Minimally invasive Mobile Healthcare Diagnostic platform for Glycated Hemoglobin Detection
Primary Information
Domain
Nano-Technology Hardware
Project No.
5699
Sanction and Project Initiation
Sanction No: F. No. 35-2l 2018-T.S.-I
Sanction Date: 20/01/2017
Project Initiation date: 23/03/2017
Project Duration: 36
Partner Ministry/Agency/Industry
INDIAN COUNCIL OF MEDICAL RESEARCH (ICMR)/ Achira Labs Pvt. Ltd
Role of partner:ICMR is funding 50% of the project grant. Achira Labs PVT ltd is our industry partner. They are helping us in execution of the project and marketing of the project
Support from partner:Our Partner Achiralabs is helping us in the device fabrication. They have the wax printer with them. All the devices are being made there with the help of our staff.
Principal Investigator
Siva Rama Krishna Vanjari
Indian Institute of Technology, Hyderabad
Host Institute
Co-PIs
Sumohana Channappayya
Indian Institute of Technology, Hyderabad
Anshika Agarwal
Indian Institute of Technology, Hyderabad
Scope and Objectives
Development of paper based colorimetric sensors for Hb. This is envisaged to be used as triaging tool for anemia Development of image processing algorithms for color constancy Development of image processing algorithms for extracting Hb concentration Optimization of pH dyes concentration to develop unique dye combination to detect pH changes occurring during binding of boronic acid with GHb Synthesis of pH sensitive nanofibers - Immobilization of optimized pH dyes concentration in the nanofibers using electrospinning Modification of pH sensitive nanofibers with boronic acid compounds Development of paper based colorimetric sensor for GHb. Porting the image processing algorithms onto mobile platform
Deliverables
The project deals with the deals with the development of Mobile integrated paper based platform for detecting glycated hemoglobin. Glycated Hemoglobin is a variant of hemoglobin. Hemoglobin present in Red blood cells react slowly with the glucose over a period of 120 days to form glycated hemoglobin. This reaction is referred to as non enzymatic , for, there are no biocatalysts involved in this particular reaction. Since the reaction happens over 120 days the percentage of glycated hemoglobin over the total hemoglobin gives an average value of sugar over the past 120 days. Glycated Hemoglobin also referred to as GHb or Hba1C is always expressed as a percentage of hemoglobin. To develop a sensor for hemoglobin, we need to develop two sensors and take their ratio and express it as a percentage. The first sensor is for glycated hemoglobin itself and the second sensor is for total haemoglobin or haemoglobin. The second sensor in itself can be used independently to detect anaemia. So the key deliverable include sensors for glycated hemogloblin and hemoglobin
Scientific Output
The project deals with the development of haemoglobin and glycated haemoglobin sensors using paper based device and a mobile. It is an accepted WHO practise to figure out the concentration of Hb using the intensity of drop of blood put on a blotting paper. Taking it further, our idea is to develop a paper where the drop of blood is spread uniformly. A picture of that would then be analysed using a mobile based image platform to figure of the concentration. The key challenge is to restrict the drop of blood to a precisely defined area. To achieve this, we print wax on a filter paper using a wax printer in certain regions. Wax inherently is hydrophobic. It hates water. It does not allow any water or in our case drop to spread. A circular region is defined where there is no wax and the rest of the region is surrounded by wax. The drop stays in circular region only. Furthermore, the circular region is modified with a lysing agent and surfactant. Lysing agent breaks RBCs and releases Hb. Surfactants are inherently hydrophilic in nature. They assist in spreading the drop uniformly. The structure of Hb paper device is as follows. It contains a filter paper with a predefined area for dropping the blood and wax coating that prevents the drop from spreading everywhere else. Multiple standard colors are used in wax printing. These colors act as reference colors for image processing. The key in image processing is to take care of variations in surrounding illuminations and intensities. A set of algorithms are being developed/utilized for these purpose. Beneath the filter paper is an absorption pad. This takes out the excess volume of blood. Beneath the absorption pad and above the filter paper are PVC pad and lamination sheet respectively. These are used for providing the paper enough mechanical strength and for the prevent of degradation of colors. All the user needs to do is to put a drop of blood and take an image using the app being developed. (slides 2 to 9) For glycated haemoglobin, the device structure is exactly the same. The only difference here is the circular area is also modified with pH sensitive, boronic acid modified nanofibers. Glycated Hemoglobin specifically binds to boronic acids. Moreover, this binding leads to slight pH change. This pH change is proportional to the concentration of glycated haemoglobin. The pH change can be detected using pH dye embedded nanofibers. Nanofibers are synthesized using a well known electrospinning techniques. When a polymer droplet coming out of small syringe is subjected to high electric field, nanofibers jet out once surface tension forces are overcome by electric field. These can be collected onto any surface. The polymer droplet in the present case, consists of pH sensitive dyes and boronic acid molecules. These get embedded into the nanofibers. The primary advantage of nanofibers is that it has high surface to volume ratio. Thus the chemical reactivity of the surface is far superior and hence they are highly sensitive. In the present case we have developed pH sensitive nanofibers for detecting glycated haemoglobin.
