DESC:FIELD OF INVENTION
The present invention relates to a device for determination of component levels in fluids based on transmittance photometry using self-calibrated algorithm and a method for the same. Specifically, the invention relates to a smart compact and portable device and method to measure the total component level in fluids, that may be communicated over a wireless connection.

BACKGROUND
Devices meant for conducting photometric assays often function on the principle of transmittance photometry for measurement of fluid components, such as hemoglobin levels, blood sugar levels, urine HCG detection etc.

Anemia is the most serious complication of iron deficiency; it is also a significant cause of death. Therefore, hemoglobin is one of the most common blood components which requires testing in order to monitor the health status of a patient. Developing countries show a result of almost 50% of pregnant women with anemia. A variety of health issues including trauma care, blood donation, primary health care and epidemiological studies require accurate and user friendly blood testing devices as skilled persons to man laboratory devices for blood testing are limited and costly. Such limitations delay and obstruct timely testing and treatment of the patient.

The state-of-the-art methods for measuring total hemoglobin levels include the use of pathological blood analyzers, as disclosed in PCT International Publication No. WO 03/056327 A1, which relates to a method for quantitative hemoglobin determination in undiluted unhemolysed whole blood. Pathological blood analyzers require skilled persons to conduct the test, the devices are also cost inefficient and impractical for individuals to perform a quick, easy test with precision.

Conventional methods of measuring blood hemoglobin level require venous blood which is then diluted using different chemicals. Blood samples along with the reagents are added in the cuvette, these reagents lyse the blood cells then releasing hemoglobin hence making the sample stable for determining the hemoglobin level optically. But these kind of methods increase the cost of the process and making it less accessible to some parts of the world. Such is the case for Hemoglobin levels, Platelet count, WBC count, etc. and also for other fluid components such as urine testing for HCG content etc. So, there is a need for a method that will be cost effective whilst accurate for fluid component measurement.

For laboratory methods / techniques trained professionals are required for handling of body fluids, mixing with reagent and for operating complex machines. In laboratories there is no whole blood measurement performed where as there is always a need of dilution or mixing of reagent for measurement.

Machines claiming to measure component levels in unaltered body fluids follow two methods 1. Electrochemistry and 2. Transmittance/ reflectance photometry. Electrochemistry based machines may give inappropriate results whereas in case of transmittance or reflectance photometry based machines the cost involved for consumables is high.

Most fluid assay devices available in the market use expensive cuvettes which considerably increases the cost of the entire device. Unfortunately, cuvettes available in the market do not ensure uniform distribution of blood, simplified sampling processes, fixed volumes collected by capillary action of cuvette and often permit bubbles in the blood sample, each of these shortcomings considerably interfere in the fluid component measurements. Multiple efforts have been made in the industry to overcome at least one of these shortcomings. Such as by adding reagents to the cuvette walls. However, none of the attempts have concluded in a successful result while controlling the costs effectively. In fact, most attempts have concluded in increasing the costs of the basic cuvettes available in the market. Moreover, Cuvettes currently available require much larger and bulkier devices to conduct assays.

There is a lack of fluid component measuring systems designed for individual users, such that the system allows accurate readings with minimal user interference, allowing even an untrained individual to accurately measure hemoglobin in a simple manner.

Therefore, there is a need for a smart device to measure fluid components, which is cost effective, easy, quick, simple, user friendly and precise. Moreover, there is a need to overcome at least one of the abovementioned shortcomings.

OBJECT OF INVENTION
It has already been proposed that there is a need for a device which is simple, user friendly, compact and portable, to measure component level in fluids based on transmittance photometry.

The principal object of the present invention is to provide for a compact and portable device to quantifiably measure components in various fluids without the need of trained professionals to operate the device

Another object of the present invention is the to provide for a device for quick and accurate results by simplifying handling of blood and other body fluids using proprietary cuvette (Strivettes)

Another object of the present invention is to provide for a device which runs on algorithm based on transmittance photometry where absorbance by blood and other fluids is correlated with actual blood/fluid component

Another object of the present invention is to provide for a device which enables easy measurement of components in arterial and / or venous whole blood, urine, or such other fluids

Another object of the present invention is to provide a smart compact fluid component measuring system which can communicate over Bluetooth for data logging and analysis on later part.

