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Extreme Point of Care Diagnostics on a CD

Primary Information

Domain

Environmental Science & Climate Change

Project No.

8058

Sanction and Project Initiation

Sanction No: F. No.: 35-10/2016-TS-I

Sanction Date: 27/02/2017

Project Initiation date: 24/03/2017

Project Duration: 36 months

Partner Ministry/Agency/Industry

Ministry of Human Resource Development (MHRD)

Indian Council of Medical Research (ICMR)

Principal Investigator

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Suman Chakraborty
Department of Mechanical Engineering, IIT Kharagpur

Co-PIs

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Chandra Shekhar Sharma
Department of Chemical Engineering, IIT Hyderabad

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Dipankar Bandyopadhyay
Department of Chemical Engineering, IIT Guwahati

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Chirasree RoyChaudhuri
Indian Institute of Engineering Science and Technology, Shibpur

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Dipayan Sanyal
CSIR-Central Glass & Ceramic Research Institute

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Dr. Satadal Saha
Foundation for Innovations in Health and JSV Innovations Private Limited, Kolkata

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Marc J. Madou
University of California, Irvine, USA

Host Institute

 

Scope and Objectives

Developing WiFiCD microfluidics platform as diagnostic tool.

Integration with sensing and detection strategies, smart power source and thus the environmental challenges will be taken care of.

Commercial prototype development

Field trials for testing and benchmarking with standard pathological laboratory reports

Deliverables

Electrochemical detection of diseases on a spinning disk (CD).

A portable platform for disease detection.

Scientific Output

1) Fabrication of carbon electrodes using conventional UV photolithography to pattern SU-8 structure and one step conversion of SU-8 to glassy carbon upon pyrolysis.
2) Selective detection of Hep-B surface antigen in high ionic strength buffer using monoclonal antibodies with a sensitivity of 40% and detection range of 1pM.
3) Carbon thin films electrodes on stainless steel (SS) wafers deposited by spin coating SU-8 followed by controlled pyrolysis .
4) Maskless fabrication of interdigitated (IDT) electrodes completed. Series of studies undertaken to establish the optimal parameters for fabrication.
5) The IDT electrodes were carbonized under controlled atmosphere to accomplish significantly reduced shrinkage on using SU-8 photoresist in comparison to the traditional acrylate photoresists.
6) Fabricated SU8 derived Carbon thin films on silicon (Si) and stainless steel (SS) wafer for Electrochemical Sensing Applications.
7) Fabricated SU8 patterns using photolithography followed by controlled pyrolysis in inert environment to yield three dimensional high aspect ratio carbon IDEAs.

Results and outcome till date

1) Fabrication of carbon electrodes using conventional UV photolithography to pattern SU-8 structure and one step conversion of SU-8 to glassy carbon upon pyrolysis.
2) Selective detection of Hep-B surface antigen in high ionic strength buffer using monoclonal antibodies with a sensitivity of 40% and detection range of 1pM.
3) Carbon thin film electrodes on stainless steel (SS) wafers deposited by spin coating SU-8 followed by controlled pyrolysis, for Electrochemical Sensing Applications.
4) Maskless fabrication of interdigitated (IDT) electrodes completed. Series of studies undertaken to establish the optimal parameters for fabrication.
5) The IDT electrodes were carbonized under controlled atmosphere to accomplish significantly reduced shrinkage on using SU-8 photoresist in comparison to the traditional acrylate photoresists.
6) Fabricated SU8 patterns using photolithography followed by controlled pyrolysis in inert environment to yield three dimensional high aspect ratio carbon IDEAs. Output photos.
7) Electrochemical characterization of carbon electrodes using potassium ferrocyanide in potassium chloride with three electrode system revealed that pyrolysis at 1000 Celsius yeilded the highest CV response.
8) An investigation of selectivity and long term stability of the electrode revealed that a current change within 6% upon exposure to Hep-C antigen and a drift in the CV plots over a period of 4 weeks, both indicate robust performance.
9) A real time analysis of the electrode reveals a response time of 20 sec for serum and 25 sec for the whole sample, as compared to 5 sec for just the electrolyte solution.
10) Activated carbon ink was prepared and used for fabrication of Carbon-IDEAs by drop-on-demand deposition method by Dimatix DMP 2831 printer on a quartz substrate of dimension 50 mm x 20 mm x 1 mm.
11) Fabrication of microfluidic channels: T-sensors (T-channels) and Y-sensors (Y-channels) were fabricated using a maskless laser lithographic process chain for measurement of concentration, diffusivity and reaction kinetics.
12) Carbonisation of the structures: Carbonisation of the microfabricated photoresist structures was carried out at high temperature furnaces under controlled atmosphere following a slow ramp for heating and cooling to prevent excessive thermal stresses and adequate dwell time for ensuring completion of carbonisation. The carbonised structures exhibited some shrinkage with respect to the original pre-carbonised structure. For example, for a triangular structure, 6-7% shrinkage was observed after carbonisation.
13) Characterization of material properties of IDEAS: The characterisation of the carbonised structures was performed using FESEM, XRD, Raman spectroscopy and X-ray photoelectron spectroscopy. The XRD data and X-ray photoelectron spectroscopy study confirms the presence of glassy carbon structures. Raman spectroscopy confirmed the presence of graphitic structure along with data on its structural integrity.
14) Electrical Characterization of IDEAS: The electrical characterisations were carried out using high-current interactive source meter instrument (Model- Keithley 2460). As per the requirement of low power operation for EPOCs, high conductive carbon is on high demand. Towards this goal, the electrical and electrochemical properties of the carbonised photoresists were characterised for the fabricated carbon electrode. The Current-Voltage curve established the proportional increase of current with the applied voltages. The electrochemical measurement yielded the cyclic current-voltage curve with a prominent redox peak, thus confirming the appropriate electrochemical potential window.
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Societal benefit and impact anticipated

