Patent Application
20230293018
The present invention relates generally to blood sampling devices and methods, and more specifically to methods and apparatus for blood analysis and blood monitoring.
Internal bleeding is a large cause of death. Failure to detect blood loss in real-time is a leading cause for medically preventable death. Fast diagnosis and control of bleeding is critical for the prevention of irreversible cell changes and severe damage to vital organs during hypovolemic shock. Evaluation of the actual blood loss and diagnosis of the hemodynamic status is a great challenge for medical staff. This is even a greater challenge in accidents, sports injuries or in military combat.
More than 25% of the injuries during battle include hemorrhage, while 10% of them include internal bleeding requiring immediate evacuation. It is extremely hard to diagnose blood loss before 30% of blood volume is lost, leading to changes in pulse, blood pressure and consciousness.
The monitoring of hemoglobin (Hgb) levels and pulse can provide an alert regarding blood loss and identify cases of undiagnosed or underestimated internal bleeding. Recent studies show that following massive bleeding changes in Hgb levels can be noticed in the measured blood within less than half an hour of the incident, due to rapid fluid shift to the inner vascular space. This contrasts with trauma and surgeon paradigm.
Many trauma patients suffer from internal bleeding, due to falls, vehicle accidents, gunshot wounds and other types of traumas. Many trauma patients die or become unconscious due to internal bleeding. Internal bleeding is one of the most serious consequences of trauma. Usually, the bleeding results from obvious injuries that require rapid medical attention. Internal bleeding may also occur after a less severe trauma or be delayed by hours or days.
Internal bleeding may also occur in other cases such as surgeries or complicated labors.
In many cases, the internal bleeding results from non-obvious internal injuries. These can be lethal, if not detected and treated.
To date, there are very few reliable methods, if any, for real-time diagnosis of internal bleeding in a patient. Thus, all too often, by the time the patient is diagnosed as suffering from internal bleeding, significant damage can be induced to the brain or other organs, or the patient may be dead.
There, thus remains an urgent need to develop improved methods and apparatus for detecting internal bleeding in a human subject.
There remains an urgent need for improved methods and apparatus for detecting and quantifying blood loss in mammalian subjects.
It is an object of some aspects of the present invention is to provide improved methods, devices and systems for a monitoring blood level over extended periods of time in a mammalian subject.
It is another object of some aspects of the present invention is to provide improved methods and systems for detecting internal bleeding in a mammalian subject.
In some embodiments of the present invention, improved methods and apparatus are provided for drawing blood over many hours from a human subject.
In some embodiments of the present invention, improved methods and apparatus and devices are provided for optical analysis of whole blood from a mammalian subject.
In some further embodiments of the present invention, improved methods and apparatus and devices are provided for continuous or semi-continuous optical analysis of whole blood from a mammalian subject over many hours.
In some embodiments of the present invention, improved methods and apparatus are provided for detecting real-time internal bleeding in a human subject.
In other embodiments of the present invention, a method and system is described for providing continuous or semi-continuous monitoring of a human subject to detect internal bleeding or other whole blood indices. The invention further comprises systems, methods and devices for controlled monitoring, personalized monitoring and remote monitoring of blood parameters.
In additional embodiments of the present invention, a system is provided for detecting blood loss in a mammalian subject, the system including some or all of:
In further embodiments of the present invention, the processor is further adapted to provide an alarm if the subject is suffering from at least one of blood loss and internal bleeding or any other blood indicator alarm it was programmed to test and alert for.
In further embodiments of the present invention, the invention provides systems and methods for early detection of body malfunctions in a patient based on real time monitoring of blood parameters from a catheterized patent, indicative of changes of state in the human body.
More particularly, the present invention relates to a diagnostic method, system and apparatus for rapidly detecting, at least one change in a trend of a blood parameter indicative of a body malfunction.
Yet more particularly, the present invention relates to a diagnostic method, system and apparatus for real-time detection of at least one change in a trend of a blood parameter indicative of a body malfunction.
Additionally, the present invention relates to a diagnostic method, system and apparatus for real-time detection of internal bleeding, detected by at least one change in a trend of a blood parameter.
According to some embodiments of the present invention, the blood parameter includes a hemoglobin level.—in other cases may be glucose, natrium, sodium bicarbonate, creatinine, oxygen saturation, blood pH. lactate etc.
Additionally, the present invention provides a system for the automatic and continuous monitoring of hemoglobin and pulse from a patient—absolute values and changes.
The invention will now be described in connection with certain preferred embodiments with reference to the following illustrative figures so that it may be more fully understood.
With specific reference now to the figures in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.
In the drawings:
In all the figures similar reference numerals identify similar parts.