Another object of the present invention is to provide a smart compact fluid component measuring system which enables real time data logging on smart phone with customized Application.

Another object of the present invention is to provide a device including an algorithm which will efficiently incorporate deviation occurring due to scattering phenomenon in the transmittance photometry.

Yet another object of the present invention is to provide a method to quantifiably measure components in a fluid with accuracy at least equivalent to a laboratory assay.

Yet another object of the present invention is to provide a device and method that enable intensity of the light source to be adjusted based on the absorbance capacity of sample fluid, to achieve optimum accuracy of readings.

SUMMARY OF INVENTION
Accordingly, the invention provides a compact and portable device to measure the total component level in fluids based on transmittance photometry comprising:
At least a dual light source;
At least a photosensor;
A receiving tray including at least two placeholders;
At least a transparent control strip and a cuvette, both having flat configuration;
A pre-programed, self-calibrating algorithm uploaded into the device;
A display screen; and
Onboard interface(s), all connected to a portable user interface by means of a wireless communication

There is also provided a method to quantitatively measure the total component level in fluids comprising the following steps:

Device is turned on and receiving tray is pulled out to initiate calibration;
Placing an optically clear strip as control in one placeholder and a Strivette containing fluid to be tested in the other placeholder of the receiving tray;
Once calibrated, the receiving tray is closed and the sample is exposed to two LED wavelengths alternatively for a period of ~10ms each
The light absorbance by the fluid of the two wavelengths is measured by the photosensor according to a preprogrammed algorithm
The fluid component is calculated by the algorithm based on the output of the photosensors and the same is communicated to the user by means of a user interface

BRIEF DESCRIPTION OF DRAWINGS
This invention is illustrated in the accompanying drawings, throughout which like reference numbers indicate corresponding parts in the various figures

Figure 1 shows an expanded view of the device focusing on parts of the device
Figure 2 & Figure 3 Shows an external view of the device being connected to a user interface by means of a wireless connection and a USB respectively
Figure 4 Shows the top view focusing on the onboard interface and display screen

DETAILED DESCRIPTION
According to various embodiments of the present invention that are described below a compact and portable device to measure the total component level in a fluid is provided. The device of the present invention comprises of at least a Photosensor; a means for emitting at least two LEDs of different wavelengths, placed equidistant from the photosensor; two cuvette holders, one for strip simulator and another for strip/ cuvette; strip simulator; proprietary strip / cuvettes titled as Strivettes; an onboard controller (12) of Fig 1; a wireless connectivity and/ or USB connectivity Fig 3. or any other communication media for convenient data transfer; an interface for data storage and analysis

In one of the embodiments of the present invention the compact and portable device to measure the total component level in fluids comprises of:
At least dual light source (4) & (5) of Fig 1.;
At least a photosensor (1) of Fig 1.;
A receiving tray (9) of Fig 1 including at least two placeholders (7)& (10) of Fig 1.;
At least a transparent control strip (11) of Fig 1. and a cuvette (8) of Fig 1.,both having flat configuration and optical path length is more than 0.85mm;
A pre-programed, self-calibrating algorithm uploaded into the device chip/controller (12) of Fig1.;
A display screen (14) of Fig 1 & 4.; and
Onboard interface(s) (13) of Fig. 1 & 4, all connected to a portable user interface Fig 2. by means of a wireless communication Fig 3.
Wherein, the portable user interface may be selected from but not limited to a mobile phone, a tablet, a computer, inter alia and the wireless communication may be selected from but not limited to Bluetooth, WiFi connection, internet connection, or such other wireless communication.

In an embodiment of the present invention, the self-calibrating algorithm uploaded into the device is based on transmittance photometry where absorbance by fluid is correlated with actual fluid component

In an embodiment of the present invention the light source preferably comprises two LEDs (4) & (5) of Fig 1. Located on an LED board (6) of Fig 1 supported by an LED board holder (2) of Fig 1, having different wavelengths each emitted alternatively for a defined period of time i.e. ~10ms

In an embodiment of the present invention, the intensity of the light source may be adjusted based on the absorbance capacity of sample fluid.

