“AMBULET” is an interactive gateway for relaying physiological parameters and video data between mobile ambulances and the health practitioners/hospitals. Nearly 51% of accident–related deaths occur due to inadequate medical attention during transportation to the hospital. AMBULET supports multiple streams of multiplexed real-time data transport using associated application proxies over a set of bonded channels to transparently and dynamically maintain desired levels of service quality over the cellular communications infrastructure.
In this project, we developed an “imaging” based point-of-care diagnostic device, which can fully-automate the complete work flow of conventional clinical microscopy. A custom designed portable digital microscope augmented with dedicated microfluidic lab-on-chips enables process automation, as well as, cost effective implementation of microscopic diagnosis of malaria. Such an inexpensive, portable and easy-to-use diagnostic device, which requires minimal skilled human intervention, greatly enhances the quality of health-care available to the rural population of the world.
| 1. | Srinivasan, Rajesh; Umesh, Sharath; Murali, Swetha; Asokan, Sundarrajan; Gorthi, Sai Siva Bare Fiber Bragg grating immunosensor for real‐time detection of Escherichia coli bacteria Journal Article Journal of Biophotonics, 10 (2), pp. 224-230, 2017. Abstract | BibTeX | Links:   @article{Srinivasan2017,
title = {Bare Fiber Bragg grating immunosensor for real‐time detection of Escherichia coli bacteria },
author = {Rajesh Srinivasan and Sharath Umesh and Swetha Murali and Sundarrajan Asokan and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/Srinivasan_et_al-2016-Journal_of_Biophotonics.pdf},
doi = {10.1002/jbio.201500208},
year = {2017},
date = {2017-02-28},
journal = {Journal of Biophotonics},
volume = {10},
number = {2},
pages = {224-230},
abstract = {Escherichia coli (E. coli) bacteria have been identified to be the cause of variety of health outbreaks resulting from contamination of food and water. Timely and rapid detection of the bacteria is thus crucial to maintain desired quality of food products and water resources. A novel methodology proposed in this paper demonstrates for the first time, the feasibility of employing a bare fiber Bragg grating (bFBG) sensor for detection of E. coli bacteria. The sensor was fabricated in a photo‐sensitive optical fiber (4.2 µm/80 µm). Anti‐E. coli antibody was immobilized on the sensor surface to enable the capture of target cells/bacteria present in the sample solution. Strain induced on the sensor surface as a result of antibody immobilization and subsequent binding of E. coli bacteria resulted in unique wavelength shifts in the respective recording of the reflected Bragg wavelength, which can be exploited for the application of biosensing. Functionalization and antibody binding on to the fiber surface was cross validated by the color development resulting from the reaction of an appropriate substrate solution with the enzyme label conjugated to the anti‐E. coli antibody. Scanning electron microscope image of the fiber, further verified the E. coli cells bound to the antibody immobilized sensor surface. },
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Escherichia coli (E. coli) bacteria have been identified to be the cause of variety of health outbreaks resulting from contamination of food and water. Timely and rapid detection of the bacteria is thus crucial to maintain desired quality of food products and water resources. A novel methodology proposed in this paper demonstrates for the first time, the feasibility of employing a bare fiber Bragg grating (bFBG) sensor for detection of E. coli bacteria. The sensor was fabricated in a photo‐sensitive optical fiber (4.2 µm/80 µm). Anti‐E. coli antibody was immobilized on the sensor surface to enable the capture of target cells/bacteria present in the sample solution. Strain induced on the sensor surface as a result of antibody immobilization and subsequent binding of E. coli bacteria resulted in unique wavelength shifts in the respective recording of the reflected Bragg wavelength, which can be exploited for the application of biosensing. Functionalization and antibody binding on to the fiber surface was cross validated by the color development resulting from the reaction of an appropriate substrate solution with the enzyme label conjugated to the anti‐E. coli antibody. Scanning electron microscope image of the fiber, further verified the E. coli cells bound to the antibody immobilized sensor surface. |
| 2. | Daniel, Kiruba S C G; Julius, Lourdes Albina Nirupa; Gorthi, Sai Siva Instantaneous detection of melamine by interference biosynthesis of silver nanoparticles Journal Article Sensors and Actuators B: Chemical, 238 , pp. 641-650, 2017. Abstract | BibTeX | Links: @article{Daniel2017b,
title = {Instantaneous detection of melamine by interference biosynthesis of silver nanoparticles},
author = {S. C. G. Kiruba Daniel and Lourdes Albina Nirupa Julius and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/1-s2.0-S092540051631156X-main.pdf},
doi = {10.1016/j.snb.2016.07.112},
year = {2017},
date = {2017-01-31},
journal = {Sensors and Actuators B: Chemical},
volume = {238},
pages = {641-650},
