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The present invention relates to the breath sampling field, and in particular is a medical device for sampling the air contained in the last respiratory tract, called in the jargon: "End-Tidal".

It is a main object of the device according to the invention, which will be referred to below as "sampler", to allow the doctor or the operator to collect two types of samples on two cartridges: a first cartridge Cp, on which the alveolar breath of a patient is collected, and a second cartridge Ca, containing the air of the environment in which the sampling is carried out.

According to the present invention, it is contemplated that once the acquisition step is completed, the two cartridges are sent to a specialized laboratory to be analyzed. The output of the analysis at the laboratory - appropriately anonymous - is automatically sent to the doctor who performed the examination and simultaneously uploaded to a remote database. The latter database collects data from all devices anonymously.

The process is structured as follows:

1. The patient goes to the sampling point (hospital, pharmacy, etc.), authorizing the medical staff to process his/her personal data;

2. The doctor prepares, within the device, the disposable components (nozzles and cartridges) which will be used for each patient and turns the device on;

3. The device automatically performs a purging procedure which allows cleaning of the device, ensuring greater reliability of the acquisition;

4. The doctor makes a medical history of the patient entering all the data concerning the patient's health status in the software;

5. The patient undergoes the examination by exhaling through a disposable mouthpiece present on the sampler;

6. The device collects the breath and ambient air samples on the cartridges Cp and Ca, respectively;

7. Once the analysis has been completed, the software allows the doctor to print the QR-Code identifying the sample, which is then applied to the cartridges ;

8. The two cartridges are sent to a specialized assay laboratory;

9. The laboratory analyzes the cartridges (without any reference to the patient's sensitive data), sends its report to the center where the sampling was carried out and uploads it to a remote centralized database;

10. The doctor displays the laboratory report and makes the diagnosis.

OPERATING PRINCIPLE

In order to collect only the breath belonging to the desired alveolar tract on the Cp cartridge, there are adequate volume buffers to the patient, such as 200 ml for adults, lower for children. The patient is asked to make, through a disposable mouthpiece, several deep expirations within the device: according to the invention, it is contemplated that the first part of the breath expelled by the patient passes through the device and exits therefrom; the last part of the breath, instead, remains collected within said buffers .

At this point, the solenoid valves inside the sampler are closed and a suction pump P is activated to cause the passage of air contained in the buffers through the first cartridge Cp and the consequent entrapment of the volatile organic compounds on the adsorbent bed contained in the cartridge itself. This mode of operation allows, asking the patient to exhale alternately in the two disposable mouthpieces, the two buffers B1 and B2 to be filled with breath: the device is configured so that the pump P, once activated, empties the buffer B1 first and then the buffer B2, pouring the contents into the cartridge Cp.

Advantageously, the sampler according to the present invention does not require medical air sources to be inhaled by the patient: the latter is required only to exhale inside the device.

The sections of the device in which the air exhaled by the patient flows are brought, through a specially designed heating system, to a temperature which prevents the formation of condensation which could compromise the assay (since the adsorbent materials of the cartridges are water-repellent, they prevent the formation of condensation inside the cartridges). For this purpose, a temperature sensor is also provided which is configured for measuring, at fixed time intervals, the temperature and for sending the measured value to a mini PC set up inside the sampler itself. Depending on the temperature detected, the mini PC automatically turns the heating system on or off.

As regards the second cartridge Ca, intended for ambient air, said solenoid valves are configurable (as will be seen hereafter) so as to allow, through the action of the pump P, the air intake of the surrounding environment in order to make it flow into the cartridge Ca.

The volume of breath and ambient air sent to the respective cartridges is instead determined by means of a flow meter F.

The device is managed by the user (doctor, technician, etc.) through its graphical interface, after proper two-factor authentication:

1. Software, through access credentials, to be entered on a graphical interface;

2. Hardware, via an authorized USB flash drive, to be connected to the sampler.

At the end of the acquisition, the system allows printing two copies of an identifying QR Code for the two cartridges Cp and Ca to be applied onto the same to send them to the assay center with an appropriate laboratory.

For each patient, the device provides a local encrypted database on which all useful (sensitive) data can be saved in order to identify the patient, his/her medical history and all the information related to the sampling performed. Once the two cartridges Cp and Ca have been received, identified by said anonymous QR codes with respect to the sensitive data of the sampled patients, the laboratory carries out the assay and, through an ad hoc software, sends his/her report to the remote database and simultaneously sends a notification (preferably by email) to the hospital center of origin of the cartridges. In this way, through the synchronization of the sampler via the internet, the doctor has the opportunity to view the report provided by the laboratory (and then proceed with his/her diagnostic procedure) and the remote database, at the same time, gradually populates an increasing amount of data.