In an embodiment of the present invention, the photosensor may be a photodiode or such other photosensor which senses light having a wavelength ranging from 400nm to 1100nm and is optically aligned with the light source, transparent control strip and cuvette.

In an embodiment of the present invention, the photosensor senses light having wavelength ranging from 500-600nm and 800-980nm as the first and second wavelengths respectively, for measuring contents of blood sample, preferably for Hemoglobin measurement & turbidity correction and wavelength ranging from 400-500nm and 550-650nm as the first and second wavelengths respectively, for measuring contents of a serum sample, preferably for bilirubin measurement & turbidity correction. Wherein the first wavelength measures the absorbance of the fluid component while the second wavelength measures the fluid turbidity.

The device of the present invention is capable of assaying fluids of various kinds. Therefore, the same device can be used for measuring hemoglobin content from whole blood or bilirubin content from serum.

For hemoglobin assay wavelength used is between 500 – 600 nm, green color LED. The absorption of this light passing through the cuvette containing blood is measured and it is derivate to give the exact hemoglobin value. Here wavelength 800 – 980 nm is used to counter/ adjust/ manipulate turbidity within the fluid / blood.

For bilirubin assay, wavelength used is between 400 – 500 nm, blue color LED. The absorption of this light passing through the cuvette containing serum is measured and it is derivate to give exact bilirubin values. Here wavelength 550 – 650nm is used to counter/ adjust/ manipulate turbidity within the fluid / serum.

In an embodiment of the present invention, the device is made of materials selected from but not limited to plastic, stainless steel, or a combination thereof and measures a maximum of 93mm x 141mm, the cuvette holder measures 30mm x 9mm having a maximum thickness 0.3mm more than the proprietary cuvette named Strivette.

The device of the present invention is capable of measuring component level in fluids including but not limited to whole blood, serum, urine, saliva, amongst other fluids by accommodating an appropriate wavelength and intensity of LED according to the selected sample to be measured

A further embodiment of the present invention, presents a method to quantitatively measure the total component level in fluids comprising:
Device is turned on and receiving tray is pulled out to initiate calibration;
Placing an optically clear strip as control in one placeholder and a Strivette containing fluid to be tested in the other place holder of the receiving tray;
Once calibrated, the receiving tray is closed and the sample is exposed to two LED wavelengths alternatively for a period of ~10ms each
The light absorbance by the fluid of the two wavelengths is measured by the photosensor according to a preprogrammed algorithm
The fluid component is calculated by the algorithm based on the output of the photosensors and the same is communicated to the user by means of a user interface

Wherein, the absorbance readings of the wavelength is detected by the photosensor and considered by the algorithm in calculating the true absorbance of the fluid after subtracting the fluid turbidity amongst other deviation/scattering components, to accurately quantify the fluid component value.

In an embodiment of the present invention, the distance between the LED source and the photosensor may be adjusted to achieve a lower path length.

The defined small size of cuvettes greatly contributes towards achieving a lower path length and ensuring a straight light path. This results in reduced travel time of light.

The device is also advantageous in that it uses lower intensities of the LED so that less power is consumed.

Various intensities of the same wavelength (500-550nm) can be used to achieve desired output levels. To achieve a dynamic range of a Hemoglobin measurement, either a single or multiple intensities may be used to obtain accurate readings. However, a single intensity may be accurate for a range of 5 to 15 g/dL of hemoglobin. Fora higher range of 0-15 to 15-25 g/dL of hemoglobin two intensities is preferred to obtain accurate readings.

The intensities may be increased from one to four based on the accuracy obtained, the accuracy is judged by overlapping between readings while using different intensities.

In one of the embodiments of the present invention the Photosensor used can sense light having wavelength ranging from 400nm to 1100nm. Wherein, the Photosensor receives the transmitted light after the absorption by the fluid in the Strivette. Based on the light received by the photosensor the response of photosensor changes which results in different set of outputs. The values obtained are from both the LEDs having different wavelengths, at different time instants. Based on the output of the photosensor and developed algorithm, fluid component values are determined. The device runs on algorithm based on transmittance photometry where absorbance by fluid is correlated with actual fluid component.