The disease diagnostic facilities, currently available, do not address majority of the concerns of developing countries, like India. Moreover, the available healthcare facilities are inaccessible to the rural and economically backward population. Furthermore, the standard laboratory-based diagnostic protocols are labor intensive, time consuming, require elaborate infrastructure, and expert on-field pathologists. Hence, in resource-limited settings, such elaborate and expensive diagnostic procedures are prohibitive against access to quality healthcare. The resource limited settings, extreme environmental conditions and lack of trained staff pose serious challenge to provide comprehensive primary healthcare that include timely diagnosis of communicable diseases. It has now been realized that innovative, low cost but effective point-of-care diagnostic technologies may be a solution in this direction with significant humanitarian, social and economic benefits. Such disruptive paradigm of alterative diagnostics has direct social implications. For example, it is estimated that one third of the maternal deaths in India occur due to anaemia. This can be corrected through iron-folic acid supplementation through a primary care centre. Technology of disease detection by loading one drop of body fluid on a rotating platform, for the benefit of ailing rural population, has evolved substantially in recent past as an alternative diagnostic strategy, with a potential of addressing many challenges in under-resourced clinic settings. Our unique innovation of electrochemical detection on a spinning disc, in that perspective, may completely revolutionize the diagnostic techniques employed in extreme point of care settings of the developing world. Transfer of this technology for potential commercialization is currently under way.

Next steps

Scaling up of the technology for mass fabrication.

More elaborate validation with clinical standards.

Addressing regulatory approval issues.

Publications and reports

1. Rahul Agarwal, Arnab Sarkar, and Suman Chakraborty. "Interplay of Coriolis Effect with Rheology Results in Unique Blood Dynamics on a Compact Disc." Analyst (2019).
2. Sagnik Middya, Mitradip Bhattacharjee, Nilanjan Mandal, and Dipankar Bandyopadhyay, "RGO-Paper Sensor for Point-of-Care Detection of Lipase in Blood Serum." IEEE Sensors Letters, 2018. 4: p. 1-4. (DOI: 10.1109/LSENS.2018.2849418)
3. Mitradip Bhattacharjee and Dipankar Bandyopadhyay, "Flexible Paper Touchpad for Parkinson's Hand Tremor Detection", Sensors and Actuators A: Physical, 2019 (accepted).
4. Mitradip Bhattacharjee, Siddharth Thakur and Dipankar Bandyopadhyay, Acoustic wave mediated microdroplet based blood urea detection for point of care testing, ACS Sustainable Chemistry and Engineering, 2019 (accepted).
5. Mitradip Bhattacharjee,a Sagnik Middya,a and Dipankar Bandyopadhyay, Point-of-Care Stress Detection of Muscles Using a Flexible Surface Potential Measurement Prototype, Medical Devices and Sensors, 2019 (accepted).
6. Shirsendu Mitra, Nirmal Roy, Surjendu Maity, Dipankar Bandyopadhyay, Multimodal Chemo-Magneto-Taxes of 3G CNT-bots to Power Fuel Cells, (Manuscript Submitted), 2019.
7. Mitradip Bhattacharjee, Sagnik Middya, Joydip Chaudhuri and Dipankar Bandyopadhyay, "Droplet Based Detection of Blood alpha-Amylase Employing Thermal Marangoni Effect", (Manuscript under Preparation).
8. D.Mondal, M. Suresh, Chandra S. Sharma, A.Singha, C.RoyChaudhuri "Optimization of carbon electrodes for electrochemical biosensors: influence of thickness on redox output", Materials Today: Proceedings, 2018 (accepted).
9. J. Basu and C. RoyChaudhuri "Graphene Nanoporous FET Biosensor: Influence of Pore Dimension on Sensing Performance in Complex Analyte" IEEE Sensors Journal, Volume: 18 , Issue: 14 , pp. 5627-5634, 2018.
10. R.Ray, J.Basu, W.A. Gazi, N.Samanta, K.Bhattacharyya and C.RoyChaudhuri Senior Member, IEEE "Label Free Biomolecule Detection in Physiological Solutions with Enhanced Sensitivity using Graphene Nanogrids FET Biosensor", IEEE Transactions on NanoBioscience, Volume: 17 , Issue: 4 , pp. 433-442, 2018
11. Bidhan Pramanick, Naresh Mandal, Debasis Mondal, Chirasree RoyChaudhuri, Suman Chakraborty "C-MEMS Derived Glassy Carbon Electrodes as Sensitive Electrochemical Biosensors" IEEE sensors Conference 2018, October 28-31, 2018, pp. 1142-1145 New Delhi, India.
12. N.Mandal, J.Basu, C.RoyChaudhuri "Nanostructured Graphene FET Biosensor Using Coplanar Gate Electrode for Point-of-Care Application", Fourth International Meeting entitled "Carbon MEMS: New Horizons" , December 05-07,2018, IIT Hyderabad, India

