DESCRIPTION

"PROCESS FOR MONITORING THE SUCCESS OF THE ADMINISTRATION

OF A FLUID TO A NON HETEROGENOUS BIOLOGICAL TARGET, AND

SYSTEM THAT ENABLES THE EXECUTION OF SAID PROCESS"

FIELD OF THE INVENTION

The hereby described invention refers a process for monitoring the success of the administration of a fluid to a non-heterogeneous biological target, for example the instillation of a medical drop to an eye, and a system and device that enables execution of said process, whilst aiding the abovementioned administration action.

BACKGROUND OF THE INVENTION

Generally speaking, physicians have no means to know if their patients have complied with the prescribed therapeutic regimen when said regimen is domestic and ambulatory, since there are no objective methods to determine if a given patient has taken his medicine on the intended days and hours .

In the specific case of Ophthalmology, in which the therapy usually consists of instillable eye drops, the problem is even more complex due to the inherent difficulty of self -administering eye-drops. Due to this there are

already countless devices and methods to aid patients in this administration.

However, although there are numerous devices to aid patients in their self -administration of instillable fluid medicine, or to attempt to validate compliance by monitoring the date and time of events that may cause medical fluid to leave its container, for example fluid container squeezing. There are no solutions that address the part of the problem comprised between the fluid leaving its container and reaching the target .

Due to difficulty of handling the flask, that may include hand shaking common to the elderly, the alignment of the flask and the eye might be compromised, causing the patient to fail at the self -administration of the medicinal fluid regardless of patient's will to cooperate.

Again addressing for example the specific case of Ophthalmology, even when the alignment is correct, the possibility that the patient's eyes might close during the drop's fall and be closed as the fluid reaches their eyes might invalidate the instillation attempt.

In the special case of clinical trials, there is also the issue of user identification, since there might be intentional and malicious non-compliance in attempts to deceive the validation system.

DESCRIPTION OF THE RELATED ART

Existing literature reveals several attempts to aid self -instillation of eye drops. These approaches are invariably related to the creation of structures to position the flask in reference to the patient's eye

(patents US5665079, US5713495, US5611788, among many others) , or devices to simplify the handling of the flask

(OPTICARE ^® , patent WO2004080367) .

In what regards the attempts to validate the correct instillation of the drop, existing approaches rely on recording the date and hour in which the flask containing the fluid was pressed (patents WO2004080367 , GB2434902) . The main disadvantage of these methods is their inability to deal with the fact that depending on the duration and intensity of pressure applied to the flask, and the volume of liquid inside said flask, the number of released drops may vary.

This limitation turns them into simple "event counters" where said event is when the fluid container is squeezed, with the ability to store the date and time of those events, but without being able to objectively correlate those events with released fluid drops.

These "pressure controllers" approaches were partially enhanced with patent US5152424, where a

- A -

transducer is used to detect the separation of drops from a fluid supply bottle.

However, none of these systems allow the assessment of the success of the fluid application to the target .

SUMMARY OF THE INVENTION

This invention refers to a process for monitoring the success of a fluid instillation to a non-static biological target, and a system to allow the execution of such process, with additional features that aid system users to self-instill mentioned fluid.

This system is composed of a device comprising means to contain a fluid dispensing container as for example a drop-dispenser, a video-camera and physical memory able to store videos depicting fluid drops trajectory when instilled, from the instant they leave the said fluid dispensing container until they reach the non- static biological target.

The device also contains an inclination sensor that combined with a microcontroller informs the device's user regarding the optimal angle of inclination to correctly instill said fluid to the target.

The videos acquired during the fluid instillation are then processed with signal and image processing algorithms to identify image regions corresponding to target visual characteristics and fluid location at each instant, which for example in the specific case of the non- static biological target being an eye, said characteristics can be the iris region and palpebrae position.

Data gathered by the device is sent to a remote computational platform which contains software that enables a third user in charge of evaluating the success of the fluid administration, for example a researcher or a physician, to review and analyze the recorded events and processed data.

BRIEF DESCRIPTION OF THE DRAWINGS

The following descriptions are based on the attached drawings in which, without any limitative intention, are graphically represented structures and concepts .