The scattering of light is not only due to the fluid components, there exist other scattering factors such as material used in construction of cuvettes, optical interference in the path of light and detector, temperature, component variation etc. Selection of Wavelengths is based on isosbestic point of absorption of the fluid components. Selected wavelengths are used in a series, in a gradually ascending manner to determine the levels of fluid components accurately and scattering is eliminated using these combinations despite of turbidity of fluid.
In one embodiment of the present invention the cuvette holder is designed specifically to accommodate proprietary strip / cuvettes titled as Strivettes which are smaller, more compact and enable accurate reading of the fluid sample. Therefore, allowing the entire device to reduce in size and making it compact and portable. Moreover, using a Strivette for a device of the present invention is important as it is important to have a pre-determined value of the thickness of the cuvette to be used. The pre-defined thickness defines the optical path length, based on which the LED will glow.

In one embodiment of the present invention, the algorithm is self-calibrated considering various components such as the pre-determined path length, temperature variation and component variation. Such component variation allows for relaxed component tolerance, this is crucial in reducing the cost of the device.

In one of the embodiments of the present invention, the proprietary Strivette comprises of two pre-treated optically clear sheets glued together using a middle layer of an adhesive sheet having uniform thickness. This uniform distance of the internal space between the two optically clear sheets generates a capillary action with a pre-defined optical path, the defined capillary structure also offers a pre-determined capillary volume, features that ensure uniform drawing of blood. The pre-treatment of optically clear sheets makes the sheets hydrophilic in nature increasing the affinity of the internal cuvette walls towards the fluid to be tested. Thereby enabling accurate drawing of blood without any intervention, as required for accurate fluid component measuring. The Strivettes are disposable, compact, sustain low fluid volumes and are made using a method that guarantees accuracy of drawing fluid void of air bubbles. The Strivettes enable testing arterial and / or venous whole blood, urine, or such other fluids without the need of any diluents or reagents or chemicals. This reduces the procedure involved in calculating the fluid component level as compared to the traditional methods. The lack of reagents and chemicals also provide for ease of storage and usage of Strivettes. Strivettes have a predefined fixed volume of ~ 1uL- ~20uL as required, the optical path length is morethan 0.85mm.

An embodiment of the present invention discloses a compact, portable device to measure total hemoglobin level using small blood volumes. The size of the device makes it portable and easier to handle. Wherein, the blood to be tested may be arterial and / or venous whole blood.

One aspect of the present invention discloses a method of quantitatively measuring fluid component level by the following steps:

System is turned on and tray of the system is pulled out. Every time the tray is pulled out, the system calibrates itself. The tray contains two placeholders, one for the cuvette called as Strivette and the second for an optically clear strip. The second placeholder functions to calculate the scattering of light caused solely due to the optically clear strips used in the body of the Strivette. The fluid is drawn into the cuvette by capillary action. When this fluid filled Strivette is placed in the Strivette holder, the light transmitted through the sample is predefined and depending on the light absorbed by the fluid sample rest of the light is transmitted through the sample and detected by the photosensor. Using the value obtained by the photosensor the fluid component value is calculated. The sample is exposed to each LED alternatively for a defined period of time i.e. ~10ms each. According to a preferred embodiment of the present invention the light absorbance is measured considering the two LED wavelengths and the photosensor calculates, according to a programmed algorithm, the total level of fluid component.

In one embodiment of the present invention, where the fluid to be tested is whole blood, the method of measuring a blood sample involves obtaining the sample by pricking the patient using the lancets and lancing pen provided in the device packaging. It is advised to wipe off the first drop obtained after pricking the patient. A small drop of ~ 8uL whole blood is drawn into the Strivette using its capillary action. Blood should completely fill the Strivette to obtain the correct value if partially filled, machine will give erroneous readings.
In another embodiment of the present invention, where the fluid to be tested is urine, the method of measuring the sample involves obtaining the sample by collecting the urine in a cup followed by contacting the collection tip of the cuvette with the surface of the collected urine, the capillary action of the cuvette sucks the urine into the cuvette cavity void of any bubbles. A small drop of ~8uL is collected for examination.

