Optofluidic Sensor Research Articles

In-line fiber optic optofluidic sensor based on a fully open Fabry-Perot interferometer

In-line fiber optic optofluidic sensor based on a fully open Fabry-Perot interferometer

Parallel optofluidic detection of multiple cardiac biomarkers for point-of-care testing applications

Point-of-care testing (POCT), which enables personalized, accurate, affordable, and accessible medical services, is indispensable in the diagnostics, screening, and treatment of disease, especially for emergency and severe cases. Considering the complexity of disease, multiplexed point-of-care (MPOC) testing is very important for the simultaneous detection of several biomarkers to improve accuracy and increase analysis throughput. In this work, a microfiber interferometer based multiplexed optofluidic (MIMO) chip sensor is proposed for multiplexed, quantitative detection of cardiac biomarkers. Four microfiber interferometers are suspended and fixed in four separate microscale sample channels of an imprinted polydimethylsiloxane (PDMS) chip. A drop of the sample is distributed into the four parallel channels automatically and reacts with the probe on the microfiber sensor surface specifically, which leads to the wavelength shift of the spectrum resulting from evanescent wave interactions with biomolecules. There microfiber interferometers are functionalized with myoglobin (Myo) antibody, cardiac troponin I (cTnI) antibody, and creatine kinase–myocardial band isoenzymes (CK–MB) antibody respectively and the rest microfiber interferometer is with no functionalization, which acts as the control channel to reduce noise. By using compact dedicated commercial optical modules, miniaturized and low cost experimental setup is organized and achieve four channel simultaneous measurement through time division multiplexing. Three cardiac biomarkers, Myo, cTnI, and CK–MB, are synchronously detected on the proposed MIMO chip sensor. In a standard buffer sample, the log-linear sensing range of CK–MB is 0.2 ∼ 200 ng/mL with detection limit of 3.7 pg/mL, the log-linear sensing range of Myo is 2 ∼ 2000 ng/mL with detection limit of 0.5 ng/mL, and the log-linear sensing range of cTnI 0.02 ∼ 20 ng/mL with detection limit of 2.6 pg/mL, which all perfectly cover the actual diagnostic limit of myocardial infarction. Furthermore, the MIMO chip sensor maintains excellent performance of both specificity and detection capabilities in more complex serum samples. In double-blind trials of multiple biomarker detection, the MIMO chip sensor exhibits comparable detection ability with a commercial kit and good resistance to environmental disturbance. The proposed MIMO chip sensor sensing system offers a low-cost, portable, self-driven, and miniaturized scheme for a multiplexed point-of-care testing device, promoting the feasibility and accessibility of personalized medical services and paving the way for clinical application and industrialization.

High-Q WGM microcavity-based optofluidic sensor technologies for biological analysis.

High-quality-factor (Q) optical microcavities have attracted extensive interest due to their unique ability to confine light for resonant circulation at the micrometer scale. Particular attention has been paid to optical whispering-gallery mode (WGM) microcavities to harness their strong light-matter interactions for biological applications. Remarkably, the combination of high-Q optical WGM microcavities with microfluidic technologies can achieve a synergistic effect in the development of high-sensitivity optofluidic sensors for many emerging biological analysis applications, such as the detection of proteins, nucleic acids, viruses, and exosomes. They can also be utilized to investigate the behavior of living cells in human organisms, which may provide new technical solutions for studies in cell biology and biophysics. In this paper, we briefly review recent progress in high-Q microcavity-based optofluidic sensor technologies and their applications in biological analysis.

Color-switching hydrogels as integrated microfluidic pressure sensors

Precisely measuring pressure in microfluidic flows is essential for flow control, fluid characterization, and monitoring, but faces specific challenges such as achieving sufficient resolution, non-invasiveness, or ease of use. Here, we demonstrate a fully integrated multiplexed optofluidic pressure sensor, entirely decoupled from the flow path, that enables local pressure measurements along any microfluidic channel without altering its flow geometry. The sensor itself relies on the compression of a soft mechano-actuated hydrogel, changing color in response to a pressure change. The hydrogel is separated from the fluid circulating in the channel by a thin membrane, allowing for the unrestricted use of different types of fluids. Imaging the gel through the transparent PDMS with a color camera provides a direct, easy, and contact-free determination of the fluid pressure at the sensing location for pressures as small as 20mbar with a resolution of around 10mbar. The sensitivity and accessible pressure range can be tuned via the mechanical properties of the sensing unit. The photonic gel can also be used to acquire 2D pressure or deformation maps, taking advantage of the fast response time and fine spatial resolution.