In the detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that these are specific embodiments and that the present invention may be practiced also in different ways that embody the characterizing features of the invention as described and claimed herein.
Reference is now made to
According to some embodiments, the present invention includes an analytical disposable miniature device, assembled on a Venflon (or intravenous cannula) communicating with a remote computerized station. The device automatically and frequently draws a minimal amount of blood (few hundreds microliters) for measuring hemoglobin (Hgb) levels. Hemo-dilution is considered for Hgb correction, as may be needed, using an algorithm (as described herein—see
Additionally, pulse is measured as a complementary index using a pulse meter (not shown) attached to the device. The device is configured to detect and/or diagnose dangerous health situations in a patient/subject. This is performed by integrating between the pulse and Hgb changes, monitored over time. According to additional embodiments, changes in a patient's bodily function can be detected/diagnosed using Hgb monitoring alone. The device may be used as a platform for additional sensors for blood monitoring, such as oxygen, lactate, glucose, creatinine, blood pH and electrolytes blood level. The device may also be a part of fluid balance follow up.
The device is constructed and configured to be easily portable, inexpensive and consumes low power, due to its small size and its utility on basic modern technologies. The device is further constructed and configured to be durable in field conditions and simple to operate for easy accessibility. The measured Hgb and pulse data is sent at an adjusted frequency by Bluetooth (or other transmission method) to a main medical station (not shown) allowing the indices to be monitored and analyzed locally and/or remotely.
The present invention system and devices are constructed and configured to optimize real-time evaluation of a patient's condition. This allows for urgent evaluation followed by improved medical treatment.
According to one embodiment as shown in
The device in
The device shown in the figures (
The device includes an electrical stopcock 214 which switches between three states: infusion constant dripping to the body through the infusion port 109 connected to an infusion reservoir 239, rinsing the device using the infusion liquid and pumping blood from the body into the device through 202.
The frequency at which the patient's blood is sampled, is controlled by an automated switch, configured to turn the device battery on and off. More information regarding the electrical system can be found in
In one embodiment, algorithms include:
In one embodiment the device is a one-use and/or disposable measurement device which is “patched to the patient”, vis-a-vis the current methods of separated measurement devices of blood samples which located at the POC (“Point of Care” i.e. patient's bed or mobile carriage).
In one embodiment, the measurement device is configured to obtain measurements in a continuous manner. In another embodiment, measurements are performed automatically every several minutes by blood is being vacuumed/pulled/extracted from the subject/patient and screened within the closed device. This is performed vis-à-vis current methods of taking a blood sample from a patient/subject and transferring/moving the sample to a separated detached measurement device.
In one embodiment the device is connected to an artery and the blood is drawn into the device due to pressure differences between the device and blood vessel or the blood is controllably pumped by a pump.
In one embodiment, the system is built from a disposable and portable device and a stationary unit (any computer or phone with a designated program). The disposable unit will be assembled on a Venflon.
The blood sample is illuminated by the LED and the photodiode detects the intensity of light which passes the cuvette. The data is converted into Hgb concentration and is presented on the device screen. Then the cuvette is discarded. Some examples are shown in
One non-limiting example of cuvette is shown in
A schematic diagram of the electrical elements, included in the portable unit of the device, is presented in
The setup of the electrical elements should not be deemed limiting. Many variations are possible. The device also may include a battery sampler 334, another optional BT 344, a current and voltage sampling element 348, one or more connectors 336, a pump motor 350, all in electrical connection with a power supply 356. A driver and encoder 342 may be used to control the infusion.
According to some embodiments, the present invention includes an analytical disposable miniature device assembled on a Venflon communicating with a remote computerized station. The device is constructed and configured to automatically and frequently draw a minimal amount of blood for measuring Hgb levels. Hemo-dilution will be considered for Hgb correction as needed. Additionally, pulse is measured as a complementary index using a pulse meter attached to the device. The device system will be able to diagnose health danger situations with high accuracy by measuring Hgb levels and changes monitored with time. The device is a platform for additional sensors for blood monitoring such as, but not limited to, oxygen, lactate, glucose and electrolytes blood level, natrium, sodium, bicarbonate, creatinine, oxygen saturation, blood PH, natrium, sodium, bicarbonate, creatinine, oxygen saturation, blood pH,
The device is aimed to be easily portable, cheap and will consume low power due to its small size and its utility on basic modern technologies. The device is planned to be durable at field conditions and easy to operate for easy accessibility. The measured Hgb data will be sent at an adjusted frequency by Bluetooth (or other communication method) to the main medical station allowing the indices to be monitored and analyzed. The methods of the present invention are directed to optimize evaluation of a patient's condition in real-time, thereby allowing urgency evaluation, followed by a better and more rapid medical treatment.