abstract = {Instantaneous detection of melamine, a potential milk adulterant has been demonstrated at room temperature by means of interference biosynthesis of silver nanoparticles. The sensing mechanism is based on the colorimetric change observed during the synthesis of silver nanoparticles due to the presence of melamine added during the biosynthesis. Presence and absence of melamine led to either inhibition of nanoparticle formation or enable partial synthesis of nanoparticles which is detected spectrally. A limit of detection (LOD) of 0.1 ppm in water and 0.5 ppm in raw milk was detected by the proposed technique at room temperature. UV–vis spectroscopy and High Resolution Transmission Electron Microscopy (HR-TEM) have been used to detect the spectral Surface Plasmon Resonance (SPR) and morphological changes of synthesized silver nanoparticle with and without the presence of the analyte melamine. Further, interference synthesis based sensing of melamine was done with caffeic acid as a reducing agent which confirms the role of caffeic acid a major constituent of Parthenium leaf extract for interference biosynthesis based sensing. Melamine is detected from raw milk by interference biosynthesis based sensing after a facile milk pre-processing step. Thus the method can be converted into a workable handheld prototype for detection of melamine for in-situ field applications.},
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Instantaneous detection of melamine, a potential milk adulterant has been demonstrated at room temperature by means of interference biosynthesis of silver nanoparticles. The sensing mechanism is based on the colorimetric change observed during the synthesis of silver nanoparticles due to the presence of melamine added during the biosynthesis. Presence and absence of melamine led to either inhibition of nanoparticle formation or enable partial synthesis of nanoparticles which is detected spectrally. A limit of detection (LOD) of 0.1 ppm in water and 0.5 ppm in raw milk was detected by the proposed technique at room temperature. UV–vis spectroscopy and High Resolution Transmission Electron Microscopy (HR-TEM) have been used to detect the spectral Surface Plasmon Resonance (SPR) and morphological changes of synthesized silver nanoparticle with and without the presence of the analyte melamine. Further, interference synthesis based sensing of melamine was done with caffeic acid as a reducing agent which confirms the role of caffeic acid a major constituent of Parthenium leaf extract for interference biosynthesis based sensing. Melamine is detected from raw milk by interference biosynthesis based sensing after a facile milk pre-processing step. Thus the method can be converted into a workable handheld prototype for detection of melamine for in-situ field applications. |
| 3. | Daniel, Kiruba S C G; Julius, Lourdes Albina Nirupa; Gorthi, Sai Siva Microfluidics based handheld nanoparticle synthesizer Journal Article Journal of Cluster Science, 28 (3), pp. 1201-1213, 2017. Abstract | BibTeX | Links: @article{Daniel2017,
title = {Microfluidics based handheld nanoparticle synthesizer},
author = {S. C. G. Kiruba Daniel and Lourdes Albina Nirupa Julius and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/KirubaDaniel2017_Article_MicrofluidicsBasedHandheldNano.pdf},
doi = {10.1007/s10876-016-1120-x},
year = {2017},
date = {2017-05-31},
journal = {Journal of Cluster Science},
volume = {28},
number = {3},
pages = {1201-1213},
abstract = {Current study relates to the development of an electrical power-free, handheld microfluidic nanoparticle synthesizer for synthesis of uniform sized silver nanoparticles at room temperature. The synthesizer module consists of a custom designed microreactor and employs negative pressure based pumping mechanism for the electrical power free synthesis of metal nanoparticles. In order to realize a microreactor capable of on-site synthesis of monodisperse nanoparticles, optimization studies by bulk biosynthesis at varying ratios of the precursor and the reducing agent followed by UV–VIS absorption studies were performed to determine the appropriate mixing ratio. Later, a custom designed microfluidic micromixer was used to perform volumetric flow rate optimizations at the desired ratio using syringe pumps. From the knowledge of the precursor and reducing agent ratio and the flow rates, we modified the hydraulic resistance of micro-mixer inlets by varying the channel geometry to meet the optimized specifications leading to effective synthesis. The synthesized nanoparticles were characterized by UV–VIS spectroscopy, XPS, FTIR, EDS, HRTEM and SAED. The crystal lattice planes of [111] and [220] from the SAED pattern confirms the presence of silver nanoparticles. HRTEM study elucidates that the size of the synthesized nanoparticles is between 2 and 10 nm.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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Current study relates to the development of an electrical power-free, handheld microfluidic nanoparticle synthesizer for synthesis of uniform sized silver nanoparticles at room temperature. The synthesizer module consists of a custom designed microreactor and employs negative pressure based pumping mechanism for the electrical power free synthesis of metal nanoparticles. In order to realize a microreactor capable of on-site synthesis of monodisperse nanoparticles, optimization studies by bulk biosynthesis at varying ratios of the precursor and the reducing agent followed by UV–VIS absorption studies were performed to determine the appropriate mixing ratio. Later, a custom designed microfluidic micromixer was used to perform volumetric flow rate optimizations at the desired ratio using syringe pumps. From the knowledge of the precursor and reducing agent ratio and the flow rates, we modified the hydraulic resistance of micro-mixer inlets by varying the channel geometry to meet the optimized specifications leading to effective synthesis. The synthesized nanoparticles were characterized by UV–VIS spectroscopy, XPS, FTIR, EDS, HRTEM and SAED. The crystal lattice planes of [111] and [220] from the SAED pattern confirms the presence of silver nanoparticles. HRTEM study elucidates that the size of the synthesized nanoparticles is between 2 and 10 nm. |
