NPL>. Document <CIT> discloses a neonatal incubator with a humidity sensor and oxygen cells. Document <CIT> discloses a neonatal incubator with an alarming means responsive to the opening and closing of the doors of the incubator.

The present disclosure is directed to methods and apparatuses for non-invasive neonatal gas analysis. For example, in various embodiments, a neonatal gas analysis apparatus may be configured to obtain one or more samples of gas from an interior of a neonatal incubator. These samples may contain various types of molecules of interest, such as biomolecules, carbohydrates, volatile organic compounds ("VOCs"), etc., that may be carried in an infant's breath, feces, skin, and/or urine. The neonatal gas analysis apparatus may isolate, capture, and/or concentrate one or more types of molecules from the one or more gas samples, and analyze the isolated, captured and/or concentrated biomolecules to determine one or more health indicators associated with an infant residing in the neonatal incubator.

Physical contact with newborns residing in neonatal incubators, especially by persons other than the newborn's mother, should be avoided as much as possible, as such contact may cause the newborn stress. Existing techniques for diagnosing neonatal disease using gas analysis, while less invasive than other techniques, still require physical contact with the newborn. Accordingly, Applicants have recognized and appreciated that it would be beneficial to provide a less-invasive, and preferably non-invasive and unobtrusive, way to perform gas analysis of an incubated neonatal. In view of the foregoing, various embodiments and implementations of the present disclosure are directed to a neonatal gas analysis apparatus.

Referring to <FIG>, in one embodiment, a neonatal incubator <NUM> (hereinafter, simply "incubator") may including a housing <NUM> that may be transparent, translucent, or even opaque. In various embodiments, incubator may define an interior <NUM> that may be a suitable environment for caring for an ill or premature newborn infant <NUM>. While apparatus, systems, and methods described herein refer to "neonatal" incubators for humans, that is not meant to be limiting. Various techniques and apparatus described herein may be applied elsewhere, such as incubators for animals, or in other medically-protective environments such as negative pressure ventilators (e.g., "iron lungs").

In various embodiments, housing <NUM> may define various openings or ports that provide an interface between interior <NUM> and an exterior environment in which incubator <NUM> is placed (e.g., in a neonatal intensive care unit, or "NICU"). For example, two hand-insertion portals, 108a and 108b, may be provided to permit medical personnel and/or a relative of infant <NUM> (e.g., parents) to reach into interior <NUM> to perform various actions, such as taking medical measurements (e.g., blood pressure, blood samples), or simply to caress infant <NUM> with human touch. In some embodiments, portals 108a and 108b may be sealed with integral gloves (not depicted) to ensure that the person reaching into interior <NUM> of incubator <NUM> does not expose interior <NUM> to germs. In other embodiments, portals 108a and 108b may be selectively opened and closed, as needed, using various mechanisms.

In various embodiments, incubator <NUM> may be equipped with a neonatal gas analysis apparatus <NUM>. In various embodiments, neonatal gas analysis apparatus <NUM> may include a gas sampler <NUM> configured to obtain one or more samples of gas from interior <NUM> of incubator <NUM>. Gas sampler <NUM> may obtain samples of various sizes, depending on the circumstances, and may take multiple samples at various frequencies, also depending on the circumstances. In some embodiments, gas sampler <NUM> may include a pump (not depicted) and pump controller (also not depicted) that may be operated to control parameters of the pump's operation, such as the volume of gas sampled, the frequency at which gas is sampled, etc. In some embodiments, passive gas sampling may be employed, e.g., by placing a sorbent material in interior <NUM> for a predetermined amount of time.

In various embodiments, neonatal gas analysis apparatus <NUM> may also include a gas analyzer <NUM> that is in direct or indirect gaseous communication with gas sampler <NUM>. In various embodiments, gas analyzer <NUM> may be configured to analyze one or more types of molecules contained in gas samples obtained by gas sampler <NUM>, and to provide one or more signals of one or more health indicators based on the analysis. For example, in various embodiments, gas analyzer <NUM> may be configured to identify levels of one or more types of molecules contained in gas samples obtained by gas sampler <NUM>.

