Metasurface is a recently developed nanophotonics concept to manipulate the properties of light by replacing conventional bulky optical components with ultrathin (more than 10 ⁴ times thinner) flat optical components. Since the first demonstration of metasurfaces in 2011, they have attracted tremendous interest in the consumer optics and electronics industries. Recently, metasurface‐empowered novel bioimaging and biosensing tools have emerged and been reported. Given the recent advances in metasurfaces in biomedical engineering, this review article covers the state of the art for this technology and provides a comprehensive interdisciplinary perspective on this field. The topics that we have covered include metasurfaces for chiral imaging, endoscopic optical coherence tomography, fluorescent imaging, super‐resolution imaging, magnetic resonance imaging, quantitative phase imaging, sensing of antibodies, proteins, DNAs, cells, and cancer biomarkers. Future directions are discussed in twofold: application‐specific biomedical metasurfaces and bioinspired metasurface devices. Perspectives on challenges and opportunities of metasurfaces, biophotonics, and translational biomedical devices are also provided. The objective of this review article is to inform and stimulate interdisciplinary research: firstly, by introducing the metasurface concept to the biomedical community; and secondly by assisting the metasurface community to understand the needs and realize the opportunities in the medical fields. In addition, this article provides two knowledge boxes describing the design process of a metasurface lens and the performance matrix of a biosensor, which serve as a “crash‐course” introduction to those new to both fields.

Molecular vibrations play a crucial role in physical chemistry and biochemistry, and Raman and infrared spectroscopy are the two most used techniques for vibrational spectroscopy. These techniques provide unique fingerprints of the molecules in a sample, which can be used to identify the chemical bonds, functional groups, and structures of the molecules. In this review article, recent research and development activities for molecular fingerprint detection using Raman and infrared spectroscopy are discussed, with a focus on identifying specific biomolecules and studying the chemical composition of biological samples for cancer diagnosis applications. The working principle and instrumentation of each technique are also discussed for a better understanding of the analytical versatility of vibrational spectroscopy. Raman spectroscopy is an invaluable tool for studying molecules and their interactions, and its use is likely to continue to grow in the future. Research has demonstrated that Raman spectroscopy is capable of accurately diagnosing various types of cancer, making it a valuable alternative to traditional diagnostic methods such as endoscopy. Infrared spectroscopy can provide complementary information to Raman spectroscopy and detect a wide range of biomolecules at low concentrations, even in complex biological samples. The article concludes with a comparison of the techniques and insights into future directions.

Blood flow is an important indicator of human health status. Compromised blood flow may cause diseases, such as stroke,¹ foot ulcer,² and myocardial ischemia.³ Several optical technologies have been developed for blood flow measurement. Laser speckle contrast imaging (LSCI) methods^4,5 have been developed for wide-field blood flow imaging of superficial tissue ($\sim 1\mathrm{mm}$).⁵ It is a powerful tool for visualization of blood vessels. However, the penetration depth limits its applications in deep tissue blood flow measurement. Since biological tissue is a highly scattering medium for light, several diffuse optical methods have been developed for blood flow measurement in deep tissue (up to $\sim 15\mathrm{mm}$).⁶ Diffuse correlation spectroscopy (DCS)^{6 – 9} is one of the first noninvasive optical methods; it has been used to monitor deep tissue blood flow in human muscle,¹⁰ brain,¹¹ and breast cancer.¹² DCS has many advantages including noninvasiveness, portability, and high temporal resolution (up to $\sim 100\mathrm{Hz}$).⁶ However, there are challenges for DCS systems. To acquire the intensity temporal autocorrelation function $G_2(\tau )$, a single-mode (SM) fiber and a high-sensitivity single-photon counting avalanche photodiode (SPC-APD) have to be used for photon detection. To extend DCS into multiple channels, each detection channel requires one SPC-APD, which increases the hardware cost significantly. Diffuse speckle contrast analysis (DSCA) was developed as a cost-effective method for deep tissue blood flow measurement.^{13 – 16} DSCA uses the relationship between the speckle contrast of the diffused laser light and the blood flow index (BFI) in DCS to achieve a level of deep tissue blood flow measurements similar to that of DCS.^13,17,18 The fiber-based DSCA system can be extended into multiple channels without significant additional cost.¹⁷ Several other deep tissue blood flow measurement modalities based on diffused laser speckle detection have been developed. Speckle contrast optical tomography^19,20 achieves three-dimensional imaging of deep tissue blood flow. Diffuse speckle contrast flowmeter²¹ achieves a wearable sensor for cerebral blood flow monitoring in small animals.