| 4. | Julius, Lourdes Albina Nirupa; Jagannadh, Veerendra Kalyan; Michael, Issac J; Srinivasan, Rajesh; Gorthi, Sai Siva Design and validation of on-chip planar mixer based on advection and viscoelastic effects Journal Article BioChip Journal, 10 (1), pp. 16-24, 2016. Abstract | BibTeX | Links: @article{Julius2016,
title = {Design and validation of on-chip planar mixer based on advection and viscoelastic effects},
author = {Lourdes Albina Nirupa Julius and Veerendra Kalyan Jagannadh and Issac J. Michael and Rajesh Srinivasan and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/Julius2016_Article_DesignAndValidationOfOn-chipPl.pdf},
doi = {10.1007/s13206-016-0103-1},
year = {2016},
date = {2016-03-31},
journal = {BioChip Journal},
volume = {10},
number = {1},
pages = {16-24},
abstract = {Mixing at low Reynolds number is usually due to diffusion and requires longer channel lengths for complete mixing. In order to reduce the mixing lengths, advective flow can be induced by varying the channel geometry. Additionally, in non-newtonian fluids, appropriate modifications to channel geometry can be used to aid the mixing process by capitalizing on their viscoelastic nature. Here we have exploited the advection and viscoelastic effects to implement a planar passive micro-mixer. Microfluidic devices incorporating different blend of mixing geometries were conceived. The optimum design was chosen based on the results of the numerical simulations performed in COMSOL. The chosen design had sudden expansion and contraction along with teeth patterns along the channel walls to improve mixing. Mixing of two different dyes was performed to validate the mixing efficiency. Particle dispersion experiments were also carried out. The results indicated effective mixing. In addition, the same design was also found to be compatible with electrical power free pumping mechanism like suction. The proposed design was then used to carry out on-chip chemical cell lysis with human whole blood samples to establish its use with non-newtonian fluids. Complete lysis of the erythrocytes was observed leaving behind the white blood cells at the outlet.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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Mixing at low Reynolds number is usually due to diffusion and requires longer channel lengths for complete mixing. In order to reduce the mixing lengths, advective flow can be induced by varying the channel geometry. Additionally, in non-newtonian fluids, appropriate modifications to channel geometry can be used to aid the mixing process by capitalizing on their viscoelastic nature. Here we have exploited the advection and viscoelastic effects to implement a planar passive micro-mixer. Microfluidic devices incorporating different blend of mixing geometries were conceived. The optimum design was chosen based on the results of the numerical simulations performed in COMSOL. The chosen design had sudden expansion and contraction along with teeth patterns along the channel walls to improve mixing. Mixing of two different dyes was performed to validate the mixing efficiency. Particle dispersion experiments were also carried out. The results indicated effective mixing. In addition, the same design was also found to be compatible with electrical power free pumping mechanism like suction. The proposed design was then used to carry out on-chip chemical cell lysis with human whole blood samples to establish its use with non-newtonian fluids. Complete lysis of the erythrocytes was observed leaving behind the white blood cells at the outlet. |
| 5. | Jagannadh, Veerendra Kalyan; Bhat, Bindu Prabhath; Julius, Lourdes Albina Nirupa; Gorthi, Sai Siva High-throughput miniaturized microfluidic microscopy with radially parallelized channel geometry Journal Article Analytical and Bioanalytical Chemistry, 408 (7), pp. 1909-1916, 2016. Abstract | BibTeX | Links: @article{Jagannadh2016,
title = {High-throughput miniaturized microfluidic microscopy with radially parallelized channel geometry},
author = {Veerendra Kalyan Jagannadh and Bindu Prabhath Bhat and Lourdes Albina Nirupa Julius and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/Jagannadh2016_Article_High-throughputMiniaturizedMic.pdf},
doi = {10.1007/s00216-015-9301-2},
year = {2016},
date = {2016-03-31},
journal = {Analytical and Bioanalytical Chemistry},
volume = {408},
number = {7},
pages = {1909-1916},
