Demand for accessible and affordable healthcare for infectious and chronic diseases present significant challenges for providing high-value and effective healthcare. Traditional approaches are expanding to include point-of-care (POC) diagnostics, bedside testing, and community-based approaches to respond to these challenges.1 Innovative solutions utilizing recent advances in mobile technologies, nanotechnology, imaging systems, and microfluidic technologies are envisioned to assist this transformation.

Infectious diseases have considerable economic and societal impact on developing settings. For instance, malaria is observed more commonly in sub-Saharan Africa and India.2 The societal impact of acquired immune deficiency syndrome (AIDS) and tuberculosis is high, through targeting adults in villages and leaving behind declining populations.3 In resource-constrained settings, it is estimated that about 32% of the disease burden is from communicable diseases such as respiratory infections, AIDS, and malaria, while 43% of the burden is from noncommunicable diseases, such as cardiovascular diseases, neuropsychiatric conditions, and cancer.4 Developing diagnostic platforms that are affordable, robust, and rapid-targeting infectious diseases is one of the top priorities for improving healthcare delivery in the developing world.5 The early detection and monitoring of infectious diseases and cancer through affordable and accessible healthcare will significantly reduce the disease burden and help preserve the social fabric of these communities. Further, improved diagnostics and disease monitoring technologies have potential to enhance foreign investment, trade, and mobility in the developing countries.6

Highly sensitive and specific lab assays such as cell culture methods, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) are available for diagnosis of infectious diseases in the developed world. They require sample transportation, manual preparation steps, and skilled and well-trained technicians. These clinical conventional methods provide results in several hours to days, precluding rapid detection and response at the primary care settings. Another diagnostic challenge is identifying multiple pathogens. Since common symptoms like sore throat and fever can be caused by multiple infectious agents (e.g., bacteria and viruses), it is important to accurately identify the responsible agent for targeted treatment. Therefore, high-throughput sensors for multiplexed identification would help improve patient care.7

Medical instruments in centrally located institutions in the developed world rely on uninterrupted electricity and running water and require controlled environmental conditions. It may not be viable to satisfy some of these criteria in some POC settings, where well-trained healthcare personnel are not available and clean water access is unreliable.7,8 Further, in remote settings without infrastructure, rain and dust can act as contaminants.7 Diagnostic devices for POC testing in these settings are identified by the World Health Organization to be affordable, sensitive, user-friendly, specific to biological agents, and providing rapid response to small sample volumes.9 Optical biosensor devices are emerging as powerful biologic agent detection platforms satisfying these considerations.10

Optical sensing platforms employ various methods, including refractive index change monitoring, absorption, and spectroscopic-based measurements.11 Optical sensors that are based on refractive index monitoring cover a range of technologies, including photonic crystal fibers, nano/microring resonator structures, interferometric devices, plasmonic nano/micro arrays, and surface plasmon resonance (SPR)-based platforms.11,12 The latter two are plasmonic-based technologies. Plasmonics is an enabling optical technology with applications in disease monitoring, diagnostics, homeland security, food safety, and biological imaging applications. The plasmonic-based biosensor platforms along with the underlying technologies are illustrated in the Figure ​Figure1.1. Here, we reviewed SPR, localized surface plasmon resonance (LSPR), and large-scale plasmonic arrays (e.g., nanohole arrays).



Figure 1

Plasmonic-based technologies for versatile biosensor applications. SPR stands for surface plasmon resonance, LSPR for localized surface plasmon resonance, SPRi for surface plasmon resonance imaging, and SERS for surface-enhanced Raman scattering.

https://canarycenter.stanford.edu/content/dam/sm/canarycenter/documents/research/bamm-lab/ChemicalReview.pdf

Advances in Plasmonic Technologies for Point of Care Applications

We present and numerically characterize a closed-form multi-core holey fiber based plasmonic sensor. The coupling properties of the specific modes are investigated comprehensively by the finite element method. It is found that not only phase matching but also loss matching plays a key role in the coupling process between the fundamental mode and plasmonic mode. The coupling transforms from incomplete coupling to complete coupling with increasing analyte RI. An average sensitivity of 2929.39nm/RIU in the sensing range 1.33-1.42, and 9231.27nm/RIU in 1.43-1.53 with high linearity is obtained. The dynamic sensing range is the largest among the reported holey fiber based plasmonic sensors, to the best of our knowledge.