Optofluidic photonic crystal micro sensor for enhanced detection of infectious diseases

This research encompasses a comprehensive study on the application of 1D photonic crystal-based detection in the context of infectious diseases, specifically targeting malaria stages, chikungunya, and dengue. It explores the interactions between the photonic crystal and various biomolecules associated with these diseases, with a focus on platelets, plasma, and uric acid. The transmission spectrum graphs obtained from these interactions provide crucial insights into the detection and quantification of the diseases, offering real-time and label-free monitoring capabilities. Maximum sensitivity of 550 nm RIU−1 and Q factor of 29,260 obtained. Additionally, the study incorporates the design and analysis of a microfluidic channel optimized for the proposed sensor, ensuring accurate temperature and pressure distributions. The results demonstrate the feasibility of the microfluidic platform for enhancing sensor performance and fluid handling. This integrated approach shows promising potential for early disease diagnosis and monitoring, paving the way for practical implementation and further advancements in the field of sensing and diagnostics

A Cost-Effective and High-Sensitivity Optofluidic Refractive Index Sensor for Rapid Edible Oil Analysis

A Cost-Effective and High-Sensitivity Optofluidic Refractive Index Sensor for Rapid Edible Oil Analysis

Protein aggregation monitoring in microdisk optofluidic sensor through microcavity enhanced Raman scattering

Protein aggregation plays a crucial role in amyloid lesions but it is a huge challenge to monitor the slight changing process dynamically. Here, we propose an optofluidic surface-enhanced Raman scattering (SERS) sensing chip. It consists of several microdisks deposited with gold nanoparticles (Au NPs), where the microdisk acts as a whispering gallery microcavity (WGM) for light confinement and the Au NPs generate the localized surface plasma for electromagnetic enhancement. The effects of different stimulus factors on the secondary structure of lysozyme protein are revealed by observing the change of Raman spectroscopy of amide band with the enhancement of light-matter interaction. The optofluidic SERS design illuminates the potential for dynamic sensing of biological fluid and cellular microenvironment on chip.

In-situ label-free temperature-compensated DNA hybridization detection with a fiber-optic interferometer and a fiber Bragg grating for microfluidic chip

We demonstrated a temperature-compensated optofluidic DNA biosensor available for microfluidic chip. The optofluidic sensor was composed of an interferometer and a fiber Bragg grating (FBG) by femtosecond laser direct writing micro/nano processing technology. The sensing arm of the interferometer was suspended on the inner wall of the microchannel and could directly interact with the microfluid. With the immobilization of the single stranded probe DNA (pDNA), this optofluidic biosensor could achieve specific detection of single stranded complementary DNA (scDNA). The experimental results indicated that a linear response within 50 nM and the detection limit of 1.87 nM were achieved. In addition, the optofluidic biosensor could simultaneously monitor temperature to avoid temperature fluctuations interfering with the DNA hybridization detection process. And, the optofluidic detection channel could achieve fast sample replacement within 10 s at a flow rate of 2 μL/min and sample consumption only required nanoliters. This optofluidic DNA biosensor had the advantages of label-free, good specificity, dual parameter detection, low sample consumption, fast response, and easy repeatable preparation, which was of great significance for the field of DNA hybridization research and solving the temperature sensitivity problem of biosensors and had good prospects in biological analysis.

Sensitivity Equalization and Dynamic Range Expansion with Multiple Optofluidic Microbubble Resonator Sensors.

A novel multi-optofluidic microbubble resonator (OMBR) sensitivity equalization method is presented that equalizes the sensing signal from different OMBRs. The method relies on the fact that the ratio of the wavelength shifts to the bulk refractive index sensitivity (BRIS) does not depend on the physical dimensions of the OMBR. The proof of concept is experimentally validated and the sensing signals from individual OMBRs can be directly compared. Furthermore, a wide dynamic range of sensing with favorable consistency and repeatability is achieved by piecing together signals from 20 OMBRs for HIV-1 p24 antigen detection from 50 fg/mL to 100 ng/mL (2.1 fM to 4.2 nM), indicating significant potential for practical applications, such as in drug screening and disease diagnosis.