abstract = {In this article, we present a novel approach to throughput enhancement in miniaturized microfluidic microscopy systems. Using the presented approach, we demonstrate an inexpensive yet high-throughput analytical instrument. Using the high-throughput analytical instrument, we have been able to achieve about 125,880 cells per minute (more than one hundred and twenty five thousand cells per minute), even while employing cost-effective low frame rate cameras (120 fps). The throughput achieved here is a notable progression in the field of diagnostics as it enables rapid quantitative testing and analysis. We demonstrate the applicability of the instrument to point-of-care diagnostics, by performing blood cell counting. We report a comparative analysis between the counts (in cells per μl) obtained from our instrument, with that of a commercially available hematology analyzer.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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In this article, we present a novel approach to throughput enhancement in miniaturized microfluidic microscopy systems. Using the presented approach, we demonstrate an inexpensive yet high-throughput analytical instrument. Using the high-throughput analytical instrument, we have been able to achieve about 125,880 cells per minute (more than one hundred and twenty five thousand cells per minute), even while employing cost-effective low frame rate cameras (120 fps). The throughput achieved here is a notable progression in the field of diagnostics as it enables rapid quantitative testing and analysis. We demonstrate the applicability of the instrument to point-of-care diagnostics, by performing blood cell counting. We report a comparative analysis between the counts (in cells per μl) obtained from our instrument, with that of a commercially available hematology analyzer. |
| 6. | Jagannadh, Veerendra Kalyan; Srinivasan, Rajesh; Gorthi, Sai Siva A semi-automated, field-portable microscopy platform for clinical diagnostic applications Journal Article AIP Advances, 5 (8), 2015. Abstract | BibTeX | Links: @article{Jagannadh2015b,
title = {A semi-automated, field-portable microscopy platform for clinical diagnostic applications},
author = {Veerendra Kalyan Jagannadh and Rajesh Srinivasan and Sai Siva Gorthi},
doi = {10.1063/1.4915133},
year = {2015},
date = {2015-03-24},
journal = {AIP Advances},
volume = {5},
number = {8},
abstract = {Clinical microscopy is a versatile diagnostic platform used for diagnosis of a multitude of diseases. In the recent past, many microfluidics based point-of-care diagnostic devices have been developed, which serve as alternatives to microscopy. However, these point-of-care devices are not as multi-functional and versatile as clinical microscopy. With the use of custom designed optics and microfluidics, we have developed a versatile microscopy-based cellular diagnostic platform, which can be used at the point of care. The microscopy platform presented here is capable of detecting infections of very low parasitemia level (in a very small quantity of sample), without the use of any additional computational hardware. Such a cost-effective and portable diagnostic device, would greatly impact the quality of health care available to people living in rural locations of the world. Apart from clinical diagnostics, it’s applicability to field research in environmental microbiology has also been outlined.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Clinical microscopy is a versatile diagnostic platform used for diagnosis of a multitude of diseases. In the recent past, many microfluidics based point-of-care diagnostic devices have been developed, which serve as alternatives to microscopy. However, these point-of-care devices are not as multi-functional and versatile as clinical microscopy. With the use of custom designed optics and microfluidics, we have developed a versatile microscopy-based cellular diagnostic platform, which can be used at the point of care. The microscopy platform presented here is capable of detecting infections of very low parasitemia level (in a very small quantity of sample), without the use of any additional computational hardware. Such a cost-effective and portable diagnostic device, would greatly impact the quality of health care available to people living in rural locations of the world. Apart from clinical diagnostics, it’s applicability to field research in environmental microbiology has also been outlined. |
| 7. | Jagannadh, Veerendra Kalyan; Adhikari, Jayesh Vasudeva; Gorthi, Sai Siva Automated cell viability assessment using a microfluidics based portable imaging flow analyzer Journal Article AIP Biomicrofluids, 9 (2), 2015. Abstract | BibTeX | Links: @article{Jagannadh2015b,
title = {Automated cell viability assessment using a microfluidics based portable imaging flow analyzer},
author = {Veerendra Kalyan Jagannadh and Jayesh Vasudeva Adhikari and Sai Siva Gorthi},
doi = {10.1063/1.4919402},
year = {2015},
date = {2015-04-28},
journal = {AIP Biomicrofluids},
volume = {9},
number = {2},