- Figure 1, a comprehensive view of the device with target support structure attached;

- Figure 2, front, top, and side sectional views of the structure which allows the definition of the adequate position between the target and the device

- Figure 3, device's side sectional view;

- Figure 4, device's top view;

- Figure 5, device's rear view;

- Figure 6, device's side view;

- Figure 7, representation of the block diagram for the device 1;

- Figure 8, frontal perspective view of device's possible alternative configuration;

- Figure 9, lateral perspective view of device's possible alternative configuration;

- Figure 10, device alignment problem illustration;

- Figure 11, block diagram illustration of the sequence of steps required to configure the system;

DETAILED DESCRIPTION OF THE INVENTION

For illustrative purposes, and without any limitative character, the present invention will be described in detail by referring to the attached figures. This invention is not by any means limited in its application to the construction details and component organization herein mentioned or illustrated. This invention might exist in other models of embodiment and might be created and implemented in alternative configurations, since various modifications may be made by a person of ordinary skill in the art. Likewise, use of syntax and technical wording should not be interpreted as limitative. The use of "included", "containing", "existing", "composed", "involving", and variations of these are made to include the above mentioned and their equivalent .

The present invention addresses a process to monitor the success of the administration of a fluid to a target dispensed by a fluid dispensing container 33 inserted in device 1, involving some or all of the following steps:

a) Device 1 inclination detection; b) Alarm emission when device 1 inclination is within a predetermined programmable interval;

- S -

c) Detection of fluid administration attempt, for example by monitoring pressure rise within the fluid dispensing container 33; d) Assessment of the simultaneous occurrence of inclination alarm event b) and fluid administration attempt event c) ; e) Synchronize the image acquisition beginning with the occurrence described in d) ; f) Electronic capture of a plurality of images regarding the action of fluid administration, where images represent distinct and sequential instants; g) Analysis of gathered data to determine target state; h) Analysis of gathered data to identify target; i) Analysis of gathered data to determine the fluid location in each instant; j) Evaluation of the analysis from g) , h) and i) to determine the overall success of fluid administration; k) The results are displayed;

In order to perform the abovementioned steps, the use of a system to gather data regarding fluid administration to the target is required. This system is composed by two main elements: a portable device 1, and a computational platform 40, from now on referred to as 'Computer' , without excluding other computational means suitable to the intended purpose, equipped with specific software and peripherals.

Said device 1 that is part of the described system contains :

a) Means 32 to contain a fluid dispensing container 33; b) Element 2 for fixing the relative position between the portable device 1 and the target; c) Means 6 to acquire images; d) Means 9 to permanently store digital such as a nonvolatile memory; e) Means 8 to compress data gathered by the image acquisition means 6 mentioned in c) ; f) Means 15 to assess portable device 1 inclination; g) Means 14 to measure time; h) Means to allow the physical coupling of element described in b) to said portable device 1; i) Alarm emission means 18 and 20, whereas said alarms will occur under predetermined programmable conditions, preferably on certain dates and hours, when the device is within certain inclination intervals, and when the energy level in energy storage means 13 is under a predetermined value; j) Means 17 to communicate data with remote systems; k) Means 13 to store electrical energy;

In order to clarify the human intervention on the system workflow, there will be defined two distinct users with different roles. The person that will use the portable device 1 to administer fluids to the target will from now on be mentioned just as 'User' , and the person that will

evaluate the success of such administration will be referred as Evaluator.

As seen in figure 1, portable device 1 is composed of a hollow structure, preferably made of a rigid material such as plastic or metal, able to contain a plurality of mechanical and electronic components within its interior cavity 37 - visible in figure 3 -, for example Printed Circuit Boards (PCBs) , where only for image simplification purposes, said PCBs are not shown, and said PCBs contain a plurality of circuits, sensors, and other electronic components that will be described in detail later in this document. The abovementioned rigid hollow structure will also be equipped with means to contain a fluid dispensing container 33, where said means exist as a cavity 32 within the portable device 1 structure.

Portable device 1 also contains means to attach rigid element 2, whose role is to fix the relative position between portable device 1 and the desired target, and is shown in detail in figure 2, where the abovementioned means for attachment consist in two cavities, preferably located at the top of the portable device 1, as visible in figures 1 , 4 and 5.