Versatile Optofluidic Fabry-Perot Sensor for Multiple Physical Parameters in Microfluidic Chips

An optofluidic sensor, which is composed of a fiber Fabry-Perot interferometer (FPI) and a microfluidic chip, is experimentally demonstrated to measure aerostatic pressure, local temperature, and fluidic flow rate in microfluidic chips. The aerostatic pressure sensitivity is as high as −2393.3 nm/Bar. By demodulating the aerostatic pressure and temperature with a sensitivity matrix, both the physical parameters can be predicted simultaneously. The noise-equivalent detection limit (NEDL) of aerostatic pressure is as low as 48.4 μBar. In addition, the experiment results show that the fluidic flow rate sensitivity is −1.8574 nm/(μl/min) and the NEDL of fluidic flow rate is 97.1 nl/min, respectively. The miniature optofluidic sensor based on the optical fiber Fabry-Perot interferometer provides a promising cost-effective sensing platform for monitoring multiple physical parameters in the microfluidic chips, which is of great significance for on-chip biochemical reactions.

Optofluidic Sensor Based on Polymer Optical Microresonators for the Specific, Sensitive and Fast Detection of Chemical and Biochemical Species.

The accurate, rapid, and specific detection of DNA strands in solution is becoming increasingly important, especially in biomedical applications such as the trace detection of COVID-19 or cancer diagnosis. In this work we present the design, elaboration and characterization of an optofluidic sensor based on a polymer-based microresonator which shows a quick response time, a low detection limit and good sensitivity. The device is composed of a micro-racetrack waveguide vertically coupled to a bus waveguide and embedded within a microfluidic circuit. The spectral response of the microresonator, in air or immersed in deionised water, shows quality factors up to 72,900 and contrasts up to 0.9. The concentration of DNA strands in water is related to the spectral shift of the microresonator transmission function, as measured at the inflection points of resonance peaks in order to optimize the signal-over-noise ratio. After functionalization by a DNA probe strand on the surface of the microresonator, a specific and real time measurement of the complementary DNA strands in the solution is realized. Additionally, we have inferred the dissociation constant value of the binding equilibrium of the two complementary DNA strands and evidenced a sensitivity of 16.0 pm/µM and a detection limit of 121 nM.

Femtosecond-laser-inscribed Bragg grating in hollow-core fiber for highly sensitive optofluidic sensing.

An optofluidic sensor based on a Bragg grating in hollow-core fiber (HCF) is experimentally demonstrated. The grating is inscribed into the HCF by femtosecond laser illumination through a phase mask. Periodic index modulation is introduced into the silica material surrounding the hollow core, causing cladding mode resonance, and multiple reflection peaks are observed in the grating spectrum. These reflection peaks later shift to longer wavelengths when high-index liquid is infiltrated into the HCF. The new reflection peak results from the backward coupling of the liquid core mode of the waveguide, the mode field of which overlaps with the grating modulation surrounding the liquid core. The resonant wavelength of the liquid-core fiber grating increases with the index value of the infiltrating liquid, and optofluidic refractive index sensing is realized with the device. The highest refractive index sensitivity, 1117 nm/RIU, is obtained experimentally in the index range of 1.476-1.54. The infiltrated hollow-core fiber Bragg grating also exhibits high temperature sensitivity due to the high thermal-optic coefficient of the liquid, and a sensitivity of -301 pm/°C is achieved in the temperature range of 25°C to 60°C.

Polished hollow core Bragg fiber sensor for simultaneous measurement of cortisol concentration and temperature.

