Optofluidic sensing utilizes the advantages of both microfluidic and optical science to achieve tunable and reconfigurable high-performance sensing purpose, which has established itself as a new and dynamic research field for exciting developments at the interface of photonics, microfluidics, and the life sciences. With the trend of developing miniaturized electronic devices and integrating multi-functional units on lab-on-a-chip instruments, more and more desires request for novel and powerful approaches to integrating optical elements and fluids on the same chip-scale system in recent years. By taking advantage of the electrowetting phenomenon, the wettability of liquid droplet on micro/nano-structured surfaces and the Leidenfrost effect, this doctoral research focuses on developing high-performance optofluidic sensing systems, including optical beam adaptive steering, whispering gallery mode (WGM) optical sensing, and surface-enhanced Raman spectroscopy (SERS) sensing. A watermill-like beam steering system is developed that can adaptively guide concentrating optical beam to targeted receivers. The system comprises a liquid droplet actuation mechanism based on electrowetting-on-dielectric, a superlattice-structured rotation hub, and an enhanced optical reflecting membrane. The specular reflector can be adaptively tuned within the lateral orientation of 360°, and the steering speed can reach ~353.5°/s. This work demonstrates the feasibility of driving a macro-size solid structure with liquid microdroplets, opening a new avenue for developing reconfigurable components such as optical switches in next-generation sensor network. Furthermore, the WGM sensing system is demonstrated to be stimulated along the meridian plane of a liquid microdroplet, instead of equatorial plane, resting on a properly designed nanostructured chip surface. The unavoidable deformation along the meridian rim of the sessile microdroplet can be controlled and regulated by tailoring the nanopillar structures and their associated hydrophobicity. The nanostructured superhydrophobic chip surface and its impact on the microdroplet morphology are modeled by Surface Evolver (SE), which is subsequently validated by the Cassie-Wenzel theory of wetting. The influence of the microdroplet morphology on the optical characteristics of WGMs is further numerically studied using the Finite-Difference Time-Domain method (FDTD) and it is found that meridian WGMs with intrinsic quality factor Q exceeding 104 can exist. Importantly, such meridian WGMs can be efficiently excited by a waveguiding structure embedded in the planar chip, which could significantly reduce the overall system complexity by eliminating conventional mechanical coupling parts. Our simulation results also demonstrate that this optofluidic resonator can achieve a sensitivity as high as 530 nm/RIU. This on-chip coupling scheme could pave the way for developing lab-on-a-chip resonators for high-resolution sensing of trace analytes in various applications ranging from chemical detections, biological reaction processes to environmental protection. Lastly, this research reports a new type of high-performance SERS substrate with nanolaminated plasmonic nanostructures patterned on a hierarchical micro/nanostructured surface, which demonstrates SERS enhancement factor as high as 1.8 x 107. Different from the current SERS substrates which heavily relies on durability-poor surface structure modifications and various chemical coatings on the platform surfaces which can deteriorate the SERS enhancement factor (EF) as the coating materials may block hot spots, the Leidenfrost effect-inspired evaporation approach is proposed to minimize the analyte deposition area and maximize the analyte concentration on the SERS sensing substrate. By intentionally regulating the temperature of the SERS substrate during evaporation process, the Rhodamine 6G (R6G) molecules inside a droplet with an initial concentration of 10-9 M is deposited within an area of 450 μm2, and can be successfully detected with a practical detection time of 0.1 s and a low excitation power of 1.3 mW. / Doctor of Philosophy / Over the past two decades, optofluidics has emerged and established itself as a new and exciting research field for novel sensing technique development at the intersection of photonics, microfluidics and the life sciences. The strong desire for developing miniaturized lab-on-a-chip devices and instruments has led to novel and powerful approaches to integrating optical elements and fluids on the same chip-scale systems. By taking advantage of the electrowetting phenomenon, the wettability of liquid droplet on micro/nano-structured surfaces and the Leidenfrost effect, this doctoral program focuses on developing high-performance optofluidic sensing systems, including optical beam adaptive steering, whispering gallery mode (WGM) optical sensing, and surface-enhanced Raman spectroscopy (SERS) sensing. During this doctoral program, a rotary electrowetting-on-dielectric (EWOD) beam steering system was first fabricated and developed with a wide lateral steering range of 360° and a fast steering speed of 353.5°/s, which can be applied in telecommunication systems or lidar systems. Next, the meridian WGM optical sensing system was optically simulated using finite difference time domain (FDTD) method and was numerically validated to achieve a high quality-factor Q exceeding 104 and a high refractive index sensitivity of 530 nm/RIU, which can be applied to the broad areas of liquid identification or single molecule detection. Lastly, a SERS sensing platform based on a hierarchical micro/nano-structured surface was accomplished to exhibit a decent SERS enhancement factor (EF) of 1.81 x 107. The contact angle of water droplet on the SERS substrate is 134° with contact angle hysteresis of ~32°. Therefore, by carefully controlling the SERS surface temperature, we employed Leidenfrost evaporation to concentrate the analytes within an extremely small region, enabling the high-resolution detection of analytes with an ultra-low concentration of ~10-9 M.