The device is powered and to initiate the testing process, the tray is opened which is auto detected by the machine. When the tray is opened machine starts to calibrate, here each time tray is opened machine calibrates itself and achieves a predefined intensity. During the calibration process device should be protected from external interference such as motion. Once calibration is completed, the blood filled Strivette containing fluid is placed in the depression given in the tray and the tray is then closed for measurement. The machine performs necessary measurements and results i.e. fluid content measurement will be displayed. The duration of the measurement, unit of the measurement will be dependent on the fluid under measurement.

In an embodiment of the present invention, the device for measurement of fluid component such as hemoglobin in whole blood, HCG in urine, WBC in whole blood etc.; without any dilution or reagent intervention in easy steps where there is no need of professionally trained personnel for performing test is disclosed. The invention concerns to provide a device which can be used to determine fluid component levels at lower cost.

UTILITY
The device according to the present invention is smart, compact and portable. It does not require laboratory trained persons to operate the device. It may be used by a normal untrained individual. While the foregoing body explains the various benefits of the present invention below are additional benefits of using device of present invention:
1] To provide a device for quick and accurate results by simplifying handling of blood and other body fluids using proprietary cuvette (Strivettes) which are free of any reagents, disposable, cost efficient, compact, use small volume of blood and allow testing on arterial and / or venous whole blood amongst other fluids.
2] To provide a device which runs on an algorithm based on transmittance photometry where absorbance by blood is correlated with actual hemoglobin.
3] To provide quick, accurate, easy process for measurement of hemoglobin in arterial and / or venous whole blood.
4] To provide a device wherein the distance between the LED source and the photosensor may be adjusted to achieve a lower path length.
5] To provide a device for measuring fluid components that uses lower intensities of the LED so that less power is consumed.
The foregoing description of the invention has been set merely to illustrate the invention and is not intended to be limiting. Since modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to person skilled in the art, the invention should be construed to include everything within the scope of the disclosure.

EXAMPLES
Example 1
Device was turned on and receiving tray was pulled out to initiate calibration;
An optically clear strip was placed in as control into one placeholder and a Strivette containing ~ 8uL of whole blood to be tested was placed in the other placeholder of the receiving tray;
After calibration, the receiving tray was closed and the sample was exposed to LED wavelengths of 550nm as first wavelength and 850nm as the second wavelength, alternatively for a period of ~10ms each;
The whole blood appeared to be light colored ( lighter red color instead of red), indicating that the hemoglobin level in the blood was low. For this reason, the intensity of the wavelengths considered was lowered to a single intensity and the readings were taken.
The light absorbance by the whole blood of the two wavelengths was measured by the photosensor according to a preprogrammed algorithm which calculated the true absorbance of the blood after subtracting the turbidity amongst other deviation/scattering components as measured using the optically clear strip (as control, not containing any fluid).
The hemoglobin was calculated to be 12g/dL by the algorithm based on the output of the photosensors and the same was communicated to the user by means of Bluetooth on the user’s phone;
The device also offered the user to use the display screen (14) of Fig 1 & 4 and onboard interface such as buttons (13) of Fig. 1& 4located on the external body of the device.
Example 2
Device was turned on and receiving tray was pulled out to initiate calibration;
An optically clear strip was placed in as control into one placeholder and a Strivette containing ~ 10uL of serum to be tested was placed in the other placeholder of the receiving tray;
After calibration, the receiving tray was closed and the sample was exposed to LED wavelengths of 400nm as first wavelength and 550nm as the second wavelength, alternatively for a period of ~10ms each;
The serum appeared to be dark colored (dark yellow instead of light yellow/cream), indicating that the bilirubin level in the serum was high. For this reason, the intensity of the wavelengths considered was increased to a triple intensity and the readings were taken.
The light absorbance by the serum of the two wavelengths was measured by the photosensor according to a preprogrammed algorithm which calculated the true absorbance of the serum after subtracting the turbidity amongst other deviation/scattering components as measured using the optically clear strip (as control, not containing any fluid).
The bilirubin level was calculated to be 1.2mg/dl by the algorithm based on the output of the photosensors and the same was communicated to the user by means of Bluetooth on the user’s apple tablet;
The device also offered the user to use the display (14) of Fig 1 & 4 screen and onboard interphase such as buttons (13) of Fig. 1 & 4 located on the external body of the device.