Patents

1) Three-glassy carbon-electrode based device for impedance measurement of whole blood and its constituents, B. Pramanick, S. Biswas, V. Pakira, S. Chakraborty, patent file submitted in 2017 at IIT Kharagpur (under review).
2) Electrochemical detection on a spinning disc. B. Pramanick, S. Biswas, V. Pakira, Naresh Mandal, Chirasree Roy Chaudhuri, Satadal Saha, Marc Madou, S. Chakraborty. Applied for filing patent at IIT Kharagpur (under review).

Scholars and Project Staff

IIT Kharagpur
1) Dr. Bidhan Pramanick (Postdoctoral Fellow) has completed one year in the position and resigned in June, 2018.
2) Dr Sudip Chattopadhyay (Postdoctotal fellow, May 2019 joining).
3) Mr. Rahul Agarwal (Junior Research Fellow, July-2017 onwards)

IIT Guwahati
4) Mr. Sagnik Middya appointed (Junior Research Fellow)

IIT Hyderabad
5) Poonam Rani (JRF, 26 July 2016-till date)
6) Ahsana Sadaf (Project Assistant, 7 Sept 2017-till date)
7) Sushree Ritu Ritanjali (JRF, 29 Sept 2017-26 Dec 2017)

IIEST Shibpur
8) Mr. Anant Kumar Singh (Junior Research Fellow) was appointed but he has left. A new research scholar is to be appointed.
9) Mr. Surajit Bose (Technical Assistant) CGCRI Kolakata
10) Data not available JSV Innovations
11) Program head-1
12) KIOSK co-ordinator-1
13) Back-end doctor-1
14) Health assistants-5

Challenges faced

 

Other information

Amount utilized for 'consumables, contingency, travel and overheads' is reflected under 'amount utilized for other expenses'.

Financial Information

  • Total sanction: Rs. 37880800.00 lakhs

  • Amount received: Rs. 28918000.00 lakhs

  • Amount utilised for Equipment: 6009825.00 lakhs

  • Amount utilised for Manpower: Rs. 6587037.00 lakhs

  • Amount utilised for Consumables: 0

  • Amount utilised for Contingency: 0

  • Amount utilised for Travel: Rs. 0

  • Amount utilised for Other Expenses: Rs. 7120632.00 lakhs

  • Amount utilised for Overheads: 0

Equipment and facilities

Main equipment purchased, facilities created IIT Kharagpur
1) Rotational Spin Stand IIT Guwahati
2) Dual channel Source Meter Unit, Keithley 2614B
3) Thermal Imager
4) Purchase order issued for a High voltage AC/DC power supply
5) Indent raised for Portable UV spectrometer
6) Indent raised for UV light source/Xenon lamp IIT Hyderabad
7) High Temp. Furnace: Carbolite Furnace from M/s. Carbolite Gero GmbH
8) Battery Analyzer BCS 805 from Bio Logic Science Instruments. IIEST Shibpur
9) Potentiostat CGCRI Kolkata
10) Purchase procedure is in process JSV innovations
11) Desktop PC- 6 Nos
12) ECG system- 2Nos.
13) Pulse oximeter- 2 Nos.
14) Generator set- 2 Nos.
15) UPS- 2 Nos.
16) Modem etc- 2 set
17) Stethoscope- 4 Nos.
18) BP (Auto)- 2 Nos.
19) BP (Manual)- 2 Nos.
20) Accuchak- 2 Nos.
21) Thermometer, height, weight machines etc- 2 set
22) Printer- 2 Nos.
23) Mobile set- 2 Nos.
24) Tablet PC- 4 Nos.
25) Furniture/patient examination table etc - 2 set Facilities created:

IIT Kharagpur
1) CD fabrication facility
2) CD rotating platform
3) Carbon-MEMS facility

IIT Hyderabad
4) Pyrolysis IIEST Shibpur
5) Electrochemistry JSV innovations
6) 2 Nos. rural health KIOSK
7) Software for interfacing the backend doctors in city with the health-assistants and patients in rural remote area