No / A method for measuring the evaporation kinetics of pure solvents and solutions containing Cd3P2 quantum dots (QDs) in SiO/SiO2 rolled-up microtube (RUT) resonators is reported. The QDs serve as wavelength-tunable fluorescent sources for the RUT resonator. The first-order kinetic constant (295 K) of the evaporation of toluene embedded in a RUT (D = 9.10 μm) is evaluated (0.055 min−1). / Doctoral Program Education of China. Grant Number: 20110111120008; Alexander von Humboldt Foundation

Biological research and Clinical Diagnostics heavily rely on Optical Microscopy for analyzing properties of cells. The experimental protocol for con-ducting a microscopy based diagnostic test consists of several manual steps, like sample extraction, slide preparation and inspection. Recent advances in optical microscopy have predominantly focused on resolution enhancement. Whereas, the aspect of automating the manual steps and enhancing imaging throughput were relatively less explored. Cost-e ective automation of clinical microscopy would potentially enable the creation of diagnostic devices with a wide range of medical and biological applications. Further, automation plays an important role in enabling diagnostic testing in resource-limited settings. This thesis presents a novel optofluidics based approach for automation of clinical diagnostic microscopy. A system-level integrated optofluidic architecture, which enables the automation of overall diagnostic work- ow has been proposed. Based on the proposed architecture, three different prototypes, which can enable point-of-care (POC) imaging cytometry have been developed. The characterization of these prototypes has been performed. Following which, the applicability of the platform for usage in diagnostic testing has been validated. The prototypes were used to demonstrate applications like Cell Viability Assay, Red Blood Cell Counting, Diagnosis of Malaria and Spherocytosis. An important performance metric of the device is the throughput (number of cells imaged per second). A novel microfluidic channel design, capable of enabling imaging throughputs of about 2000 cells per second has been incorporated into the instrument. Further, material properties of the sample handling component (microfluidic device) determine several functional aspects of the instrument. Ultrafast-laser inscription (ULI) based glass microfluidic devices have been identi ed and tested as viable alternatives to Polydimethylsiloxane (PDMS) based microfluidic chips. Cellular imaging with POC platforms has thus far been limited to acquisition of 2D morphology. To potentially enable 3D cellular imaging with POC platforms, a novel slanted channel microfluidic chip design has been proposed. The proposed design has been experimentally validated by performing 3D imaging of fluorescent microspheres and cells. It is envisaged that the proposed innovation would aid to the current e orts towards implementing good quality health-care in rural scenarios. The thesis is organized in the following manner : The overall thesis can be divided into two parts. The first part (chapters 2, 3) of the thesis deals with the optical aspects of the proposed Optofluidic instrument (development, characterization and validations demonstrating its use in poc diagnostic applications). The second part (chapters 4,5,6) of the thesis details the microfluidic sample handling aspects implemented with the help of custom fabricated microfludic devices, the integration of the prototype, func-tional framework of the device. Chapter 2 introduces the proposed optofluidic architecture for implementing the POC tool. Further, it details the first implementation of the proposed platform, based on the philosophy of adapting ubiquitously available electronic imaging devices to perform cellular diagnostic testing. The characterization of the developed prototypes is also detailed. Chapter 3 details the development of a stand-alone prototype based on the proposed architecture using inexpensive o -the-shelf, low frame-rate image sensors. The characterization of the developed prototype and its performance evaluation for application in malaria diagnostic testing are also presented. The chapter concludes with a comparative evaluation of the developed prototypes, so far. Chapter 4 presents a novel microfludic channel design, which enables the enhancement of imaging throughput, even while employing an inexpensive low frame-rate imaging modules. The design takes advantage of radial arrangement of microfludic channels for enhancing the achievable imaging throughput. The fabrication of the device and characterization of achievable throughputs is presented. The stand-alone optofluidic imaging system was then