Disturbance of surrounding temperature inevitably affects the accuracy of fiber biosensors. To that end, we propose a compact label-free optofluidic sensor based on a polished hollow core Bragg fiber (HCBF) that can simultaneously measure the cortisol concentration and surrounding temperature in real-time. The sensor is comprised of fusion splicing single mode fiber (SMF), multimode fiber (MMF) and HCBF. HCBF is side polished to remove part of the cladding that the suspended inner surface of the fiber can contact the external environment. After the incident light passes through the MMF from the SMF, it enters the hollow area, high refractive index (RI) layers, respectively, where the anti-resonant reflecting optical waveguide (ARROW) guiding mechanism and Mach-Zehnder interferometer (MZI) are simultaneously excited. Taking advantage of the high RI layers of HCBF, compared to the fiber with uniform cladding, the light can be more confined in the cladding and more sensitive to inner surface medium. The inner surface of sensor is immobilized with cortisol aptamer for the sake of achieving high sensitivity and specific sensing of cortisol with the limit of detection (LOD) to be 4.303 pM. The proposed sensor has a compact structure, enables temperature compensation, and can be fabricated at low cost making it highly suitable for in-situ monitoring and high-precision sensing of cortisol and other biological analytes.

Design of an optofluidic sensor based on metamaterial absorbers for detection of organic materials

Design of an optofluidic sensor based on metamaterial absorbers for detection of organic materials

Optofluidic laser sensor for the detection of dopamine

Dopamine (DA) is a biomarker of many psychiatric diseases, such as schizophrenia and Parkinson's disease. Most current DA detection research adopts electrochemical method, which suffers interferences caused by many analogs with similar structures or redox potentials. To realize highly sensitive and selective DA sensing, herein we propose an optofluidic-laser-based DA sensor. Via the competitive adsorption mechanism, rhodamine 6G (Rh6G) is fixed on graphene oxide (GO) and replaced by DA in the sample, with the re-excited Rh6G serving as the gain medium of the optofluidic laser. As the DA concentration increases, more Rh6G is released into the sample, which induces an increase in the relative slope efficiency of the optofluidic laser and a reduction in the laser threshold. Both the relative slope efficiency and threshold attain a suitable linear relationship with the DA concentration within the 5–800 μM range. Under ideal circumstances, the detection limit of the biosensor is 0.3 µM. Moreover, the optofluidic laser-based biosensor achieves favorable selectivity for DA detection, proving the advantages of using optical laser sensors for DA detection in complex samples.

Real-Time Measurement of Refractive Index Using 3D-Printed Optofluidic Fiber Sensor

This work describes a 3D-printed optofluidic fiber sensor to measure refractive index in real time, combining a microfluidic system with an optical fiber extrinsic Fabry-Perot interferometer. The microfluidic chip platform was developed for this purpose through 3D printing. The Fabry-Perot cavity was incorporated in the microfluidic chip perpendicularly to the sample flow, which was of approximately 3.7 µL/s. The optofluidic fiber sensor platform coupled with a low-cost optical power meter detector was characterized using different concentrations of glucose solutions. In the linear regression analysis, the optical power shift was correlated with the refractive index and a sensitivity of -86.6 dB/RIU (r2 = 0.996) was obtained. Good results were obtained in terms of stability with a maximum standard deviation of 0.03 dB and a sensor resolution of 5.2 × 10-4 RIU. The feasibility of the optofluidic fiber sensor for dynamic analyses of refractive index with low sample usage was confirmed through real-time measurements.

Optofluidic Fabry-Perot interferometric sensor for the real-time measurement of refractive index

In this work, a microfluidic system combined with a fibre-optic extrinsic Fabry-Perot interferometer is proposed to measure refractive index continuously and in real time. A microfluidic platform was designed and created for this purpose through 3D printing. The Fabry-Perot cavity is an integral part of the microfluidic chip and is perpendicular to the sample flow. The light is conducted through a single mode optical fibre and the refractive index measurements were based on the optical power and wavelength shift of the reflected spectra. The developed optofluidic setup was characterised using different concentrations of glucose solutions. A sensitivity of 1102 nm/RIU was obtained when using the wavelength shift, however, when the same solution was analysed over time, the signal for wavelength shift measurements was found to be unstable. The optical power shift was correlated with the refractive index and a sensitivity of -79.6 dB/RIU was obtained, with a good linearity (r2 = 0.996). Good results were verified in terms of stability with a maximum standard deviation of 0.028 dB and a sensor resolution of 4.3×10−4 RIU. This sensor has a great potential for applications in which refractive index real-time measurements are required, such as food and beverages industry process control.

Microfluid Switching-Induced Transient Refractive Interface.

