Lipoarabinomannan-based tuberculosis diagnosis using a fiber cavity ring down biosensor.

Despite existing for millennia, tuberculosis (TB) remains a persistent global health challenge. A significant obstacle in controlling TB spread is the need for a rapid, portable, sensitive, and accurate diagnostic test. Currently, sputum culture stands as a benchmark test for TB diagnosis. Although highly reliable, it necessitates advanced laboratory facilities and involves considerable testing time. In this context, we present a rapid, portable, and cost-effective optical fiber sensor designed to measure lipoarabinomannan (LAM), a TB biomarker found in patients' urine samples. Our sensing approach is based on the applications of phase shift-cavity ringdown spectroscopy (PS-CRDS) to an optical fiber cavity created by two fiber Bragg gratings. A tapered fiber is spliced inside the optical cavity to serve as the sensing head. We functionalize the tapered fiber surface with anti-LAM antigen CS-35 through a unique chemistry, creating a strong affinity for LAM molecules. We measure the phase difference between the cavity transmission and the reference modulating signal at the cavity output. The measured phase is directly proportional to the injected LAM concentrations in aqueous solutions over the sensing head. Our demonstrated sensor provides a detection limit of 10 pg/mL and a sensitivity of 0.026°/pg/mL. This sensor holds promise for numerous applications in the healthcare sector, particularly in low-resource settings.

Raman spectroscopy and machine learning-based optical probe for tuberculosis diagnosis via sputum.

Tuberculosis (TB) is a contagious disease that causes 1.5 million deaths per year globally. Early diagnosis of TB patients is critical to control its spread. However, standard TB diagnostic tests such as sputum culture take days to weeks to produce results. Here, we demonstrate a quick, portable, easy-to-use, and non-invasive optical sensor based on sputum samples for TB detection. The probe uses Raman spectroscopy to detect TB in a patient's sputum supernatant. We deploy a machine-learning algorithm, principal component analysis (PCA), on the acquired Raman data to enhance the detection sensitivity and specificity. On testing 112 potential TB patients, our results show that the developed probe's accuracy is 100% for true-positive and 93.4% for true-negative. Moreover, the probe correctly identifies patients on TB medication. We anticipate that our work will lead to a viable and rapid TB diagnostic platform.

Detection of aflatoxin M1 by fiber cavity attenuated phase shift spectroscopy.

Aflatoxin M1 (AFM1) is a carcinogenic compound commonly found in milk in excess of the WHO permissible limit, especially in developing countries. Currently, state-of-the-art tests for detecting AFM1 in milk include chromatographic systems and enzyme-linked-immunosorbent assays. Although these tests provide fair accuracy and sensitivity, they require trained laboratory personnel, expensive infrastructure, and many hours to produce final results. Optical sensors leveraging spectroscopy have a tremendous potential of providing an accurate, real-time, and specialist-free AFM1 detector. Despite this, AFM1 sensing demonstrations using optical spectroscopy are still immature. Here, we demonstrate an optical sensor that employs the principle of cavity attenuated phase shift spectroscopy in optical fiber cavities for rapid AFM1 detection in aqueous solutions at 1550 nm. The sensor constitutes a cavity built by two fiber Bragg gratings. We splice a tapered fiber of < 10 µm waist inside the cavity as a sensing head. For ensuring specific binding of AFM1 in a solution, the tapered fiber is functionalized with DNA aptamers followed by validation of the conjugation via FTIR, TGA, and EDX analyses. We then detect AFM1 in a solution by measuring the phase shift between a sinusoidally modulated laser input and the sensor output at resonant frequencies of the cavity. Our results show that the sensor has the detection limit of 20 ng/L (20 ppt), which is well below both the U.S. and the European safety regulations. We anticipate that the present work will lead towards a rapid and accurate AFM1 sensor, especially for low-resource settings.

Towards more accurate microcavity sensors: maximum likelihood estimation applied to a combination of quality factor and wavelength shifts.

Optical microcavities are widely used for biological and chemical sensing applications. In these devices, a sensing event is estimated by measuring the shift in the resonant wavelength, or in the quality factor of the microcavity. However, all published works to date only use one of these measures to estimate the sensing event. Here, we show that the estimation accuracy of a sensing event can be improved by employing a combination of both the quality factor and the resonant wavelength measurements in a microcavity sensor. We further demonstrate an experimental application of this model by introducing a refractive index change for a microtoroidal cavity sensor immersed in a liquid. By further using the finite element method simulations in conjunction with the estimator model, we show the existence of three distinct measurement regimes as a function of the quality factor of the microcavity. Finally, the estimator model is extended to develop a sensing metric to compare performance of optical or non-optical sensors.

Accurate determination of the quality factor and tunneling distance of axisymmetric resonators for biosensing applications.

Due to ultra high quality factor (10(6) - 10(9)), axisymmetric optical microcavities are popular platforms for biosensing applications. It has been recently demonstrated that a microcavity biosensor can track a biodetection event as a function of its quality factor by using phase shift cavity ring down spectroscopy (PS-CRDS). However, to achieve maximum sensitivity, it is necessary to optimize the microcavity parameters for a given sensing application. Here, we introduce an improved finite element model which allows us to determine the optimized geometry for the PS-CRDS sensor. The improved model not only provides fast and accurate determination of quality factors but also determines the tunneling distance of axisymmetric resonators. The improved model is validated numerically, analytically, and experimentally.

Simultaneous measurement of quality factor and wavelength shift by phase shift microcavity ring down spectroscopy.

Optical resonant microcavities with ultra high quality factors are widely used for biosensing. Until now, the primary method of detection has been based upon tracking the resonant wavelength shift as a function of biodetection events. One of the sources of noise in all resonant-wavelength shift measurements is the noise due to intensity fluctuations of the laser source. An alternative approach is to track the change in the quality factor of the optical cavity by using phase shift cavity ring down spectroscopy, a technique which is insensitive to the intensity fluctuations of the laser source. Here, using biotinylated microtoroid resonant cavities, we show simultaneous measurement of the quality factor and the wavelength shift by using phase shift cavity ring down spectroscopy. These measurements were performed for disassociation phase of biotin-streptavidin reaction. We found that the disassociation curves are in good agreement with the previously published results. Hence, we demonstrate not only the application of phase shift cavity ring down spectroscopy to microcavities in the liquid phase but also simultaneous measurement of the quality factor and the wavelength shift for the microcavity biosensors in the application of kinetics measurements.