Results and outcome till date
Prototype for Hemoglobin detection is completed. Validation phase is on-going Initial results of Glycated Hemoglobin detection are achieved. Optimization is under progress
Societal benefit and impact anticipated
The only way to avoid all the secondary effects of uncontrolled diabetes is to monitor glycemic index and keep diabetes under control. Though blood glucose levels is a very good diagnostic indicator for diabetes, their levels vary day by day depending on the life style of the individuals. Glycated Hemoglobin (GHb), modification of hemoglobin with glucose and is a very good biomarker that indicates the average value of blood glucose over the past 120 days. It is always expressed as a percentage of total hemoglobin (Hb) present in blood. GHb is regarded as the gold standard for monitoring diabetes. Remote healthcare is thrust for this decade. Mobile technology will play an important role in achieving the same. A combination of mobile based image processing and colorimetric biosensors opens a new avenue for diagnosing biomarkers of relevance remotely thus paving way for next generation remote healthcare. Keeping this in view, we are in the process of developing colorimetric based sensors integrated with mobile ported image processing apps for GHb and Hb. The vision is to create a very simple device and app which can be used by any unskilled person. Specifically for Hb, we envision to create a traiging tool for screening of anemia. we believe screening of anemia is an extremely important aspect in rural health care.
Next steps
Hemoglobin Sensor is in validation phase. Glycated Hemoglobin Sensor is under development. We expect to complete the development by March 2019. Alternatively we are exploring other ways of detecting glycated hemoglobin sensor as suggested by initial review committee
Publications and reports
The work is envisioned to be a product and hence we dont intend to publish any data
Patents
The technology is simple. We would file a patent at an appropriate time.
Scholars and Project Staff
Dr. Anshika Agarwal, Research Associate,May 2017- Jan 2018 Manish Kumar,Project Assistant,Sep 17-Jan 18 Rahul Gangwar, Project Assistant,Sep 2017- July 2018 Rajesh Surireddi, Intern, Nov 2017-June 2018 Rajesh Surireddi,Project Assistant, July 2018 -Present Dr. Jose Joseph,Research Associate,Feb 2018 -Sep 2018 Gayatri Srujana, Project Associate, Aug 2018 - Present Aditya Bhagavathi, Intern - October 2018 - Present
Challenges faced
inconsistent manpower
Financial Information
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Total sanction: Rs. 97.80 lakhs
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Amount received: Rs. 62.70 lakhs
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Amount utilised for Equipment: Rs. 9.36 lakhs
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Amount utilised for Manpower: Rs. 19.94 lakhs
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Amount utilised for Consumables: Rs. 9.41 lakhs
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Amount utilised for Contingency: Rs. 0.74 lakhs
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Amount utilised for Travel: Rs. 1.51 lakhs
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Amount utilised for Other Expenses: 0
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Amount utilised for Overheads: Rs. 10.45 lakhs
Equipment and facilities
Fume Hood, Microcentrifuge, Hot air oven, Workstation