The laminar flow interface (LFI) developed at low Reynolds numbers is one of the most prominent features of microscale flows and has been employed in a diverse range of optofluidic applications. The formation of LFIs usually requires the manipulation of multiple streams within a microchannel using a complex hydrodynamic pumping system. Herein, we present a new type of LFI that is generated by fluid switching within a three-dimensional (3D) microlens-incorporating microfluidic chip (3D-MIMC). Since Poiseuille flows exhibit a parabolic velocity profile, the LFI is cone-like in shape and acts as a transient refractive interface (TRI), which is sensitive to the refractive index (RI) and the Péclet number (Pe) of the switching fluids. In response to the TRI, the intensity of the transmitted light can be intensified or attenuated depending on the sequence of fluid switching operations. By incorporating three-dimensional (3D) microlenses and increasing the Pe values, the profile and amplitude of the intensity peak are both significantly improved. The limit of detection (LoD) for a sodium chloride (NaCl) solution at Pe = 1363 is as low as 0.001% (w/w), representing an improvement of 1-2 orders of magnitude when compared to existing optofluidic concentration sensors based on intensity modulation. Fluid switching of a variety of inorganic and organic sample fluids confirms that the specific optical response (Kor) correlates positively with both Pe and the specific RI (Knc), obeying a linear relationship. This model is further verified through cross-validations and used to estimate the molecular diffusion coefficient (D) of a range of species. Furthermore, by virtue of the TRI, we achieve a sensitive measurement of optical-equivalent total dissolved solids (OE-TDS) for environmental samples.

Duplex detection of foodborne pathogens using a SERS optofluidic sensor coupled with immunoassay

Herein, we developed a surface-enhanced Raman spectroscopy (SERS) optofluidic sensor coupled with immunoprobes to simultaneously separate and detect the foodborne pathogens, Escherichia coli O157:H7, and Salmonella in lettuce and packed salad. The method consists of three steps of (i) enrichment to enhance detection sensitivity, (ii) selective separation and labelling of target bacteria by their specific antibody-bearing SERS-nanotags and (iii) detection of tagged bacterial cells using SERS within a hydrodynamic flow-focusing SERS optofluidic device, where even low counts of bacterial cells were detectable in the very thin-film-like sample stream. SERS-nanotags consisted of different Raman reporter molecules, representing each species, i.e., the detection of Raman reporter confirms the presence of the target pathogen. The anti-E. coli antibody used in this study functions against all strains of E. coli O157:H7 and the anti-Salmonella antibody used in this work acts on a wide range of Salmonella enterica strains. Bacterial counts of 1000, 100, and 10 CFU/ 200 g sample were successfully detected after only 15 min enrichment. Our method showed a very low detection limit value of 10 CFU/ 200 g sample for the bacterial mixture in both lettuce and packed salad, proving the efficiency and high sensitivity of our method to detect multiple pathogens in the food samples. The total analysis time, including sample preparation for simultaneous detection of multiple bacteria, was estimated to be 2 h, which is much less than the time required in conventional methods. Hence, our proposed protocol is considered a promising rapid and efficient approach for pathogen screening of food samples.

Optical Identification of Parenteral Nutrition Solutions Exploiting Refractive Index Sensing

Parenteral artificial nutrition (PAN) is a lifesaving treatment for a large population of patients affected by different diseases, and it consists of intravenous injection of nutritive fluids by means of infusion pumps. Wrong PAN solutions are, unfortunately, often administered, thus threatening the patients’ well-being. Here, we report an optofluidic label-free sensor that can distinguish PAN solutions on the basis of their volumetric refractive index (RI). In our system, a monochromatic light beam, generated by a laser diode, travels obliquely through a transparent, square-section polystyrene channel, is then back-reflected by a mirror, and finally exits the channel in a position that depends on the filling fluid RI. The displacement of the output light spot ΔXexperim is easily detected with a linear, 1-D position sensitive detector (PSD). We initially calibrated the sensor with water-glucose solutions demonstrating a sensitivity S = ΔXexperim/Δn = 13,960 µm/RIU. We then clearly distinguished six commercial PAN solutions, commonly administered to patients. To the best of our knowledge, this is the first reported healthcare sensing platform for remote contactless recognition of PAN fluids, which could be inserted into infusion pumps to improve treatment safety, by checking the compliance to the prescription of the fluid actually delivered to the patient.