EXPERIMENTAL DATA
? Temperature Test & Humidity Test
Temperature and humidity testing were done for device of the present invention (also referred to as HbChek devices). Specification of standards / Equipment used: Stability Chamber Tempo. Wherein devices were exposed to various temperature ranges and humidity ranges.

It was observed that the device under test (HbChek) was found to be in fully operational condition when exposed to various temperatures (0?C -50?C) and humidity ranges (up to 95%)
? Accuracy & Effectiveness Test
An evaluation to measure the effectiveness and accuracy of the device of the present invention (called HbChek) was conducted. The study was carried out in an NABL accredited “Millennium Path Lab”, Thane, Mumbai. The evaluation comprised of 476 samples with a hemoglobin range of 4.5 to 18.1 g/dL. The person’s correlation coefficient of the device of the present invention versus the reference laboratory method (Sysmex XN 1000) was found to be 0.98 indicating strong correlation. Based on the statistical analysis, more than 95% readings of the present invention were within ± 0.9 g/dL proving its suitability to be used as a hemoglobin testing device.

,CLAIMS:
Claim 1. A compact and portable device to measure the total component level in fluids based on transmittance photometry comprising:
Light source with at least two wavelengths;
At least a photosensor;
A receiving tray including at least two placeholders;
At least a transparent control strip and a cuvette,both having flat configuration;
A pre-programed, self-calibrating algorithm uploaded into the device;
A display screen; and
Onboard interface(s), all connected to a portable user interface by means of a wireless communication
Claim 2. The device as claimed in claim 1, wherein the light source preferably comprises at least two LEDs having different wavelengths each emitted alternatively for a defined period of time i.e. ~10ms such that the first wavelength measures the absorbance of the fluid component while the second wavelength measures the fluid turbidity.
Claim 3. The device as claimed in claim 1, wherein the photosensormay be a photodiode or such other photosensor which senses light having a wavelength ranging from 400nm to 1100nm and is optically aligned with the light source, transparent control strip and cuvette
Claim 4. The device as claimed in claim 1, wherein the photosensor senses light having a wavelength ranging from 500-600nm and 800-980nm as the first and second wavelengths respectively, for measuring contents of blood sample, preferably for Hemoglobin measurement & turbidity correction; and a wavelength ranging from 400-500nm and 550-650nm as the first and second wavelengths respectively, for measuring contents of a serum sample, preferably for Bilirubin measurement& turbidity correction.
Claim 5. The device as claimed in claim 1, wherein the device the device is made of materials selected from but not limited to plastic, stainless steel, or a combination thereof and measures a maximum of 93mm x 141mm, the cuvette holder measures 30mm x 9mm having a maximum thickness of 0.3mm more than the proprietary cuvette named Strivette;
Claim 6. The device as claimed in claim 1, wherein the device is capable of measuring component level in fluids including but not limited to whole blood, serum, urine, saliva, amongst other fluids by accommodating an appropriate wavelength and intensity of LED according to the selected sample to be measured
Claim 7. The device as claimed in claim 1, wherein the portable user interface may be selected from but not limited to a mobile phone, a tablet, a computer, inter alia and the wireless communication may be selected from but not limited to Bluetooth, WiFi connection, internet connection, or such other wireless communication.
Claim 8. The device as claimed in claim 1, wherein the intensity of the light source may be adjusted based on the absorbance capacity of sample fluid.
Claim 9. A methodto quantitatively measure the total component level in fluids comprising:
Device is turned on and receiving tray is pulled out to initiate calibration;
Placing an optically clear strip as control in one placeholder and a Strivette containing fluid to be tested in the other placeholder of the receiving tray;
Once calibrated, the receiving tray is closed and the sample is exposed to two LED wavelengths alternatively for a period of ~10ms each
The light absorbance by the fluid of the two wavelengths is measured by the photosensor according to a preprogrammed algorithm
The fluid component is calculated by the algorithm based on the output of the photosensors and the same is communicated to the user by means of a user interface
Claim 10. The methodas claimed in claim 9, wherein the absorbance readings of the wavelength is detected by the photosensor and considered by the algorithm in calculating the true absorbance of the fluid after subtracting the fluid turbidity amongst other deviation/scattering components, to accurately quantify the fluid component value. The device runs on algorithm based on transmittance photometry where absorbance by fluid is correlated with actual fluid component.