integrated into a single functional unit, with the proposed microfluidic channel design, a viscoelastic effect based micro uidic mixer and a suction-based microfluidic pumping mechanism. Chapter 5 brings into picture the aspect of the material used to fabricate the sample handling unit, the robustness of which determines certain functional aspects of the device. An investigative study on the applicability of glass microfluidic devices, fabricated using ultra-fast laser inscription in the context of the microfluidics based imaging flow cytometry is presented. As detailed in the introduction, imaging in poc platforms, has thus far been limited to acquisition of 2D images. The design and implementation of a novel slanted channel microfluidic chip, which can potentially enable 3D imaging with simplistic optical imaging systems (such as the one reported in the earlier chapters of this thesis) is detailed. A example application of the proposed microfludic chip architecture for imaging 3D fluorescence imaging of cells in flow is presented. Chapter 6 introduces a diagnostic assessment framework for the use of the developed of m in an actual clinical diagnostic scenario. The chapter presents the use of computational signatures (extracted from cell images) to be employed for cell recognition, as part of the proposed framework. The experimental results obtained while employing the framework to identify cells from three different leukemia cell lines have been presented in this chapter. Chapter 7 summarizes the contributions reported in this thesis. Potential future scope of the work is also detailed.

La détection d'espèces (bio)chimiques à de très faibles concentrations représente un enjeu croissant dans les domaines de la santé, de l’environnement et de la défense. Un microrésonateur optique en polymère, sans marqueurs fluorescents, associé à un canal microfluidique, forme un capteur optofluidique, ce qui permet la détection d'analytes par interaction entre un champ évanescent à la surface du microrésonateur et la solution contenant l’espèce à étudier. Cette thèse présente la conception et la réalisation de capteurs optofluidiques à base de microrésonateurs optiques et de circuits microfluidiques en polymères, pour une très faible limite de détection et un temps de réponse rapide. De très bons résultats ont été obtenus en termes de limite de détection de polluants de type ions lourds dans l'eau, en abordant le problème sous différents angles : conception et réalisation de circuits optiques et microfluidiques, optimisation de l’interrogation optique du capteur par l’élaboration d’une méthodologie de mesure rapide et précise et un traitement du signal adéquat, étude des propriétés physico-chimiques des surfaces polymères, mise au point d’une instrumentation adaptée. Le capteur a permis la détection d'ions cadmium, ions hautement toxiques, jusqu'à une décision limite de détection de 50 pmol/L dans l'eau déionisée et 500 pmol/L dans l'eau du robinet grâce à un greffage sur la surface du microrésonateur de 2,2’- ((4-Amino-1,2-Phénylène) Bis (Carboxylatoazanédyil)) Diacétate. Une étude de régénération de la surface fonctionnalisée des microrésonateurs pour la détection d’ions cadmium a été réalisée et ce capteur a pu être régénéré pour plus de soixante mesures consécutives. D’autre part, l'analyse simultanée de deux polarisations orthogonales entre elles TE et TM de la réponse optique du capteur permet d’optimiser la sensibilité de mesure. Une étude de mesure différentielle consistant à comparer simultanément les mesures sur deux microrésonateurs identiques placés dans les même conditions physiques, l’un jouant le rôle de référence et l’autre étant un capteur spécifique, a permis de s’affranchir des différentes perturbations externes (pression, température, attachements non spécifiques). Ces instruments « multi-capteurs » sont également essentiels pour une compréhension détaillée des mécanismes de réactions de surface, une évaluation de l'efficacité d'accrochage de différents protocoles de fonctionnalisation et des mesures en multiplexage. / High sensitivity biochemical sensing is a concern for health, environment and defense. Thanks to the interaction between an analyte and an evanescent field at their surface, label-free polymer microring resonators, in association with a microfluidic channel, form an optofluidic sensor that can be used for biosensing. This thesis shows the realization of versatile optofluidic sensors based on polymer microring resonators combining a high detection limit with a short response time. High limit of detection of heavy ions in tap water was obtained after a careful optimization of the optical and microfluidic designs, signal processing, methodology