abstract = {In this work, we report a system-level integration of portable microscopy and microfluidics for the realization of optofluidic imaging flow analyzer with a throughput of 450 cells/s. With the use of a cellphone augmented with off-the-shelf optical components and custom designed microfluidics, we demonstrate a portable optofluidic imaging flow analyzer. A multiple microfluidic channel geometry was employed to demonstrate the enhancement of throughput in the context of low frame-rate imaging systems. Using the cell-phone based digital imaging flow analyzer, we have imaged yeast cells present in a suspension. By digitally processing the recorded videos of the flow stream on the cellphone, we demonstrated an automated cell viability assessment of the yeast cell population. In addition, we also demonstrate the suitability of the system for blood cell counting.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work, we report a system-level integration of portable microscopy and microfluidics for the realization of optofluidic imaging flow analyzer with a throughput of 450 cells/s. With the use of a cellphone augmented with off-the-shelf optical components and custom designed microfluidics, we demonstrate a portable optofluidic imaging flow analyzer. A multiple microfluidic channel geometry was employed to demonstrate the enhancement of throughput in the context of low frame-rate imaging systems. Using the cell-phone based digital imaging flow analyzer, we have imaged yeast cells present in a suspension. By digitally processing the recorded videos of the flow stream on the cellphone, we demonstrated an automated cell viability assessment of the yeast cell population. In addition, we also demonstrate the suitability of the system for blood cell counting. |
| 8. | Jagannadh, Veerendra Kalyan; Murthy, Rashmi Sreeramachandra; Srinivasan, Rajesh; Gorthi, Sai Siva Automated quantitative cytological analysis using portable microfluidic microscopy Journal Article Journal of Biophotonics, 9 (6), pp. 586-595, 2015. Abstract | BibTeX | Links: @article{Jagannadh2015,
title = {Automated quantitative cytological analysis using portable microfluidic microscopy},
author = {Veerendra Kalyan Jagannadh and Rashmi Sreeramachandra Murthy and Rajesh Srinivasan and Sai Siva Gorthi},
doi = {10.1002/jbio.201500108},
year = {2015},
date = {2015-05-20},
journal = {Journal of Biophotonics},
volume = {9},
number = {6},
pages = {586-595},
abstract = {In this article, a portable microfluidic microscopy based approach for automated cytological investigations is presented. Inexpensive optical and electronic components have been used to construct a simple microfluidic microscopy system. In contrast to the conventional slide-based methods, the presented method employs microfluidics to enable automated sample handling and image acquisition. The approach involves the use of simple in-suspension staining and automated image acquisition to enable quantitative cytological analysis of samples. The applicability of the presented approach to research in cellular biology is shown by performing an automated cell viability assessment on a given population of yeast cells. Further, the relevance of the presented approach to clinical diagnosis and prognosis has been demonstrated by performing detection and differential assessment of malaria infection in a given sample.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this article, a portable microfluidic microscopy based approach for automated cytological investigations is presented. Inexpensive optical and electronic components have been used to construct a simple microfluidic microscopy system. In contrast to the conventional slide-based methods, the presented method employs microfluidics to enable automated sample handling and image acquisition. The approach involves the use of simple in-suspension staining and automated image acquisition to enable quantitative cytological analysis of samples. The applicability of the presented approach to research in cellular biology is shown by performing an automated cell viability assessment on a given population of yeast cells. Further, the relevance of the presented approach to clinical diagnosis and prognosis has been demonstrated by performing detection and differential assessment of malaria infection in a given sample. |
| 9. | Jagannadh, Veerendra Kalyan; Mackenzie, Mark D; Pal, Parama; Kar, Ajoy K; Gorthi, Sai Siva Imaging flow cytometry with femtosecond laser-micromachined glass microfluidic channels Journal Article IEEE Journal of Selected Topics in Quantum Electronics, 21 (4), 2015. Abstract | BibTeX | Links: @article{Jagannadh2015b,
title = {Imaging flow cytometry with femtosecond laser-micromachined glass microfluidic channels},
author = {Veerendra Kalyan Jagannadh and Mark D. Mackenzie and Parama Pal and Ajoy K. Kar and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2017/10/06990492.pdf},
doi = {10.1109/JSTQE.2014.2382978},
year = {2015},
date = {2015-08-31},
journal = {IEEE Journal of Selected Topics in Quantum Electronics},
volume = {21},
number = {4},
abstract = {Microfluidic/optofluidic microscopy is a versatile modality for imaging and analyzing properties of cells/particles while they are in flow. In this paper, we demonstrate the integration of fused silica microfluidics fabricated using femtosecond laser machining into optofluidic imaging systems. By using glass for the sample stage of our microscope, we have exploited its superior optical quality for imaging and bio-compatibility. By integrating these glass microfluidic devices into a custom-built bright field microscope, we have been able to image red blood cells in flow with high-throughputs and good fidelity. In addition, we also demonstrate imaging as well as detection of fluorescent beads with these microfluidic devices.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Microfluidic/optofluidic microscopy is a versatile modality for imaging and analyzing properties of cells/particles while they are in flow. In this paper, we demonstrate the integration of fused silica microfluidics fabricated using femtosecond laser machining into optofluidic imaging systems. By using glass for the sample stage of our microscope, we have exploited its superior optical quality for imaging and bio-compatibility. By integrating these glass microfluidic devices into a custom-built bright field microscope, we have been able to image red blood cells in flow with high-throughputs and good fidelity. In addition, we also demonstrate imaging as well as detection of fluorescent beads with these microfluidic devices. |