A multi-core holey fiber based plasmonic sensor with large detection range and high linearity

We numerically demonstrate a surface plasmon resonance biosensor-based on dual-polarized spiral photonic crystal fiber (PCF). Chemically stable gold material is used as the active plasmonic material, which is placed on the outer layer of the PCF to facilitate practical fabrication. Finite-element method-based numerical investigations show that the proposed biosensor shows maximum wavelength sensitivity of 4600 and 4300 nm/RIU in ${x}$ - and ${y}$ -polarized modes at an analyte refractive index of 1.37. Moreover, for analyte refractive index ranging from 1.33 to 1.38, maximum amplitude sensitivities of 371.5 RIU−1 and 420.4 RIU−1 are obtained in ${x}$ - and ${y}$ -polarized modes, respectively. In addition, the effects of changing pitch, different air hole diameter of the PCF and thickness of the gold layer on the sensing performance are also investigated. Owing to high sensitivity, improved sensing resolution and appropriate linearity characteristics, the proposed dual-polarized spiral PCF can be implemented for the detection of biological analytes, organic chemicals, biomolecules, and other unknown analytes.

Spiral Photonic Crystal Fiber-Based Dual-Polarized Surface Plasmon Resonance Biosensor

Flexibility in engineering holey structures and controlling the wave guiding properties in photonic crystal fibers (PCFs) has enabled a wide variety of PCF-based plasmonic structures and devices with attractive application potential. Metal thin films, nanowires, and nanoparticles are embedded for achieving surface plasmon resonance (SPR) or localized SPR within PCF structures. This paper begins with an outline of plasmonic sensing principles. This is followed by an overview of fabrication and experimental investigation of plasmonic PCFs. Reported plasmonic PCF designs are categorized based on their target application areas, including optical/biochemical sensors, polarization splitters, and couplers. Finally, design and fabrication considerations, as well as limitations due to the structural features of PCFs, are discussed.

Recent advances in plasmonic photonic crystal fibers: design, fabrication and applications

The polarization characteristics of a dual-core photonic crystal fiber (PCF) with a metal wire filled into the cladding air hole between the two cores have been investigated. Numerical investigation shows that the inclusion of the metal wire greatly changes the coupling characteristics of the modes in the two cores. In fact, the coupling lengths of the two polarizations show increased difference, which leads to the possibility of designing a dual-core PCF with a coupling length ratio of 1:2 for the two polarization states. The proposed polarization splitter shows extinction ratios as low as −20 dB with bandwidths as great as 146 nm.

Surface Plasmon Induced Polarization Splitting Based on Dual-Core Photonic Crystal Fiber with Metal Wire

We propose a novel photonic crystal fiber refractive index sensor which is based on the selectively resonant coupling between a conventional solid core and a microstructured core. The introduced microstructured core is realized by filling the air-holes in the core with low index analyte. We show that a detection limit (DL) of 2.02 × 10−6 refractive index unit (RIU) and a sensitivity of 8500 nm/RIU can be achieved for analyte with refractive index of 1.33.

Microstructured-core photonic-crystal fiber for ultra-sensitive refractive index sensing

We propose a design for a novel broadband polarization splitter based on an asymmetric dual-core square-lattice photonic-crystal fiber. The fiber is designed such that index-matched coupling between the two cores can be achieved for one polarization state, while only a part of the energy could be coupled for the other polarization state. Numerical results demonstrate that a device length of 5.9mm shows extinction ratios as low as −20dB with bandwidths as great as 101nm.

Design of broadband polarization splitter based on partial coupling in square-lattice photonic-crystal fiber

Numerical investigation on the design of a novel kind of large-mode-area optical fiber is presented. Low bending loss propagation in the fiber is achieved by the introduction of low-index rods with small period and large normalized diameter in one segment of the cladding. Single-mode operation is realized by the introduction of low-index rods with large period and small normalized diameter in another segment of the cladding. When a conventional large-mode-area optical fiber is bent, it will generally experience large bend distortion and the mode area will reduce accordingly. To avoid that, a bend-resistant design by introducing a microstructure into the solid core of the proposed fiber is proposed. In particular, the mode area of one such fiber is always larger than 2000 μ m2 when the bending radius is larger than 30 cm at the wavelength of 1.064 μm.

Bend Insensitive Design of Large-Mode-Area Microstructured Optical Fibers

We propose the design of a simple large-mode area microstructured optical fiber with low bending loss and large loss difference between the fundamental mode and the high-order modes. Single-mode operation in the fiber is realized by the introduction of small diameter holes, whereas the bending loss of the fiber is realized by the introduction of three large holes in the two-ring hole microstructured optical fiber. We also introduce low-index rods into the core of the fiber, which can effectively compensate the reduction of mode area induced by bending the fiber.

Yong-Kang Zhang

Papers

Surface Plasmon Induced Polarization Splitting Based on Dual-Core Photonic Crystal Fiber with Metal Wire

Microstructured-core photonic-crystal fiber for ultra-sensitive refractive index sensing

Design of broadband polarization splitter based on partial coupling in square-lattice photonic-crystal fiber

Bend Insensitive Design of Large-Mode-Area Microstructured Optical Fibers

Design of Asymmetric Large-mode Area Optical Fiber With Low-bending Loss