of detection, surface chemistry and instrumentation. By functionalizing the resonator surface with 2,2’-((4Amino-1,2- Phenylene)Bis(Carboxylatoazanedyil))Diacetate, we obtained a limit of detection of 50 pmol/L in deionized water and 500 pmol/L in tap water. It should be stressed that the functionalized surface of the resonator was regenerated more than 60 times, enabling several sensing experiments with the same resonator. Besides, we were able to optimize the measurement sensitivity by an analysis of the orthogonal polarizations TE and TM from the sensor optical response. The simultaneous use of at least two microresonators in parallel (providing a reference signal and allowing multiplexing) enabled us to improve measurement accuracy and to compensate the signal from various external perturbations such as pressure, temperature and non-specific bindings. These “multi-sensors” are essential for (i) an in-depth understanding of surface reaction mechanism, (ii) an evaluation of the binding efficiency of different functionalization protocols and (iii) a high throughput characterization tool for multiple detections of pollutants.

No description available.

[pt] Cristais líquidos são amplamente utilizados atualmente em telas e filtros. Contudo, o alinhamento dos cristais líquidos possui uma resposta relativamente lenta (da ordem de milissegundos) devido à necessidade da interação entre vizinhos próximos. Em contrapartida, nanobastões de ouro são capazes de alinhar-se a um campo elétrico, mesmo quando isolados, devido à sua susceptibilidade elétrica elevada comparada a dos cristais líquidos, apresentando uma resposta de alinhamento significativamente mais rápida que a dos cristais líquidos. A forma alongada dos nanobastões faz com que sua absorção e seu espalhamento de luz, ocasionados pelo efeito de Ressonância de Plasmon de Superfície Localizado (Localized Surface Plasmon Resonance – LSPR), sejam altamente dependentes da orientação relativa dos nanobastões à polarização da luz incidente. Por isso, suspensões de nanobastões têm se tornado um novo paradigma em controle de luz por alinhamento induzido por campo elétrico. Neste trabalho, é apresentado um estudo da dinâmica de alinhamento dos nanobastões, por meio de medidas de transmissão de luz por um componente que permite a interação da luz com a suspensão de nanobastões enquanto sob influência de um campo elétrico de alinhamento. Foi encontrado um tempo de resposta de 1,5 microssegundos, 3 ordens de grandeza mais rápido que o de cristais líquidos comuns. Um segundo experimento foi realizado com um componente com dois pares de eletrodos transversais, no qual foi possível eliminar a relaxação lenta do sistema, demonstrando assim um chaveamento óptico digital com tempo de resposta da ordem de 110 Newton vezes segundo. Dois modelos teóricos foram propostos para descrever a dinâmica de alinhamento dos nanobastões e foi demonstrado que ambos os modelos ajustam bem os dados experimentais. Apresentamos também uma relação de equivalência entre os dois modelos. / [en] Liquid crystals are widely used nowadays in displays and optical filters. However, the alignment of liquid crystals has a relatively slow switching response (of the order of milliseconds) due to the near-neighbor interaction. In contrast, the high electrical susceptibility of a single gold nanorod enables its alignment to an external electric field, presenting a significantly faster switching response than that of liquid crystals. The elongated form of the nanorods makes their absorption and scattering, caused by the Localized Surface Plasmon Resonance (LSPR) effect, to be highly dependent on their orientation relative to the light polarization. Therefore, gold nanorod suspensions have become a new paradigm in light control by electric field-induced alignment. In this work, a study of the alignment dynamics of nanorods is presented, by means of light transmission measurements by a component that allows the interaction of light with the suspension of nanorods while under the influence of an electric field of alignment. An alignment time of 1.5 microseconds was found, which is 3 orders of magnitude smaller than traditional liquid crystal alignment mechanism response time. A second experiment was carried out with a component with two pairs of transverse electrodes, in which it was possible to eliminate the slow relaxation of the system, thus demonstrating a digital optical switch with response of the order of 110 Newton second. Two theoretical models were proposed to describe the alignment dynamics of the nanorods and it was demonstrated that both models fit well the experimental data. An equivalence relation between the two models is presented.