| 10. | Jagannadh, Veerendra Kalyan; Mackenzie, Mark D; Pal, Parama; Kar, Ajoy K; Gorthi, Sai Siva Optofluidic microscopy using femtosecond micromachined glass microfluidics Conference Proceedings of the 12th International Conference on Fibre Optics and Photonics, 13.-16.12.14, Kharagpur, 2014. Abstract | BibTeX | Links: @conference{Jagannadh2014,
title = {Optofluidic microscopy using femtosecond micromachined glass microfluidics},
author = {Veerendra Kalyan Jagannadh and Mark D. Mackenzie and Parama Pal and Ajoy K. Kar and Sai Siva Gorthi},
url = {http://www.rbccps.org/wp-content/uploads/2017/10/Photonics-2014-T3A.6.pdf},
doi = {10.1364/PHOTONICS.2014.T3A.6},
year = {2014},
date = {2014-12-16},
booktitle = {Proceedings of the 12th International Conference on Fibre Optics and Photonics, 13.-16.12.14, Kharagpur},
abstract = {Optofluidic microscopy is a versatile modality for imaging and analyzing particles and their properties in flow. In this paper, we demonstrate the applicability of microfluidic devices fabricated using femtosecond laser machining in fused silica for integration into optofluidic imaging systems. In addition, glass, being chemically inert, robust, and inexpensive, is ideal for field-deployable prototypes. By using glass for the sample handling component of our microscope, we are able to exploit its superior optical quality for imaging and biocompatibility. By integrating these glass microfluidic devices into a custom-built bright field microscope, we have been able to analyze red blood cells in flow with good fidelity.},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
Optofluidic microscopy is a versatile modality for imaging and analyzing particles and their properties in flow. In this paper, we demonstrate the applicability of microfluidic devices fabricated using femtosecond laser machining in fused silica for integration into optofluidic imaging systems. In addition, glass, being chemically inert, robust, and inexpensive, is ideal for field-deployable prototypes. By using glass for the sample handling component of our microscope, we are able to exploit its superior optical quality for imaging and biocompatibility. By integrating these glass microfluidic devices into a custom-built bright field microscope, we have been able to analyze red blood cells in flow with good fidelity. |
This project addressed two critical technologies for performing complete blood counts for health diagnostics. The technologies include the rapid mixing of samples and reagents in channels of small dimensions and impedance measurements across these channels to measure and characterize the cells flowing through them. The process workflow is completely automated (liquid injection, mixing and handling processes such as lysing and quenching) and novel approaches have been adopted to fabricate miniature (less than a hundred microns) electrodes in the walls of the channels. This technology is currently being spun-off as a startup (MicroX Labs).
A micro-diffractive structure patterned on a thin film surface enables the differential read-out of phase and amplitude change caused due to the molecular adsorption on the surface with a limit of detection as low as 3×10-6 RIU (refractive index units equivalent to an optical thickness of about 10 picometers) comparable to dominant techniques such as Surface Plasmon Resonance (SPR). This technique also allows the measurement of molecular binding kinetics similar to SPR.
Our implementation was based on transmission mode measurements and therefore enabled the use of low cost CMOS imagers, e.g. mobile phone cameras, to be used for interferometric measurements of molecular adsorption or refractive index changes. Such devices are very beneficial for low cost point-of-care diagnostics among other applications. Interferometry is one of the most sensitive metrological technique available today and is being used to detect gravitational waves (LIGO project), which are one of the weakest phenomena known to mankind.
Implementing interferometry using our micro-fabricated devices attached on top of the camera of a smart phone was the first demonstration of the mobile phone as a sophisticated metrological tool. Our microfabricated device consists of photolithographically patterned glass surface consisting of microarrays of a specified depth designed to maximize the interferometric contrast. Any small refractive index (or thickness) perturbation on this device can be measured as a change in diffraction pattern which is captured by the mobile phone camera. As pointed earlier, this interferometric technique is comparable to existing optical bio-detection techniques such as SPR.
