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    Global Health Technologies

    (I-360) Improving the Sensitivity of an Optical Cavity-Based Biosensor Using Differential Detection 

    Friday, October 13, 2023
    3:30 PM – 4:30 PM PDT
    Location: Exhibit Hall - Row I - Poster # 360
    Introduction:: Early detection of disease and monitoring its status are leading factors in increasing survival rates and reducing economic strain on patients. Therefore, the development of a low-cost, label-free, and highly sensitive diagnostic device will revolutionize medical care around the world. Enzyme-linked immunosorbent assay (ELISA) is currently used by most laboratories to detect biomarkers in the blood; however, it is costly and labor-intensive. For this reason, point-of-care (POC) biosensors have been proposed as a simple, cost-effective, rapid, and sensitive alternative for detecting biomarkers. POC biosensors are operable at the location of the patient and do not require special training, therefore the patient can monitor their health and receive rapid diagnosis and treatment from their current location, aiding patients in areas with limited medical resources to receive the care they need efficiently and affordably. We have proposed an optical cavity-based biosensor (OCB) composed of two partially reflected silver layers that provide highly sensitive detection through differential detection methods. The OCB is produced by a simple and low-cost fabrication process and contains a microfluidic channel with a biosensing surface that can detect a shift in resonance inside its cavity. The main innovation of the proposed OCB is the use of a differential detection method to improve the sensitivity by enhancing its responsivity to changes inside the cavity. In this presentation, we will show how the limit of detection (LOD) of the device can be enhanced by a differential equation that efficiently uses the opposing changes of a two-laser diode system.

    Materials and Methods:: The OCB employs a two-laser diode system involving low-cost laser diodes of 880 and 904nm, a low-cost CCD camera, and the optical cavity sample (OCS). The OCS is produced by depositing a silver layer onto two glass substrates to create partially reflective surfaces. Then, a spin-on-glass layer is spin-coated upon each silver layer and SU8 photoresist is patterned to form a gap between the substrates and define a microfluidic channel. Finally, the glass substrates are bonded with UV glue. Due to the highly sensitive nature of the optical resonator, the resonance response of the OCS shifts when a small change occurs inside the cavity. The OCS is engineered so that the intensity of the 904 nm laser diode increases while that of 880 nm laser diode decreases as the bulk and local refractive index (RI) inside the channel increases. In this experiment, a series of RI measurements were performed to demonstrate an improvement in the LOD of the device using differential detection. The bulk RI fluids of 1.33292, 1.33294, 1.33296, 1.33298, and 1.3330 were introduced to the OCS while measuring the intensities of the two laser diodes. For comparison, the individual intensity change ratios and two different differential equations (Figure 1) were used to calculate the slope of the intensity change for each RI as well as the baseline noise for the 1.33292 RI fluid. Finally, The LOD was calculated with each equation by dividing 3.3 times the baseline noise by the slope to determine the most efficient detection method.

    Results, Conclusions, and Discussions:: Initially, equations 1a and 1b were used to determine the LOD based on the intensity change ratio of each individual wavelength and yield a LOD of 1.013E-5 and 7.24E-6 respectively. Since the intensity of the individual wavelengths is changing in opposite directions, the device sensitivity can be enhanced by properly using the two-laser diode system to increase the total rate of intensity change. The differential equation, 1c, accounts for the increasing and decreasing signals by summing equations 1a and 1b to yield a LOD of 7.79E-6. Equation 1c increases the slope of the intensity change and improves the LOD from equation 1a but does not improve the LOD compared to 1b due to the subsequent increase in baseline noise from the combined signal of both wavelengths. For this reason, the equation used to determine the rate of intensity change of the decreasing signal, 1b, was modified to equation 1d to maximize the rate of intensity change and produce a larger slope for each RI. The modified equation for the decreasing signal, 1d, was then used in summation with the equation for the increasing signal, 1a, in the improved differential equation, 1e. The improved differential equation produces the largest slope of intensity change and yields a LOD of 5.52E-6, a 29% improvement from the original differential equation. The LOD from the improved differential equation is also lower than that of the individual wavelengths determined from equations 1a and 1d by 46% and 27%, respectively. The improved differential equation maximizes the opposite changes in intensity of the two-diode laser system which in turn increases the responsivity of the cavity while maintaining a low amount of outside noise to effectively enhance the LOD. In conclusion, we successfully demonstrated the capability of the proposed low-cost OCB to perform highly sensitive detection using the differential detection method. The calculated LOD of the OCB for the bulk RI measurements was 5.52E-6, which is comparable to that reported from other highly sensitive and label-free biosensors. The experimental results support that our OCB could be an effective alternative to administering early disease detection in developed and underdeveloped countries.

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