Reference is now made to
The system is connected to the Venflon 400—with the strips/straps (optional) There may be another method for attaching the device to the patient. Initially, the device is switched ON in a switching on step 401. Then in a calibration step 402, a person using the device check reference values and calibrates the device. The device starts to work and automatically performs an Initializtion Built In Test (IBIT) process and calibration in a self-calibration step 403. The device draws a small amount of blood from the patient and in sampling steps 406, 413. Thereafter, in an activate algorithm step 412 and verifying step 411, the device is operative to start sampling through algorithm process.
If the sensor value is OK but outside the safe values of Hb levels for example, emergency procedure should take place (for example: buzz alert). The system continues to the cleaning stage to avoid blood coagulation in the sampling cell and total system in a cleaning device step 410.
After saline+heparin cleaning, the sensor checks if the sampling cell is clean by radiating it and checking if the signal reaches the voltage zero point in a sensor testing step 409. If cell is not clean, another cleaning procedure takes place in an infusion step 410. If thereafter, the cell is found to be clean, valve 202 (
The first step is initializing the sensor by start command in a start step 1002. Then the photodetector (PD) setpoint is being determined according to blood reception at the specific wavelength in a photodetector set point step 1004. This is followed by determining the right LED step according to the accuracy and time required, in a LED determining step 1006. Then the LED receives a command to turn ON the device in an LED activation step 1008. It then performs a measurement in a blood sample measuring step 1010. Then, it asks whether it is measuring blood or rinsing liquid in a checking liquid composition step 1014. There is a different initial testing point for each procedure (a defining initial testing point for cleaning step 1012/or define initial testing point for a blood procedure step 1016. After blood sampling or rinsing, the LED intensity of the radiation is changed in defined steps until the PD reaches its initially determined setpoint value. In the beginning, the LED steps change with a low resolution in a low resolution step 1018. If the PD level reaches its setpoint in a showing value step 1026, it means that X tests have been performed and sufficient resolution achieved. If not, decrease LED resolution 1028 and search again for PD setpoint 1018.
Thereafter, then the LED value is set in a setting step and sent to output steps (PD higher or lower than set point checking step 1022. If LED has not found a value which correlates to a PD setpoint value in an LED increasing step 1030 then its step size is lowered in one step (step 1032) or increased (step 1030) in accordance with the distance from a PD setpoint.
Turning to
The ability of the system to remain optically clean after several blood draws along a four-hour experiment is presented in
Reference is now made to
Fresh whole blood samples were drawn from female patients into test tubes and inserted into the cuvette by a syringe within 24 hours. Then the blood was illuminated by the LED and analyzed after the photodetector sensing. The test tubes were cooled to approximately 4° C. during the time gap between blood drawing and testing. Each blood sample was drawn twice so one tube was tested for Hb using standard laboratory test and the other by the current innovation. The setup of the current innovation was rinsed using saline and heparin after each test.
The parameters affecting the results include optical pathlength, cuvette optical transparency, light ray diameter and intensity, photodiode set-point and sensitivity, and stray light. Stray light is a function of air bubbles, red blood cells scattering, and cuvette boundaries. Light scattering is assumed to be the main reason for deviation from linearity at higher Hgb levels.
While the experiment conducted using a system connected to a rabbit's blood stream showed good linearity between detector output voltage and Hb levels, the results achieved for humans showed some discrepancy from linearity especially for Hb range of 10-13 gr/dL. The experimental setups of the later are more susceptible to light scattering and errors as it is remote from the body and less consistent. For example, there were air bubbles involved in these experiments and the cuvette was made of polished polycarbonate instead of quartz (less optically clear).
1. Algorithm for Timing Blood Draw Intervals
Characteristics of the Devices of the Present Invention
They are wearable, cheap, disposable, accurate, automatic, remote monitoring and alerts devices. The devices of the present invention are constructed and configured to enable a diagnostic method for detecting at least one change in a trend of a blood parameter indicative of a body malfunction, the method comprising continuously or semi-continuously monitoring at least one blood parameter selected from at least one of: a hemoglobin level, an albumin level, an oxygen level, a sodium level, a potassium level, a lactate level and pH and combinations thereof of a catheterized patient; whereby at least one dynamic trend is monitored so as to detect one or more changes in said at least one dynamic trend to indicate said body malfunction in said patient.
Electrical Stopcock
In order to allow infusion transmission through the same Venflon as the device a unique stopcock is designed. The stopcock has three ports—one goes into the venflon, second to the device and third connected to the infusion.
Algorithms
2. Algorithm for Diagnosing Internal Bleeding and Alerting
3. Algorithm Process for Diagnosing Internal Bleeding Using Hgb Levels Analysis Under Hemodilution
Detailed Description of Device Components (without Limitations):
The device uses an optical sensor for transmitting radiation known to be absorbed by Hgb. The radiation is detected by a detector, photodiode.