Following the intensive development of isolated (i.e., not coupled with on-chip waveguide) vertically rolled-up microtube ring resonators (VRU-MRRs) for both active and passive applications, a variety of microtube-based devices has been realized. These include microcavity lasers, optical sensors, directional couplers, and active elements in lab-on-a-chip devices. To provide more advanced and complex functionality, the focus of tubular geometry research is now shifting toward (i) refined vertical light transfer in 3D stacks of multiple photonic layers and (ii) to make microfluidic cooling system in the integrated optoelectronic system. Based on this motivation, this PhD research is devoted to the demonstration and the implementation of monolithic integration of VRU-MRRs with photonic waveguides for 3D photonic integration and their optofluidic applications. Prior to integration, high-quality isolated VRU-MRRs on the flat Si substrate are firstly fabricated by the controlled release of differentially strained titanium-dioxide (TiO2) bilayered nanomembranes. The fabricated microtubes support resonance modes for both telecom and visible photonics. The outcome of the isolated VRU-MRRs is a record high Q (≈3.8×10^3) in the telecom wavelength range with optimum tapered optical fiber resonator interaction. To further study the optical modes in the visible and near infrared spectral range, μPL spectroscopy is performed on the isolated VRU-MRRs, which are activated by entrapping various sizes of luminescent nanoparticles (NPs) within the windings of rolled-up nanomembranes based on a flexible, robust and economical method. Moreover, it is realized for the first time, in addition to serving as light sources that NPs-aggregated in isolated VRU-MRRs can produce an optical potential well that can be used to trap optical resonant modes. After achieving all the required parameters for creating a high-quality TiO2 VRU-MRR, the monolithic integration of VRU-MRRs with Si nanophotonic waveguides is experimentally demonstrated, exhibiting a significant step toward 3D photonic integration. The on-chip integration is realized by rolling up 2D pre-strained TiO2 nanomembranes into 3D VRU-MRRs on a microchip which seamlessly expanded over several integrated waveguides. In this intriguing vertical transmission configuration, resonant filtering of optical signals at telecom wavelengths is demonstrated based on ultra-smooth and subwavelength thick-walled VRU-MRRs. Finally, to illustrate the usefulness of the fully integrated VRU-MRRs with photonic waveguides, optofluidic functionalities of the integrated system is investigated. In this work, two methods are performed to explore optofluidic applications of the integrated system. First, the hollow core of an integrated VRU-MRR is uniquely filled with a liquid solution (purified water) by setting one end of the VRU-MRRs in contact with a droplet placed onto the photonic chip via a glass capillary. Second, the outside of an integrated VRU-MRR is fully covered with a big droplet of liquid. Both techniques lead to a significant shift in the WGMs (Δλ≈46 nm). A maximum sensitivity of 140 nm/refractive index unit, is achieved. The achievements of this PhD research open up fascinating opportunities for the realization of massively parallel optofluidic microsystems with more functionality and flexibility for analysis of biomaterials in lab-on-a-tube systems on single chips. It also demonstrates 3D photonic integration in which optical interconnects between multiple photonic layers are required.