Figure 2 illustrates the preferable configuration for element 2. In it, the attachment rods 24 slide into cavities 23 of device 1, being the distance between the fluid dispensing container tip and the target partially

defined by the length of poles 25, to which is added the height of target contact element 26. This target contact element 26 is physically shaped to stably touch the target, for example, in the specific case of target being an eye, said element 26 will preferably be oval shaped as shown in Figure 2. Additionally, the region of element 26 that touches the target is preferably shaped in a way that does not cause damage or induce discomfort upon contact with the target or its surroundings.

As for the support structure 2, the length of poles 25 must be designed accordingly to the image acquisition means 6 and lens 3 focal distance, and accordingly with angles between said poles 25 and both ring 26 and fixation rods 24, that might be different from the ones depicted as an example in several images, as long as the center point of ring 26 is collinear with the camera's optical axis in such way that the area defined by the ring is being imaged by image acquisition means.

It will herein be defined the expression "optimal angle of use" , which refers to the device 1 inclination whenever the imaginary line that exists between the center of ring 26 and the extremity 4 of the fluid dispensing container 33 through which the fluid is dispensed, is aligned with ^' the imaginary line connecting one to the center of earth, in such way that any fluid stream released will free fall to the center of ring 26.

Figure 3 illustrates without limitation, a device 1 cross-section where image acquisition means 6 and optical means 3 for focus correction are visible, these being preferably in a fixed position, preferably connected to device casing, in such way that their optical axis is centered with the target expected position.

Figure 3 also depicts the positioning of aperture 31, which will be crossed by flange 28 of lever 27, being this aperture positioned in such way that when a fluid dispensing container is correctly placed within the device

1 casing, flange 28 slides through said aperture 31 and compresses the lateral wall of the fluid dispensing container 33. Visible cavity 32 will also contain a fluid dispensing container 33, whereas the dimension of said cavity 32 and said container 33 will define the position of extremity 4, where preferably the extremity 4 is partially within the scene captured by the image acquisition means, without obstructing the target.

Figure 6 depicts the device's frontal view, in which one can see the preferred position, shape, and dimension of buttons 10 and 11, apertures set 35 which are related to means 18 and 19 for luminous alarms, and apertures set 36 related to means 20 for sonorous alarms.

It is also depicted axis 29 of lever 27, where said axis allows connection from the abovementioned lever

27 to device 1 through hinge 30 for mechanical coupling.

Figure 7 depicts a conceptual representation of the functional elements that compose the device's architecture. Said elements include but are not limited to, means to acquire images 6, preferably a CCD or CMOS camera, with such temporal and spatial acquisition resolution that acquired images allow the execution of the process for the success assessment, for example a minimum spatial resolution of 640 pixel columns by 480 pixel lines, and a minimum temporal resolution of preferably 30 frames per second.

Images gathered by image acquisition means 6 are stored with reference to the time they were acquired in a non volatile memory, being this process controlled by a controller circuit 12, composed for example by one or more micro-controllers. Illumination means 5 that illuminate target and surroundings can be for example a Light Emitting Diode (LED) , and preferably said illumination means 5 activation is synchronized with the image acquisition means 6 in such way that is illuminating the scene only when the image acquisition means 6 are recording images.

Data originated in the image acquisition means 6 can be sent to a volatile memory 7, being compressed by a data-compressor 8, for example one working in real-time, being the data-transmission process between image acquisition means 6, volatile memory 7, and data-compressor 8 controlled by the controller 12.

Preferably, cavity 32 is shaped in a way that enables the position of fluid dispensing extremity 4 of fluid dispensing container 33 to be shown in the sequences of images acquired by image acquisition means.

In order to provide feedback to the User, the device can contain sound emitters 20, for example a speaker, and luminous indicators 18 and 19, for example colored LEDs . In order to interact with the User and receive inputs, device 1 contains means 10 and 11 to receive said inputs, being these means 10 and 11 for example buttons .

Button functions are programmable, for example button 11 can signal controller 12 to alternate between ON and OFF state, where when in the ON state all circuits and components are active, controller 12 actively evaluates device 1 inclination, alarms are emitted by alarm emission means 18 or 20 when the distance between device 1 inclination and "optimal angle of usage" is within certain programmable intervals. When it is in the OFF state, only the components required to evaluate current time and compare it to defined alarm conditions are active, thus being inactive the remaining components not necessary for said time control and comparison task inactive, where said remaining components are for example image acquisition means 6, inclination sensor 15.