| 1. | Sasikumar, Harish; Varma, Manoj Detection limit for optically sensing specific protein interactions in free-solution Journal Article arXiv: Physics, 2017. Abstract | BibTeX | Links: @article{Sasikumar2017,
title = {Detection limit for optically sensing specific protein interactions in free-solution},
author = {Harish Sasikumar and Manoj Varma},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/1712.00224.pdf},
year = {2017},
date = {2017-12-01},
journal = {arXiv: Physics},
abstract = {Optical molecular sensing techniques are often limited by the refractive index change associated with the probed interactions. In this work, we present a closed form analytical model to estimate the magnitude of optical refractive index change arising from protein-protein interactions. The model, based on the Maxwell Garnett effective medium theory and first order chemical kinetics serves as a general framework for estimating the detection limits of optical sensing of molecular interactions. The model is applicable to situations where one interacting species is immobilized to a surface, as commonly done, or to emerging techniques such as Back-Scattering Interferometry (BSI) where both interacting species are un-tethered. Our findings from this model point to the strong role of as yet unidentified factors in the origin of the BSI signal resulting in significant deviation from linear optical response. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Optical molecular sensing techniques are often limited by the refractive index change associated with the probed interactions. In this work, we present a closed form analytical model to estimate the magnitude of optical refractive index change arising from protein-protein interactions. The model, based on the Maxwell Garnett effective medium theory and first order chemical kinetics serves as a general framework for estimating the detection limits of optical sensing of molecular interactions. The model is applicable to situations where one interacting species is immobilized to a surface, as commonly done, or to emerging techniques such as Back-Scattering Interferometry (BSI) where both interacting species are un-tethered. Our findings from this model point to the strong role of as yet unidentified factors in the origin of the BSI signal resulting in significant deviation from linear optical response. |
| 2. | Sasikumar, Harish; Varma, Manoj Exploiting transient phenomena for imaging with breath figures Journal Article Applied Physics Letters, 110 (7), pp. 071602:1-5, 2017. Abstract | BibTeX | Links: @article{Sasikumar2017b,
title = {Exploiting transient phenomena for imaging with breath figures },
author = {Harish Sasikumar and Manoj Varma},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/1.4976313.pdf},
doi = {10.1063/1.4976313},
year = {2017},
date = {2017-02-13},
journal = {Applied Physics Letters},
volume = {110},
number = {7},
pages = {071602:1-5},
abstract = {Breath figures refer to the patterns formed when vapor condenses into the liquid phase on a surface, revealing heterogeneities in topography or chemical composition. These figures are composed of micro-droplets, which scatter light and produce optical contrast. Differences in hydrophobicity imposed by surface features or contaminants result in a difference in micro-droplet densities, which has been used in applications such as substrate independent optical visualization of single layer graphene flakes. Here, we show that transient phenomena, such as the pinning transition of micro-droplets condensed over a polymer surface, can be used to enhance the optical contrast even when the time averaged difference in micro-droplet densities is not substantial. Thus, this work opens a new way of visualizing surface heterogeneities using transient phenomena occurring during condensation or evaporation of micro-droplets as opposed to only using time averaged differences in wettability due to the surface features.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Breath figures refer to the patterns formed when vapor condenses into the liquid phase on a surface, revealing heterogeneities in topography or chemical composition. These figures are composed of micro-droplets, which scatter light and produce optical contrast. Differences in hydrophobicity imposed by surface features or contaminants result in a difference in micro-droplet densities, which has been used in applications such as substrate independent optical visualization of single layer graphene flakes. Here, we show that transient phenomena, such as the pinning transition of micro-droplets condensed over a polymer surface, can be used to enhance the optical contrast even when the time averaged difference in micro-droplet densities is not substantial. Thus, this work opens a new way of visualizing surface heterogeneities using transient phenomena occurring during condensation or evaporation of micro-droplets as opposed to only using time averaged differences in wettability due to the surface features. |
| 3. | Sasikumar, Harish; Prasad, Vishnu; Pal, Parama; Varma, Manoj Diffractive interference optical analyzer (DiOPTER) Conference Proceedings of the 2016 SPIE International Conference Optical Diagnostics and Sensing XVI: Toward Point-of-Care Diagnostics, 13.02.16, San Francisco (USA), 9715 , 2016. Abstract | BibTeX | Links: @conference{Sasikumar2016,
title = {Diffractive interference optical analyzer (DiOPTER)},
author = {Harish Sasikumar and Vishnu Prasad and Parama Pal and Manoj Varma},
doi = {10.1117/12.2211745},
year = {2016},
date = {2016-02-16},
booktitle = {Proceedings of the 2016 SPIE International Conference Optical Diagnostics and Sensing XVI: Toward Point-of-Care Diagnostics, 13.02.16, San Francisco (USA)},
volume = {9715},