The sampling device 1 according to the invention provides a pneumatic circuit comprising (figure 1):

• VI, V2, V3, V4 = 2-way solenoid valves

• V5, V6 = 3-way solenoid valves

• Cp = patient cartridge

• Ca = ambient air cartridge

• P = suction pump

• F = flow meter

• Bl, B2 = buffer

The volume of each buffer is preferably not greater than 200 ml, because this is the volume of alveolar tract which is expected to be sampled.

The main functions related to the operating steps are:

I - Ambient air acquisition:

The solenoid valves inside the device VI and V3 are closed and the solenoid valves V2 and V4 are open: the valve V5 is configurable to open one channel first and then another, so as to allow the pump P to suck in air from outside and send it to the cartridge Ca, making it pass first through buffer B1 and then through buffer B2

The solenoid valve V6 is configured for connecting the pump P to the cartridge Ca.

·/ The suction pump P is activated and remains in the ON state until, through the feedback of the flow meter F, it is calculated that the required volume of air has been sent onto the cartridge Ca (Fig. 4)

The ambient air enters the device through the solenoid valves V2 and V4 and passes through the buffers B1 and B2.

It is preferable to first acquire the ambient air in the cartridge Ca and then the patient’s breath in the cartridge Cp: in this way, the ambient air is not contaminated by the patient's breath.

II - Acquisition of the patient's breath:

The patient exhales inside the sampling device 1 The bronchial breath (first respiratory tract) passes through the inlet valves Vl-VB, passes through the buffers B1-B2 and exits the outlet valve (V2-V4) of the sampling device 1, while the alveolar portion is collected inside buffers Bl- B2, which have a volume equal to the average value estimated for the alveolar section (Fig. 2)

s Through the suction pump P, the air contained in the buffers B1-B2 is conveyed onto the cartridge Cp. In fig. 3, the transfer of breath from buffer B1 is indicated, but the same procedure is also applied to buffer B2, in fact the patient is asked to exhale in the disposable mouthpiece connected to valve V3, filling the buffer B1 and then to exhale first into the disposable mouthpiece connected to valve VI, filling the buffer B2.

The process is reiterated until the desired amount of breath is made to pass through the cartridge Cp (Fig. 3)

The solenoid valve V5 may be configured to first open one channel and then another, so as to allow the pump P to first empty the buffer B1 and then the buffer B2, causing the breath to flow from one or the other buffer;

The solenoid valve V6, instead, is placed between the pump P and the cartridges, and is configured - in this case - to put in communication the cartridge Cp and the pump itself.

It is preferable to provide two separate mouthpieces for different reasons:

• Decrease the execution time of the examination (in fact, in this way, by means of software, with single keys it is possible to double the breath brought into to cartridge: one for each cartridge)

• Have a backup line, if one stops working

• Being able to connect one buffer to the sensor line and the other to a cartridge

• In the case in which a single mouthpiece is provided, connected to the two buffers by a 3-way valve upstream of the two buffers, there would be some bends in the pipes which are not acceptable because each bend increases the impedance (resistance due to losses of the air flow load) detected by the patient when he/she exhales; by providing two independent lines, on the other hand, this phenomenon has been reduced and the effect of having two totally independent lines has also been obtained.

Ill - Purging of the device:

The authorized user replaces the two cartridges Ca and Cp with two tubes (supplied with the device) of the same size as the cartridges which allow the pneumatic circuit to be closed

· In this case, the solenoid valves V1-V2-V3-V4 are open and the valves V5 and V6 change continuously and alternately 0N-0FF status (open-closed) in order to make air flow in all the conduits of the pneumatic circuit inside the device

s The suction pump P is activated and remains in the ON status for a certain time, in order to allow the passage of the ambient air in all the branches of the device and then carry out a purge of the device (the air flow is as indicated for the acquisition of ambient air)

According to a peculiar feature of the present invention, the two cartridges Ca and Cp present in the device allow detecting the differences between the ambient air, also breathed by the patient, and the exhaled of the patient himself, so as to be able to determine if a contamination is present in ambient air or is due to a patient's pathology. The pneumatic circuit described thus far is managed/controlled by an electrical interface as shown in Figure 5, where:

• VI, V2, V3, V4, V5, V6 = solenoid valve

• P = suction pump

• F = flow meter

• H = heating element

• T = temperature sensor

• Power supply outside the device

The graphical interface of the device user software - which can only be managed by authorized personnel - consists preferably of five main pages, shown as examples in figures 6 to 10:

• Home page: welcome page of the device (figure 6)

• Patient data: allows viewing, modifying or deleting one or more patients already present in the local database of the device, or adding new ones; By selecting a patient already entered, it is possible to view the list of samplings which have been already done (figure 7)

• Breath Acquisition (figure 8) allows:

o selecting the patient to be sampled

o entering data related to sampling

o managing the various acquisition steps of the device

o checking, by means of an LED, whether the temperature inside the device allows the examination to be carried out or not

o checking, by means of an LED, whether the acquisition of the breath sample is finished or not o generating, at the end of the examination, a label (in PDF format) to be printed and applied on the cartridges: such a label contains a QR Code showing some details about the sampling done.

• Service (figure 9): the sampler autonomously and cyclically checks the correct functioning of all its components and indicates any anomalies to the user through green or red LEDs. The management/support of the device may also be carried out remotely due to the presence of two keys which allow to enable/disable the remote connection of a user provided with access credentials to the device.

• Cloud Data Sync (figure 10): after entering the authentication credentials, the device, if connected to an internet network, through a secure connection, synchronizes the local database with the remote one.

According to a peculiar feature of the present invention, the Cloud Data Sync is also configured to save data anonymously on a single remote DB; this feature allows carrying out - for example epi demi ol ogi cal i nvesti gati ons .

Based on the foregoing, the device according to the present invention consists substantially of the following main components:

• External body: external part of the device, made of plastic material with the following provisions:

o holes for the disposable mouthpiece connections o side handles to facilitate the patient's grip on the device

o power button

o connector for the power supply of the device o LED panel: contains LEDs indicating the operating status of the device

• Sterile disposable mouthpieces: made of plastic material and provided with check valves allow the patient to exhale inside the device;

• Cp cartridge: stainless steel cartridge containing an appropriate adsorbent bed on which the substances contained in the air exhaled by the patient are collected;

• Cartridge Ca: stainless steel cartridge containing an appropriate adsorbent bed on which the substances contained in the ambient air are collected;

• Solenoid valves: allow the flow of exhaled air to be guided inside the ducts, according to the operating step of the device;

• Heating system: useful to achieve, within the device, the optimal temperature to perform the examination;

• Temperature sensors: allow monitoring of the temperature inside the device and consequently controlling the heating system;

• Flow sensor: necessary to calculate the volume of breath collected on the cartridges;

• Suction pump: useful to suck the air either from the outside towards the cartridge Ca or from the buffers towards the cartridge Cp;

• Power supply; • Mini PC: it contains the management software of the device and generates the Wi-Fi Hotspot to which the personnel in charge of carrying out the examination is connected via external devices;

• Interface card: an electronic card which powers the whole system and allows connecting the Mini PC to the sensors and actuators;

• Pneumatic fittings: ducts through which the air exhaled by the patient and the ambient air flow;

• Buffer of inert material and variable volume: two single-use sachets in which the alveolar breath remains before it is brought onto the cartridge Cp. The size of these buffers varies according to the age of the patients: larger sachets for adults, smaller for children.

In figure 11 the system architecture is shown.

It should be noted that the process illustrated herein would be equally valid if the data collected by the sampler were transmitted to the assay laboratory by any other means (e.g. mail, paper mail, certified e-mail, etc.), ensuring in any case the anonymity of the patient’s data.

Within the device it is possible to integrate an additional acquisition line useful for analyzing in real time the sample of alveolar exhalation with an array of sensors. These sensors can, for example, be used either to verify the reproducibility of the acquisition of the exhaled sample or for diagnostic purposes, by measuring the amount of a given target molecule within the breath. The extended product architecture is therefore shown in Figure 12, where: • VI, V2, V3, V4 = 2-way solenoid valves

• V5, V6, V7 = 3-way solenoid valves

• Cp = patient cartridge

• Ca = ambient air cartridge

· P = suction pump

• F = flow meter

• Bl, B2 = buffer

• S = sensor array

The wiring diagram thus becomes that shown in figure 13, where:

• VI, V2 , V3 , V4, V5 , V6, V7 = solenoid valve

• P = suction pump

• F = flow meter

• H = heating element

· T = temperature sensor

• S = sensor array

• Power supply preferably, but not exclusively, outside the device.