When the device is in the ON state, upon lever 27 pressure while a fluid dispensing container 33 is within correspondent cavity 32, flange 28 will act upon said fluid dispensing container 33 in such way that will cause the fluid to be dispensed. Said dispensing action is detected by an appropriated sensor, controlling for example pressure between fluid dispensing container 33 and flange 28, in which case said sensor can, for example, be a piezzo- electric crystal .

In order to perform device 1 inclination assessment mentioned in this document, device 1 is equipped with means 15 to perform such a task, where said means are composed for example by a three axis accelerometer .

Other device 1 element is means 14 to control time, being said time-controlling means 14 composed for example by a quartz crystal clock, that when associated with controller 12 allows it to permanently monitor date and time.

Alarms will be emitted in certain pre-determined instants, being said alarms preferably managed by Controller 12, and being said instants preferably defined by programmable information stored in non-volatile memory 9, and being said alarm emission emitted by alarm emission means 18 or 20, being possible to temporary silence said alarms by using User input means 10, and permanently by performing a fluid administration.

Controller 12 will use clock 14 information whenever data from image acquisition means 6 is stored in non-volatile memory 9, in order assign a timestamp to acquired images or sequence of images .

While device is in the ON mode, when an administration attempt is detected by sensor 16, means for image acquisition 6 will become active and start recording. This recording state can end upon a set of programmable events, for example after a certain programmable amount of time, for example 8 seconds or when device inclination leaves a certain programmable interval .

All the elements present in device 1 are powered by means 13 to store an electrical charge, for example a rechargeable battery, which may be charged through an electrical connector 21.

Device 1 contains circuit 22 to analyze the amount of electrical charge present in the battery, being said amount communicated to controller 12, which evaluates the mentioned charge amount and triggers a programmed event upon certain conditions, for example when charge amount is below 10% of its maximum capacity. Events triggered at said conditions can be for example luminous alarm 19, either by being permanently on or blinking, or a sonorous alarm 20, using for example intermittent audible tunes, being the

frequency of said intermittent alarms programmable, for example once every 20 minutes.

Device 1 contains means 17 to transfer data between non volatile memory 17 and a remote Computer 40, whereas this transference can be wire-based, for example USB, or wireless, for example UMTS.

Figure 8 depicts an alternative embodiment for device 1, where the implementation of this uses the fact that many commercially available devices are already endowed with many of the elements that compose device 1, for example mobile phones that are equipped image acquisition cameras 6, illumination means 5 such as LEDs, volatile memory 7, non-volatile memory 9, data compressor 8 such as MP4 , programmable buttons 10 and 11 to gather User inputs, speaker 20, clock 14, 3 -axis accelerometer equivalent to inclination sensor 15, battery 13, battery charge assessment circuit 22, means to provide visual feedback to the User equivalent to means 18 and 19, electrical connector 21, Bluetooth or GSM/UMTS equivalent to means to transmit data equivalent 17, and equivalent programmable microcontroller 12.

In this configuration, missing elements are mostly mechanical, and accordingly to exemplificative illustrations provided in Figure 8 and Figure 9, it is demonstrated that it is possible to implement the device described as a part of this invention by mechanically

coupling specific elements to an existing electronic device, for example a mobile phone.

This specific mobile phone configuration may include a software component to allow the system to retain its functionalities, whereas said software would control visual and sonorous feedback, handle User inputs through buttons, assess device inclination by using either a cellphone built-in inclination sensor or communicating with one embodied in the external mechanical structure, emitting alarms when said device in certain programmable inclination intervals, activating the camera recording function when certain programmable event occurs, where said recording records a sequence of images, and finishes when predetermined programmable conditions are met.

In either configuration, once said recording is finished, recorded data is stored in a non-volatile memory, for example in a video file format. Said file and associated data are automatically processed with algorithms to assess fluid administration success. Said file and associated data are sent to a remote Computer 40. Said file and associated data become available for review by the Evaluator in Computer 40 through the use of software for that purpose.

Figure 10 illustrates device 1 which is part of the system disclosed within this invention, and some of the possible variations of these in what concerns the relative

angles between camera optical axis 38, fluid predicted trajectory 39, and the remaining components which define the structure of element 2. Figure 10 is an illustrative example without limitation of the specific case where the target is an eye.

