Development of a Photothermal Induced Optical Scattering Modulation Technique and Its Application in Malaria Diagnosis
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Date
2023-08
Authors
Memeu, Daniel Maitethia
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
Abstract
Malaria is one of the leading causes of mortality and mobility in Africa and the disease is endemic in many regions of the continent. Though curable, early diagnosis which is key to effective treatment is usually a challenge owing to lack of accurate, rapid and affordable diagnostic techniques in resource scarce settings. Therefore, there exists a need for development of an accurate, rapid, easy to operate and affordable technique for diagnosis of malaria. This work describes a novel optical based sensing and imaging technique termed as Photo-Thermal Induced Optical Scattering Modulation (PTIOSM) and its application in malaria diagnosis. The technique entails sample irradiation with two optical beams of different wavelength. One optical beam, referred to as pump beam is employed for exciting the sample chromophores to higher energy levels. What follows is chromophore transition from the excited states to lower states and subsequent photothermal processes such as photoacoustics and thermal lens effect. These processes are monitored using a second optical beam referred as probe beam. We hypothesized that application of the pump beam alters the sample optical properties and these changes can be monitored by tracking intensity modulation of the probe beam induced by the sample upon optical excitation and relaxation. The extent of the probe beam intensity modulation (referred to as PTIOSM signal) would be indicative of the molecular species present in the sample. We applied the technique for label-free detection of the presence of hemozoin (an endogenous malaria biomarker) in blood samples.Four PTIOSM setups; two for sensing and the other two for imaging were developed. The PTIOSM sensing setup employed a photodiode as the optical detector while the PTIOSM imaging setup used an image sensor for spatial-temporal PTIOSM signal from the sample. Malaria infected and non-infected blood samples as well as whole blood mixed with synthetic hemozoin at different concentrations were interrogated using the PTIOSM setups. The synthetic hemozoin was mixed with whole blood in varying concentrations to simulate different Plasmodium parasite load (parasitemia) in blood. The acquired signals were transformed using principal of component analysis before features extracted and used for training and classification of different sample classes using machine learning models.The technique attained an overall malaria detection accuracy of 70.6% with a sensitivity of 68.4% and specificity of 72.9%. In addition, an accuracy of 100% was attained in the classification of synthetic hemozoin concentrations in whole blood samples. A total of 4200 feature vectors were used to train and test the classifiers. The training and testing set data was split in 80% to 20% respectively. Support vector machine attained the best classification accuracy. The technique was also able to yield images of sufficiently good quality to facilitate visual identification of Plasmodium parasites in unstained blood smear samples from malaria infected human subjects. The recorded performance points to the potential of PTIOSM technique potential for adoption as an optical biosensor for rapid screen of malaria and other diseases with known endogenous light absorbing molecular biomarkers.
Description
A Thesis Submitted in Fulfillment of the Requirements for the Award of the Degree of Doctor of Philosophy (Physics) in the School of Pure and Applied Sciences of Kenyatta University, August 2023.
Keywords
Photothermal Induced Optical Scattering Modulation Technique, Malaria Diagnosis