Die vorliegende Forschungsarbeit widmet sich der Entwicklung und Untersuchung neuartiger photonischer Kristallstrukuren für Anwendungen in den Gebieten der Nanophotonik und Optofluidik. Dabei konzentriert sich eine erste Serie von Experimenten auf die Charakterisierung und Optimierung photonischer Kristallresonatoren im sichtbaren Spektralbereich, wobei bisher unerreichte Resonatorgüten von bis zu 3400 gezeigt werden können. Diese Strukturen werden anschließend als Plattformen zur Herstellung von hybriden nanophotonischen Bauelementen verwendet, indem externe Partikel (wie z.B. Diamant-Nanokristalle und Metall-Nanopartikel) in kontrollierter Art und Weise an die Resonatoren gekoppelt werden. Zu diesem Zweck wird eine Nanomanipulationsmethode entwickelt, welche Rastersonden zur gezielten Positionierung und Anordnung von Partikeln auf den photonischen Kristallstrukturen benutzt. Verschiedene Arten solcher Hybridelemente werden realisiert und untersucht, einschließlich diamant-gekoppelter Resonatoren, plasmon-gekoppelter Resonatoren und Metall-Diamant Hybridstrukturen. Außer für Anwendungen auf dem Gebiet der Nanophotonik werden verschiedene photonische Kristallstrukturen auch hinsichtlich ihres Leistungsvermögens als biochemische Sensorelemente erforscht. Zum ersten Mal wird eine umfassende numerische Analyse der optischen Kräfte auf Objekte im Nahfeld photonischer Kristallresonatoren durchgeführt, welche neue Möglichkeiten zum Einfang sowie zur Detektion und Untersuchung biologischer Partikel in integrierten optofluidischen Bauteilen bieten. Weiterhin werden unterschiedliche photonische Kristallfasern bezüglich ihrer Detektionssensitivität in Absorptions- und Fluoreszenzmessungen untersucht, wobei sich eine klare Überlegenheit von selektiv befüllten Hohlkern-Designs im Vergleich zu Festkern-Fasern offenbart. / This thesis deals with the development and investigation of novel photonic crystal structures for applications in nanophotonics and optofluidics. Thereby, a first series of experiments focuses on the characterization and optimization of photonic crystal cavities in the visible wavelength range, demonstrating unprecedented cavity quality factors of up to 3400. These structures are subsequently employed as platforms for the creation of advanced hybrid nanophotonic elements by coupling external particles (such as diamond nanocrystals and metal nanoparticles) to the cavities in a well-controlled manner. For this purpose, a nanomanipulation method is developed, utilizing scanning probes for the deterministic positioning and assembly of particles on the photonic crystal structures. Various types of such hybrid elements are realized and investigated, including diamond-coupled cavities, plasmon-coupled cavities, and metal-diamond hybrid structures. Apart from applications in nanophotonics, different types of photonic crystal structures are also studied with regard to their performance as biochemical sensing elements. For the first time a thorough numerical analysis of the optical forces exerted on objects in the near-field of photonic crystal cavities is conducted, providing novel means to trap, detect, and investigate biological particles in integrated optofluidic devices. Furthermore, various types of photonic crystal fibers are studied with regard to their detection sensitivity in absorption and fluorescence measurements, revealing a clear superiority of selectively infiltrated hollow-core designs in comparison to solid-core fibers.

The rapid development of optofluidics, the combination of microfluidics and integrated optics, since its formal conception in the early 2000's has aided in the advance of single-molecule analysis. The optofluidic platform discussed in this dissertation is called the liquid core anti-resonant reflecting optical waveguide (LC-ARROW). This platform uses ARROW waveguides to orthogonally intersect a liquid core waveguide with solid core rib waveguides for the excitation of specifically labeled molecules and collection of fluorescence signal. Since conception, the LC-ARROW platform has demonstrated its effectiveness as a lab-on-a-chip fluorescence biosensor. However, until the addition of optical multiplexing excitation waveguides, the platform lacked a critical functionality for use in rapid disease diagnostics, namely the ability to simultaneously detect different types of molecules and particles. In disease diagnostics, the ability to multiplex, detect and identify multiple biomarkers simultaneously is paramount for a sensor to be used as a rapid diagnostic system. This work brings optofluidic multiplexing to the sensor through the implementation of three specific designs: (1) the Y-splitter was the first multi-spot excitation design implemented on the platform, although it did not have the ability to multiplex it served as a critical stepping stone and showed that multi-spot excitation could improve the signal-to-noise ratio of the platform by ~50,000 times; (2) a multimode interference (MMI) waveguide which took the multi-spot idea and then demonstrated spectral multiplexing capable of correctly identifying multiple diverse biomarkers simultaneously; and, (3) a Triple-Core design which incorporates excitation and collection along multiple liquid cores, enabling spatial multiplexing which increases the number of individual molecules to be identified concurrently with the MMI waveguide excitation. In addition to describing the development of optical multiplexing, this dissertation includes an investigation of another LC-ARROW based design that enables 2D bioparticle trapping, the Anti-Brownian Electrokinetic (ABEL) trap. This design demonstrates two-dimensional compensation of a particle's Brownian motion in solution. The capability to maintain a molecule suspended in solution over time enables the ability to gain a deeper understanding of cellular function and therapies based on molecular functions.