A variety of types of molecules, such as biomolecules, carbohydrates, and/or volatile organic compounds ("VOCs") that might be found within an incubator may be analyzed by gas analyzer <NUM>. These may include but are not limited to acetone, acetaldehyde, octadecane, nitrogen-containing VOCs such as acetamide or ammonia, sulfur-containing VOCs such as carbon disulfide, and/or ethers such as dimethyl ether or diethyl ether. Additionally or alternatively, straight chain alkenes may be analyzed, including methane, ethane, propane, butane, pentane, hexane, heptane, and/or octane. Additionally or alternatively, branched chain alkanes such as <NUM>-methylpropane or methylbutane may be analyzed. In some embodiments, alkynes and/or non-cyclic alkenes such as propene or <NUM>-Butene <NUM>-Butene <NUM>-Pentene may be analyzed. Additionally or alternatively, in various embodiments, one or more of the following may be analyzed by gas analyzer <NUM>: benzyl and phenyl hydrocarbons, non-aromatic cyclic hydrocarbons, other hydrocarbons, alcohol volatiles, aldehyde volatiles, primary aliphatic acid volatiles, branched aliphatic acid volatiles, unsaturated acid volatiles, carboxylic acid volatiles, acetic acid esters, straight chain aliphatic acid esters, branched and cyclic aliphatic acetic acid esters, aromatic carboxylic acid esters, cyclic esters, other esters, non-cyclic alkenes (multiple double bonds), straight chain aliphatic ketones, branched chain and cyclic aliphatic ketones, di-ketones, unsaturated ketones, other ketones, and/or halogen containing VOCs. In some embodiments, gas analyzer <NUM> may identify when levels of bilirubin reach a threshold by measuring amounts of carbon monoxide production by infant <NUM>, which at high enough levels can cause jaundice.

Gas analyzer <NUM> may be configured to provide, based on its analysis of gas samples obtained by gas sampler <NUM>, a wide variety of health indicators pertaining to infant <NUM>. In some embodiments, gas analyzer <NUM> may provide information about diseases such as bacterial infection. In some embodiments, gas analyzer <NUM> may provide information about VOCs found in exhaled breath, skin, urine and/or feces, which could be used to diagnose heath issues and/or to notify health personnel that infant <NUM> requires a change of diaper. In some embodiments, gas analyzer <NUM> may be configured to provide, based on its analysis, indicators of necrotizing enterocolitis ("NEC"), bronchopulmonary dysplasia ("BPD"), and/or pneumonia.

In some implementations, neonatal gas analysis apparatus <NUM> may include a preconditioner <NUM> in direct or indirect gaseous communication with gas sampler <NUM>. In various embodiments, preconditioner <NUM> may be configured to "precondition" one or more gas samples obtained by gas sampler <NUM> to be in a state that is suitable for analysis by gas analyzer <NUM>. For example, in various embodiments, preconditioner <NUM> may capture, isolate, and/or concentrate one or more types of molecules from one or more gas samples obtained by gas sampler <NUM>.

In some embodiments, preconditioner <NUM> may include one or more surfaces (e.g., beads) treated with a sorbent (e.g., an adsorbent or absorbent). The sorbent may be configured, e.g., through absorption or adsorption, to capture and/or concentrate one or more types of molecules, such as one or more carbohydrates. In such embodiments, gas analyzer <NUM> may be configured to analyze the captured and concentrated one or more types of molecules.

In some embodiments, preconditioner <NUM> may include a temperature regulator (not depicted, may include, for instance, a heating element with a controller such as a thermostat) configured to alter a temperature of the one or more samples of gas obtained by gas sampler <NUM>. The temperature regulator may be activated to increase and/or decrease a temperature of the gas samples collected by gas sampler <NUM>, and/or to increase and/or decrease a temperature of captured and concentrated targeted types of molecules (e.g., in a sorbent material), in order to release the one or more targeted types of molecules.

In some embodiments, preconditioner <NUM> may be configured to concentrate gas sampled by gas sampler <NUM> by causing gas sampler <NUM> to sample for a predetermined time interval. In some embodiments, preconditioner <NUM> may cause gas samples captured by gas sampler <NUM> to be at a suitable flow and/or pressure, e.g., by compressing gas sampled by gas sampler <NUM> over such a predetermined time interval. Additionally or alternatively, in some embodiments, preconditioner <NUM> may be configured to remove various components from gas sampled by gas sampler <NUM>. For example, in some embodiments, preconditioner <NUM> may remove water, e.g., in the form of humidity and/or water vapor, from gas sampled by gas sampler <NUM>.

In various embodiments, one or more components of neonatal gas analysis apparatus <NUM>, such as gas analyzer <NUM>, may be communicatively coupled with one or more computing systems, such as server <NUM> in <FIG>, via a communication link <NUM>. Various wired or wireless communication technologies may be used to implement communication link <NUM>, including but not limited to The Institute of Electrical and Electronics Engineers ("IEEE") <NUM> standard (Ethernet), the IEEE <NUM> standard (Wi-Fi), Bluetooth, radio frequency identification ("RFID"), coded light, and so forth. In various embodiments, server <NUM> may be configured to provide, e.g., to a remote computing device <NUM> over one or more communication links <NUM>, data configured to enable remote computing device <NUM> to provide a user interface <NUM>, as well as data indicative of the one or more signals of one or more health indicators provided by gas analyzer <NUM>. User interface <NUM> may in turn provide output indicative of the one or more health indicators, such as charts, graphs, tables, numerical values, warnings (e.g., audible or visual), and so forth. Communication link <NUM> may be implemented using the same technology as communication link <NUM>, and/or using a different technology.