Blood for testing is drawn from the blood flow into a reservoir using a type pump. The data from the device is transmitted to the “display” via Blue Tooth or other communication methods. The device will be power ON by switch embedded in the device.
The frequency in which the blood is being tested is controlled by an automated switch turning the device battery on and off.
The device is stationed stably and tightly on the arm using strips and will allow a flexible assembly on the Venflon.
Optical sensor system: The sensor is based on a photodiode with high sensitivity and a constant working point. The transducer is a LED with more than 1 WATT working in constant voltage. Since the blood sample varies from being dilute to thick liquid, the electrical current of the transducer is increased until the sensor reaches its working point by attenuator current control. This method allows avoiding saturation.
The LED is monochromatic and transmits wavelength at approximately 550 nm which is Hgb isosbestic point. At this point oxyhemoglobin, hemoglobin and carboxyhemoglobin have the same absorption coefficient and allow improved accuracy of the measurements (3% error) with minimal number of wavelengths used to test Hgb concentration. The absorption of light transmitted through the blood sample is correlated to the concentration of Hgb levels in the blood. Using a calibrated plot the Hgb levels can be extracted from the measurements and monitored over time.
The wavelength(s) used depends upon the parameter to be detected. One non-limiting example is that of hemoglobin, wherein hemoglobin is detected at around 550 nm, and wherein the at least one LED outputs radiation at around 550 nm. This wavelength is found to match the Isosbestic point of hemo, oxy and carboxyhemoglobin with identical absorption coefficient (extinction coefficient).
Since we only need the sum of the Hb derivatives, we can radiate the blood at the isobestic point only. Other forms of hemoglobin derivatives are assumed to be less than 3% of the Total hemoglobin concentration in most cases. If better accuracy is needed, more LEDS with additional wavelengths may be used.
Blood Pump:
The blood is drawn from the body using a pump in intervals.
Cuvette:
According to some embodiments, the cuvette is a flow through cell consisting of the blood sample allowing the blood to go through it from the Venflon to the waste. The cuvette is made from a transparent material in the visual range such as quartz, glass, plastics such as PMMA, polystyrene, polycarbonate, or other similar materials. The cuvette may be internally coated with an anti-coagulating coating such as heparin.
The cuvette is manufactured using injection molding or metalworking. The cuvette house is from a non-reflective and rigid material and prevents stray light from escaping or entering the cuvette. Typically, there is an approximately 1 mm diameter hole for light passage.
The optical path (cuvette thickness) ranges from 0.1-2 mm with two parallel faces. The cuvette shape should avoid blood clots and hemolysis. This is done by creating a continuous and constant passage of blood through the cuvette and minimal amount of unintentional chinks.
The cuvette dimensions (height and width) are large enough, so minimal amount of light is scattered in the boundaries later reaching the detector.
Outside this area the cuvette can be either transparent or opaque, as long as it blocks reflected radiation from entering the blood sample again. The cuvette withstands pressure of at least 1.5 bar.
Electrical Stopcock:
Electrical stopcock/4-way electrical valve: The system is mounted to a catheter (venflon) via stopcock (luer). The stopcock is connected to an infusion bag and to the cuvette. The stopcock allows regular body infusion irrigation. When a command from the artificial intelligent system is given (see algorithms), the valve stops the irrigation and allows the pump to draw blood through cuvette from the catheter. After wards, the valve allows flushing the whole device by infusion. After the system is flushed, the sensor checks that the cuvette is clean (signal—base line) and the valve is switched back to regular body irrigation. The infusion may include saline and heparin to lower the risk of blood coagulating in the system and in the catheter. The stopcock is also a check valve preventing the return of drawn blood to the body.
Attained results and analyses: The results and their analysis are attained on-line in less than 1 minute. For low Hgb levels, the alarm will immediately alert the staff. When there are normal Hgb levels but negative Hgb trend, the time it will take for the device to detect the bleeding depends on the rate at which the Hgb levels respond to the bleeding. For example, in acute bleeding situations, Hgb levels will change in less than 20 minutes and the device will alert accordingly. At lower bleeding rates, detection time might be longer.
The references cited herein teach many principles that are applicable to the present invention. Therefore the full contents of these publications are incorporated by reference herein where appropriate for teachings of additional or alternative details, features and/or technical background.
It is to be understood that the invention is not limited in its application to the details set forth in the description contained herein or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Those skilled in the art will readily appreciate that various modifications and changes can be applied to the embodiments of the invention as hereinbefore described without departing from its scope, defined in and by the appended claims.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/IL2021/050716 | 6/14/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63039758 | Jun 2020 | US |