Medical devices are used widely at every stage of disease diagnosis and treatment. To eradicate certain infectious diseases, the development of highly sensitive diagnostic tools and techniques is essential. The work reported in this thesis presents a novel approach, which can be used for the diagnosis of various diseases in the field of clinical cytology. The central theme of this approach was to develop a simple, holistic and completely automated system for point-of-care (POC) diagnostics. This is realized through the Development of an Absorption Flow-Cytometer with Synergistic Integration of Microfluidic, Optics and simple Electronics. Quantitative diagnosis of malaria has been taken as test case for the characterization and validation of the developed technology. Malaria is a life-threatening disease widely prevalent in developing countries. Approximately half the world population undergoes a test of malaria and it kills close to half a million people every year. Early detection and treatment will reduce the number of fatalities and also decrease its transmission rate. In the recent past, several diagnostic tools have been developed to detect malaria but there are varied demands on diagnostic instruments in healthcare settings and endemic contexts. The objective of this thesis is to develop an instrument capable of identifying malaria-infected red blood cells (i-RBCs) from a given few micro-liters of whole blood. The optical absorption properties of blood cells were measured at a single-cell level to diagnose malaria. The proof-of-concept for the instrument was established in four stages, after which a prototype was also developed and validated. In the first stage, a system capable of simultaneously imaging cells and also measuring their optical absorbance properties was developed. The developed system was employed to characterize absorption properties of red blood cells (malaria-infected and healthy ones) on blood-smear. A custom-made bright-field transmission microscope in combination with a pair of laser diode and photo-detector was used to simultaneously image and measure transmittance of infected and uninfected RBCs. In the second stage, the technique was extended to enable high-throughput measurements with the use of microfluidic sample handling and synchronous data acquisition. Using this technique, the optical absorbance and morphology of infected and healthy RBCs have been characterized in statistically significant numbers. The correlation between cell morphology (from images) and single-cell optical absorbance level helped to establish the thresholds for differentiating healthy and infected cells. In the third stage, a portable prototype capable of assessing optical absorbance levels of single cells was fabricated. The developed prototype is capable of assessing cells at throughputs of about 1800 cells/ second. It was initially validated with sample suspensions containing infected and healthy RBCs obtained from malaria cultures. For the device to be usable at the field-level, it has to function in the presence of all other cellular components of whole blood. The optical absorbance of other cellular components of blood like white blood cells and platelets, were characterized. The device was finally tested with blood samples spiked with malaria-infected RBCs validating the overall proof-of-concept and the developed prototype. The deployment of such cost-effective, automated POC system would enable malaria diagnosis at remote locations and play a crucial role in the ongoing efforts to eradicate malaria. In future, the presented technology can be extended to develop POC diagnostic tool for other diseases as well. As it enables quantitative estimation of malaria, the present optical absorption flow analyzer would also find application in disease prognosis monitoring, anti-malarial drug development and other studies requiring measurements on a single-cell basis. The hyper-imaging system can be used to characterize and validate the threshold information, and can be incorporated in the prototype. Thus, it is a continuous process to characterization and implementation in the prototype. The optofluidic absorption flow analyzer will help enable affordable clinical diagnostic testing in resource limited settings. This approach will be extended to diagnose other diseases, using differences in optical absorption as criteria for differentiating healthy and infected cells.