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dc.contributor.advisorGorthi, Sai Siva
dc.contributor.authorKatare, Prateek
dc.date.accessioned2022-09-08T04:25:59Z
dc.date.available2022-09-08T04:25:59Z
dc.date.submitted2022
dc.identifier.urihttps://etd.iisc.ac.in/handle/2005/5848
dc.description.abstractThe role of medical diagnostics is morphing rapidly in the face of imminent challenges such as pandemic preparedness. Correspondingly, in-vitro diagnostics are evolving — growing beyond the traditional Centralized Diagnostic Laboratories (CDL) and now include Point-of-Care Diagnostic (PoCD) devices and lab-on-wheel setups (such as medical diagnostic bus/van) as well. However, even now, the triple challenge of simultaneously meeting Accessibility, Accuracy and Affordability (A3) still remains unaddressed by and large. This implies that all the current diagnostic paradigms either do not provide a sufficiently large range of assays (lack of accessibility), or do so at the expense of accuracy and/or affordability. Unfortunately, there exist several scenarios where meeting this A3 criteria is critical to delivering medical diagnostics. This thesis proposes and builds upon a diagnostic paradigm that has the potential to address this A3 challenge. It highlights how the current, diffused efforts towards miniaturizing CDL or merely building more PoCD devices would not serve the purpose. This is because (a) existing diagnostic instruments cannot be miniaturized sufficiently to be easily transported to points of need, and (b) the underlying technologies of existing instruments are fundamentally different and mutually incompatible, such that their operations and consumables cannot be integrated into one unit. This thesis proposes that research and development efforts should instead be re-oriented towards building a modular, portable diagnostic platform complemented by assay-specific, disposable, “smart” consumables. The platform would contain an integrated set of novel/innovative instrumentation that can carry out all basic unit operations needed for in-vitro diagnostic assays. The platform’s capabilities would be complemented by the “smart” design/processing elements available on the consumables, which provide the remaining needs for conducting the assay. This framework of segregated functionality ensures a compact and low-cost platform as the demands imposed on it are kept minimal. This framework also assures future readiness since the consumable can be continuously re-engineered for improved performance as well as handling any new diagnostic assay as and when needed. The combination of the diagnostic platform and smart consumables is termed here as Lab to Point-of-Need Technology (LPoNT). Such technology needs novel/innovative methods for sample preparation, bio-analyte processing, read-out, reagent storage and fluid handling to transcend the barriers imposed by the existing diagnostic methods. Emerging technologies such as microfluidics and image processing are instrumental to such developments. This thesis presents an opto-fluidic LPoNT platform designed along these lines, and the instrument is demonstrated to perform microscopy imaging as well as optical absorption based measurements, in a semi-automated manner. The platform can switch between the two modalities in a few seconds, allowing a single sample to undergo any of the thousands of tests pertaining to these modalities (Cytology and Biochemical assays). This would otherwise need two different instruments and also different associated consumables as well as operator training. The microscopy unit achieves a resolution of 0.78 µm and the optical absorption unit can acquire broadband (300-800 nm) measurements with a high sensitivity photosensor. The developed platform is low-cost, portable enough to be carried in a backpack, and is modular, extendable. It uses off-the-shelf optical, mechanical and electronic components integrated in a manner that provides a single user-interface (physical and digital) to all functionality. Three methods have been devised to fabricate “smart”, low-cost, disposable consumables that support the utility of the developed platform. The first method demonstrates rapid construction of a low-cost, optically clear cartridge with a fixed volume cavity. This “smart slide” can be used for both, volumetric microscopy as well as optical absorption based measurements. The second method demonstrates “smart curing” of the polymer polydimethylsiloxane (PDMS) and reduces curing time from hours to as low as 2 minutes, without any additional chemical or physical treatment. It is targeted at soft lithography performed with a silicon master mould, and uses a commonly available microwave oven for curing. The method could assist commercial-scale fabrication of PDMS based in-vitro diagnostic devices, many of which are reported in research and are amenable to be used as LPoNT-compatible consumables. The third method demonstrates single-shot, cleanroom-free “smart fabrication” of electrodes and microfluidic channel in low-cost commodity copper coated boards. The “smart” processing element of micro-electrodes would allow operations such as cell counting and membrane lysis, which form essential sub-steps of some assays. Electrodes spaced as close as 50 µm and microchannels as narrow as 240 µm have been constructed. This method lowers the cost barrier to usage of electric-field based bio-manipulation methods in LPoNT consumables. Experiments were conducted with the developed LPoNT platform using clinical whole blood samples, pre-prepared dried smear slides and synthetic solutions of bio-chemical analytes. Experimental results report precise measurement of blood Hemoglobin and Creatinine concentration, and generation of clinically-usable microscopy images of cells. Hemoglobin in clinical samples has been measured with an average error of 2%, which is well below the acceptable limit of 7%. These results pave the way for a large set of assays, including complete blood cell count (CBC) and screening for hemoglobinopathies such as Thalassemia.en_US
dc.language.isoen_USen_US
dc.rightsI grant Indian Institute of Science the right to archive and to make available my thesis or dissertation in whole or in part in all forms of media, now hereafter known. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertationen_US
dc.subjectin vitroen_US
dc.subjectpoint of needen_US
dc.subjectpoint of careen_US
dc.subjectmedical diagnosticsen_US
dc.subject.classificationMedical Diagnosticsen_US
dc.titleLab to Point-of-Need Technology: Solving the A3 puzzle of in-vitro diagnosticsen_US
dc.typeThesisen_US
dc.degree.namePhDen_US
dc.degree.levelDoctoralen_US
dc.degree.grantorIndian Institute of Scienceen_US
dc.degree.disciplineEngineeringen_US


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