Label-Free and Real-Time Detection of Tuberculosis in Human Urine Samples Using a Nanophotonic Point-of-Care Platform

Abstract

Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Registered incidence rates are low, especially in low-resource countries with weak health systems, due to the disadvantages of current diagnostic techniques. A major effort is directed to develop a point-of-care (POC) platform to reduce TB deaths with a prompt and reliable low-cost technique. In the frame of the European POCKET Project, a novel POC platform for the direct and non-invasive detection of TB in human urine was developed. The photonic sensor is integrated in a disposable cartridge and is based on a highly sensitive Mach-Zehnder Interferometer (MZI) transducer combined with an on-chip spectral filter. The required elements for the read-out are integrated in an instrument prototype, which allows real-time monitoring and data processing. In this work, the novel POC platform has been employed for the direct detection of lipoarabinomannan (LAM), a lipopolysaccharide found in the mycobacterium cell wall. After the optimization of several parameters, a limit of detection of 475 pg/mL (27.14 pM) was achieved using a direct immunoassay in undiluted human urine in less than 15 minutes. A final validation of the technique was performed using twenty clinical samples from TB patients and healthy donors, allowing the detection of TB in people regardless of HIV coinfection. The results show excellent correlation to those obtained with standard techniques. These promising results demonstrate the high sensitivity, specificity and applicability of our novel POC platform, which could be used during routine checkups in developing countries.

Silicon‐Based Integrated Label‐Free Optofluidic Biosensors: Latest Advances and Roadmap

“…Recently, the system has also been successfully applied for tuberculosis diagnosis using clinical urine samples from patients. [ 97 ]…”

Critical assessment of relevant methods in the field of biosensors with direct optical detection based on fibers and waveguides using plasmonic, resonance, and interference effects

“…In recent years, quite a few modifications of the original Mach-Zehnder chips with implementation of phase modulation techniques, improvement of in-coupling and out-coupling have been published. By this means, real-time detection of tuberculosis in human urine samples by using a nanophotonic point-of-care platform [312]. Another interesting approach for an optical microfiber reader based on a Mach-Zehnder interferometer has been published [313].…”

Transfer-print integration of GaAs p-i-n photodiodes onto silicon nitride waveguides for near-infrared applications

“…The integration of a GaAs half-VCSEL on top of a SiN x photonic circuit has already been demonstrated using adhesive bonding and offers a low-power-consumption single-mode light source on-chip [14]. The possibility of having an integrated light source and integrated detectors on-chip will open up a range of bio-related applications, such as Optical Coherence Tomography (OCT) [15], on-chip Raman spectroscopy [16][17][18] and refractive index sensing of bio-markers through an on-chip AWG spectrometer [19][20][21]. In this work, we demonstrate the integration of GaAs p-i-n photodetectors on the imec BioPIX platform by means of µTP.…”