The flexibile nature of optical fiber enables it to offer remote-access capabilities, which could be used in many biomedical applications. This review focuses on different micro- and nano-structured fiber probes for applications in biosensing, imaging, and stimulations. The modifications to fiber could extend design freedom from waveguide optimization to functional material integration. Fiber probes with optimized waveguide structures or integrated functional materials could achieve enhanced optical mode interaction with biosamples, and hence obtain ultrasensitive biosensors with a remarkably low limit of detection. Furthermore, bioimaging with a high spatial resolution can be obtained by engineering dispersion and nonlinearity of light propagation in the fiber core or designing a metal-coated tapered fiber tip with a sub-wavelength aperture. Flat metasurfaces can be assembled on a fiber tip to achieve a large depth of focus and remove aberrations. Fiber is also a compact solution to realize the precise delivery of light for in vivo applications, such as deep brain stimulation. The optical beam size, shape, and direction could be steered by the probe parameters. Micro- and nano-technologies integrated with fiber contribute to various approaches to further improve detection limit, sensitivity, optical resolution, imaging depth, and stimulation precision.

The detection of volatile organic compounds (VOCs) has emerged as one of the most promising diagnostic approaches in the field of medicine. For example, human breath contains endogenous volatiles that could be potential biomarkers. The demand for the cost-effective, noninvasive, and sensitive detection of VOCs has increased significantly following the recent COVID-19 pandemic. Typically, VOCs are detected using the gold-standard technology of gas chromatography and mass spectrometry, but this equipment can be bulky and expensive outside of laboratory settings. In this context, biophotonics (or optical) technologies play a crucial role as they can provide highly sensitive detection of VOCs in a cost-effective manner and are suitable for developing point-of-care devices. This review critically and comprehensively analyzes the recent advancements (over the last decade) in biophotonics technologies for the detection of VOCs, such as surface-enhanced Raman spectroscopy, fluorescence spectroscopy, laser absorption spectroscopy, photoacoustic spectroscopy, and surface plasmon resonance, with a special focus on healthcare applications. Relative merits and demerits of these techniques are provided by comparing their sensitivity, limit of detection, and methodology in operation. Finally, the review highlights future perspectives on technical advancements and gaps in research that need to be addressed to translate these biophotonics technologies into a routine VOC-based disease diagnostic platform.

Confocal Raman spectroscopy (CRS) is a powerful tool that has been widely used for biological tissue analysis because of its noninvasive nature, high specificity, and rich biochemical information. However, current commercial CRS systems suffer from limited detection regions (450–1750 cm^–1), bulky sizes, nonflexibilities, slow acquisitions by consecutive excitations, and high costs if using a Fourier transform (FT) Raman spectroscopy with an InGaAs detector, which impede their adoption in clinics. In this study, we developed a portable CRS system with a simultaneous dual-wavelength source and a miniaturized handheld probe (120 mm × 60 mm × 50 mm) that can acquire spectra in both fingerprint (FP, 450–1750 cm^–1) and high wavenumber (HW, 2800–3800 cm^–1) regions simultaneously. An innovative design combining 671 and 785 nm lasers for simultaneous excitation through a compact and high-efficiency (>90%) wavelength combiner was implemented. Moreover, to decouple the fused FP and HW spectra, a first-of-its-kind precise Raman spectra separation algorithm (PRSSA) was developed based on the maximum a posteriori probability (MAP) estimate. The accuracy of spectra separation was greater than 99%, demonstrated in both phantom experiments and in vivo human skin measurements. The total data acquisition time was reduced by greater than 50% compared to other CRS systems. The results proved our proposed CRS system and PRSSA’s superior capability in fast and ultrawideband spectra acquisition will significantly improve the integration of CRS in the clinical workflow.