abstract = {This report demonstrates a method for high-resolution refractometric measurements using, what we have termed as, a Diffractive Interference Optical Analyzer (DiOpter). The setup consists of a laser, polarizer, a transparent diffraction grating and Si-photodetectors. The sensor is based on the differential response of diffracted orders to bulk refractive index changes. In these setups, the differential read-out of the diffracted orders suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6x10(-7) RIU was achieved in glass. This work focuses on devices with integrated sample well, made on low-cost PDMS. As the detection methodology is experimentally straightforward, it can be used across a wide array of applications, ranging from detecting changes in surface adsorbates via binding reactions to estimating refractive index (and hence concentration) variations in bulk samples. An exciting prospect of this technique is the potential integration of this device to smartphones using a simple interface based on transmission mode configuration. In a transmission configuration, we were able to achieve an LoD of 4x10(-4) RIU which is sufficient to explore several applications in food quality testing and related fields. We are envisioning the future of this platform as a personal handheld optical analyzer for applications ranging from environmental sensing to healthcare and quality testing of food products.},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
This report demonstrates a method for high-resolution refractometric measurements using, what we have termed as, a Diffractive Interference Optical Analyzer (DiOpter). The setup consists of a laser, polarizer, a transparent diffraction grating and Si-photodetectors. The sensor is based on the differential response of diffracted orders to bulk refractive index changes. In these setups, the differential read-out of the diffracted orders suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6x10(-7) RIU was achieved in glass. This work focuses on devices with integrated sample well, made on low-cost PDMS. As the detection methodology is experimentally straightforward, it can be used across a wide array of applications, ranging from detecting changes in surface adsorbates via binding reactions to estimating refractive index (and hence concentration) variations in bulk samples. An exciting prospect of this technique is the potential integration of this device to smartphones using a simple interface based on transmission mode configuration. In a transmission configuration, we were able to achieve an LoD of 4x10(-4) RIU which is sufficient to explore several applications in food quality testing and related fields. We are envisioning the future of this platform as a personal handheld optical analyzer for applications ranging from environmental sensing to healthcare and quality testing of food products. |
| 4. | Pal, Parama; Sasikumar, Harish; Varma, Manoj Label-free biosensing using diffractive optical analysis Conference Proceedings of the 13th International Conference on Fiber Optics and Photonics, 04.-06.12.16, Kanpur (India), 2016. Abstract | BibTeX | Links: @conference{Pal2016,
title = {Label-free biosensing using diffractive optical analysis},
author = {Parama Pal and Harish Sasikumar and Manoj Varma},
doi = {10.1364/PHOTONICS.2016.Th2F.1},
year = {2016},
date = {2016-12-08},
booktitle = {Proceedings of the 13th International Conference on Fiber Optics and Photonics, 04.-06.12.16, Kanpur (India)},
abstract = {We demonstrate a biosensing technique based on high-resolution (~10-6 refractive index units) refractometric measurements for detecting time-resolved concentration variations in surface (due to the binding of adsorbates) as well as in bulk samples.},
keywords = {},
pubstate = {published},
tppubtype = {conference}
}
We demonstrate a biosensing technique based on high-resolution (~10-6 refractive index units) refractometric measurements for detecting time-resolved concentration variations in surface (due to the binding of adsorbates) as well as in bulk samples. |
| 5. | Kumawat, Nityanand; Pal, Parama; Varma, Manoj Diffractive optical analysis for refractive index sensing using transparent phase gratings Journal Article Nature Scientific Reports, 5 , 2015. Abstract | BibTeX | Links: @article{Kumawat2015,
title = {Diffractive optical analysis for refractive index sensing using transparent phase gratings},
author = {Nityanand Kumawat and Parama Pal and Manoj Varma},
url = {http://www.rbccps.org/wp-content/uploads/2018/12/srep16687.pdf},
doi = {10.1038/srep16687},
year = {2015},
date = {2015-11-18},
journal = {Nature Scientific Reports},
volume = {5},
abstract = {We report the implementation of a micro-patterned, glass-based photonic sensing element that is capable of label-free biosensing. The diffractive optical analyzer is based on the differential response of diffracted orders to bulk as well as surface refractive index changes. The differential read-out suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6 × 10^−7 was achieved with this technique with scope for further improvement.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We report the implementation of a micro-patterned, glass-based photonic sensing element that is capable of label-free biosensing. The diffractive optical analyzer is based on the differential response of diffracted orders to bulk as well as surface refractive index changes. The differential read-out suppresses signal drifts and enables time-resolved determination of refractive index changes in the sample cell. A remarkable feature of this device is that under appropriate conditions, the measurement sensitivity of the sensor can be enhanced by more than two orders of magnitude due to interference between multiply reflected diffracted orders. A noise-equivalent limit of detection (LoD) of 6 × 10^−7 was achieved with this technique with scope for further improvement. |