In some embodiments, server <NUM> may be in communication with a plurality of neonatal gas analysis apparatus <NUM> installed on a plurality of incubators <NUM>. In such a scenario, server <NUM> may be configured to provide health indicators and/or other data to remote computing devices (e.g., <NUM>) about multiple neonatal incubators, e.g., across a NICU. In other embodiments, neonatal gas analysis apparatus <NUM> may communicate directly with one or more remote computing devices (e.g., <NUM>), without an intermediate server. In some embodiments, neonatal gas analysis apparatus <NUM> may include an integral user interface, e.g., a touch screen display mounted on housing <NUM>, that enables a user to directly control and/or obtain heath indicators from neonatal gas analysis apparatus <NUM>.

In some embodiments, a reliability indicator <NUM> may be in communication with one or more components of neonatal gas analysis apparatus <NUM>, such as gas analyzer <NUM>, over a communication link <NUM>. Communication link <NUM> may be implemented using the same or different technologies as communications links <NUM> and/or <NUM>. In some embodiments, reliability indicator <NUM> may be implemented as any combination of hardware and software, and could include, for instance, a field-programmable gate array ("FPGA") and/or an application-specific integrated circuit ("ASIC"). However reliability indicator <NUM> is implemented, it may be operably (e.g., electrically) coupled with one or more sensors (not depicted) that detect when one or more openings of incubator <NUM> (e.g., portals 108a and 108b) have been opened.

Based on this detection, reliability indicator <NUM> may be configured to provide, to gas analyzer <NUM>, based on a state of isolation between interior <NUM> of incubator <NUM> and an exterior environment, a signal indicative of reliability of the one or more samples of gas obtained by gas sampler <NUM>. For example, in some embodiments, reliability indicator <NUM> may provide gas analyzer <NUM> with a signal indicative of a passage of time since interior <NUM> of neonatal incubator <NUM> was exposed to the exterior environment. Gas analyzer <NUM> may be configured to calculate a measure of accuracy of the one or more signals of the one or more health indicators it provides based on the signal from reliability indicator <NUM>. For example, gas analyzer <NUM> may calculate a measure of accuracy of the one or more signals of the one or more health indicators based on passage of time provided by reliability indicator <NUM>. In some embodiments, if the passage of time since interior <NUM> was exposed to an outside environment fails to satisfy one or more thresholds, gas analyzer <NUM> may disregard and/or discard gas samples from gas sampler <NUM>, and/or may wait until the passage of time since interior <NUM> was exposed to the outside environment satisfies the one or more thresholds before resuming analysis.

In some embodiments, a vital sign unit <NUM> may be in communication with one or more components of neonatal gas analysis apparatus <NUM>, such as gas analyzer <NUM>, via communication link <NUM>. Communication link <NUM> may be implemented using the same or different technologies as previously-mentioned communication links (e.g., <NUM>, <NUM>, <NUM>). Vital sign unit <NUM> may be configured to obtain one or more vital signs, e.g., from infant <NUM>, using various types of invasive, semi-invasive, and non-invasive probes, such as an electrocardiogram. Various vital signs may be obtained, including but not limited to oxygen saturation, signs pertaining to respiration, heart rate, blood pressure, glucose levels, and so forth. In various embodiments, vital sign unit <NUM> may provide, e.g., to gas analyzer <NUM> over link <NUM>, one or more signals indicative of these vital signs. Gas analyzer <NUM> may in turn incorporate these vital signs into its own analysis. For example, in some embodiments, gas analyzer <NUM> may determine that there likely is bacterial infection present based on a combination of increased heart rate, blood pressure, body temperature, and one or more biomarker findings. As another example, sepsis may be detected based on a combination of breath analysis and heart rate variability. In some embodiments, gas analyzer <NUM> may provide data indicative of the vital signs to server <NUM>, so that they may be presented at user interface <NUM> alongside the other health indicators determined from analysis performed by gas analyzer <NUM>.