The system's main feature is the existence of an image acquisition means 6, whose optical axis 38 is aimed to a structure intended to surround the administration target, being this alignment either direct or indirect, for example through the use of mirrors. Additionally, if said fluid administration results in said fluids moving only under the action of gravity, gravity axis 39 that defines the path from said fluid since it leaves the extremity 4 of fluid dispensing container 33 intersects or nearly intersects the optical axis of the abovementioned image acquisition means in such way that the whole target is imaged by said image acquisition means 6.

Figure 10 illustrates, providing a non limitative example the specific case whereas the target is an eye, slight variations that might occur in the embodiment of the device and that might influence the device's intended angle of usage, being said variations visible for example in the relative angles within structure 2, and between said structure, device 1, image acquisition means 6 and associated optical axis 38, and fluid expected trajectory 39. Said variations will influence the definition of the "optimal angle of use", therefore influencing the alarm

conditions, and also influencing the device usage by the User, for example regarding the inclination head.

The system herein described contains the adequate hardware and software required to perform image processing tasks, where said image processing addresses the identification of the target, for example, when the target is an eye, said identification might address features present within iris patterns.

Image processing also addresses the evaluation of administration success by detecting fluid regions, and also target characteristics that can change along time and influence administration success, for example, in the specific case of ophthalmology, palpebrae position. By analyzing the progression of the fluid position and said target's variable characteristics it is possible to identify the conditions upon which said fluid reached said target, thus allowing to perform said administration success assessment .

The abovementioned adequate hardware and software that enables the execution of image processing tasks may be for example either present within device 1 or within Computer 40 to be used by the Evaluator.

The execution of the described process will preferably start by the usage of the described system, by

configuring device l's configurable parameters, being this configuration preferably performed by the Evaluator.

An example of the configuration process is depicted in Figure 11. The Evaluator may start system configuration by activating the abovementioned Computer 40 and device 1, and the associated software present in said Computer. In said software, the Evaluator selects a previously registered or imported User, or creates a new registration in case the User is not yet registered, by registering relevant data, as for example name, date of birth and therapy regimen schedule, and by capturing the target images necessary for the comparison process h) .

After the fluid administration attempt, gathered sequence of images documenting the fluid administration is transmitted to a remote platform with computing capabilities 40, by means 17 to transmit data between said device and said Computer 40. In the herein described process, there is no limitation to where the gathered data is analyzed, and therefore if said data analysis occurs within the device 1, results obtained are also transmitted from the device to the Computer 40.

All gathered and processed data, which includes for example videos with associated date and time in which said videos were acquired are stored within said Computer 40, where they become available to be accessed and reviewed by the Evaluator through a software developed for that specific purpose. Although not illustrated, visualization

interface can for example depict the regular format for date-time calendars, depicting different hours in each line and different days in each column, and represent each administration with an icon in said calendar, whereas said icon features such as for example shape and color represent distinct results derived from data analysis, for example associating green icons with success and red icons with failure .

SYSTEM ELEMENTS LIST

Element 1 - Device;

Element 2 - Structure to define the relative position between the target expected position and the device;

Element 3 - Optical Lens;

Element 4 - Fluid dispensing container dispensing aperture;

Element 5 - Illumination means, for example LED;

Element 6 - Camera;

Element 7 - Volatile Memory;

Element 8 - Data compressor;

Element 9 - Non volatile memory;

Element 10 - Button 1;

Element 11 - Button 2;

Element 12 - Microcontroller;

Element 13 - Battery;

Element 14 - Clock;

Element 15 - Inclination sensor;

Element 16 - Sensor for detection of fluid administration attempts ;

Element 17 - Data Transmission Module;

Element 18 - Luminous alarm 1;

Element 19 - Luminous alarm 2;

Element 20 - Speaker;

Element 21 - Electrical Connector;

Element 22 - Battery charge assessment circuit;

Element 23 - Cavities;

Element 24 - Fixation rods;

Element 25 - Poles;

Element 26 - Target contact structure;

Element 27 - Lever;

Element 28 - Lever Flange;

Element 29 - Lever axis;

Element 30 - Hinge;

Element 31 - Aperture;

Element 32 - Cavity for fluid dispensing;

Element 33 - Fluid dispensing container;

Element 34 - Structure attachable to an existing third device;

Element 35 - Translucent LED windows;

Element 36 - Speaker holes;

Element 37 - Device interior cavity;

Element 38 - Camera optical axis;

Element 39 - Fluid predicted movement axis;

Element 40 - Remote computational system;