In some embodiments, an air quality controller <NUM> may be in communication with one or more components of neonatal gas analysis apparatus <NUM>, such as gas analyzer <NUM>, via communication link <NUM>. Communication link <NUM> may be implemented using the same or different technologies as previously-mentioned communication links (e.g., <NUM>, <NUM>, <NUM>, <NUM>). Air quality controller <NUM> may be configured to receive, e.g., directly or indirectly from gas analyzer <NUM> and/or vital sign unit <NUM>, data indicative of various health indicators, vital signs, and/or other conditions within incubator <NUM>. In response to this received data, which air quality controller <NUM> may treat as feedback, air quality controller <NUM> may perform various air quality control measures, such as selectively diverting fresh air <NUM> into interior <NUM> of incubator <NUM>. While not depicted in <FIG>, in various embodiments, one or more filters, sorbent materials, or other air purification mechanisms may be deployed between air quality controller <NUM> and interior <NUM> to reduce and/or eliminate pollutants that might otherwise contaminate interior <NUM>.

In addition to or instead of providing fresh air <NUM>, in some embodiments, air quality controller <NUM> may monitor and/or control other attributes of the environment within interior <NUM> of incubator <NUM> based on data it receives from neonatal gas analysis apparatus <NUM>, such as temperature, humidity, oxygen levels, and so forth. For example, gas analyzer <NUM> may provide data indicating that oxygen within interior <NUM> is too low. In response, air quality controller <NUM> may divert fresh air into interior <NUM> until gas analyzer <NUM> determines that oxygen levels within interior <NUM> are acceptable.

Referring now to <FIG>, an example method <NUM> for monitoring a neonatal incubator (e.g., <NUM>) using gas analysis is depicted. While the operations of method <NUM> are shown in a particular order, this is not meant to be limiting. One or more operations may be added, omitted, or reordered. At block <NUM>, one or more samples of gas may be obtained from an interior (e.g., <NUM>) of an incubator (e.g., <NUM>), e.g., by gas sampler <NUM>. At block <NUM>, the one or more gas samples obtained at block <NUM> may be preconditioned, e.g., by preconditioner <NUM>, to capture, concentrate, and/or isolate one or more types of molecules (examples mentioned above) from the one or gas samples. For example, in some embodiments, and as indicated at block <NUM>, one or more sorbent materials may be used to adsorb one or more targeted types of molecules. In some embodiments, at block <NUM>, a temperature of the gas samples and/or sorbent materials may be altered, e.g., to release one or more targeted types of molecules. In some embodiments, one or more non-targeted components, such as water, may be removed from the gas samples at block <NUM>.

At block <NUM>, one or more vital signs, such as heart rate, temperature, blood pressure, glucose levels, and so forth, may be obtained, e.g., by vital sign unit <NUM>. At block <NUM>, one or more signals pertaining to reliability of the gas samples may be obtained, e.g., from reliability indicator <NUM>. At block <NUM>, the molecules that were captured, concentrated, and/or isolated at block <NUM> may be analyzed, e.g., by gas analyzer <NUM>, e.g., in combination with the vital signals obtained at block <NUM> and/or the reliability signals obtained at block <NUM>.

Claim 1:
A neonatal incubator (<NUM>), comprising:
- a housing (<NUM>) defining an interior (<NUM>) to house a neonate;
- a gas sampler (<NUM>) configured to obtain one or more samples of gas from the interior of the housing;
- a gas analyzer (<NUM>) in at least indirect gaseous communication with the gas sampler and configured to analyze one or more types of biomolecules in the one or more samples of gas that are carried in a neonate's breath, feces, skin and/or urine and provide one or more signals of one or more health indicators associated with the neonate, relating to diseases or health issues, based on the analysis,
wherein the gas analyzer is configured to provide data usable to render a user interface to provide output indicative of the one or more health indicators,
characterized in that
the biomolecules comprise one or more of:
acetone; acetaldehyde; octadecane; nitrogen-containing VOCs;sulfur-containing VOCs; ethers; straight chain alkenes;branched chain alkanes; alkynes and/or non-cyclic alkenes; benzyl and phenyl hydrocarbons; non-aromatic cyclic hydrocarbons; alcohol volatiles; aldehyde volatiles; primary aliphatic acid volatiles; branched aliphatic acid volatiles; unsaturated acid volatiles; carboxylic acid volatiles; acetic acid esters; straight chain aliphatic acid esters; branched and cyclic aliphatic acetic acid esters; aromatic carboxylic acid esters; cyclic esters; non-cyclic alkenes; straight chain aliphatic ketones; branched chain and cyclic aliphatic ketones; di-ketones; unsaturated ketones; halogen containing VOCs; and further characterized in that the neonatal incubator comprises
- a reliability indicator (<NUM>) operably coupled with the gas analyzer and configured to provide, to the gas analyzer, based on a state of isolation between the interior of the housing and an exterior environment, a signal indicative of reliability of the one or more samples of gas.