An official website of the United States government
Although many advanced biosensing techniques have been proposed for cytokine profiling, there are no clinically available methods that integrate high-resolution immune cell monitoring and in situ multiplexed cytokine detection together in a biomimetic tissue microenvironment. The primary challenge arises due to the lack of suitable label-free sensing techniques and difficulty for sensor integration. In this work, we demonstrated a novel integration of a localized-surface plasmon resonance (LSPR)-based biosensor with a biomimetic microfluidic ‘adipose-tissue-on-chip’ platform for an in situ label-free, high-throughput and multiplexed cytokine secretion analysis of obese adipose tissue. Using our established adipose-tissue-on-chip platform, we were able to monitor the adipose tissue initiation, differentiation, and maturation and simulate the hallmark formation of crown-like structures (CLSs) during pro-inflammatory stimulation. With integrated antibody-conjugated LSPR barcode sensor arrays, our platform enables simultaneous multiplexed measurements of pro-inflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10 and IL-4) cytokines secreted by the adipocytes and macrophages. As a result, our adipose-tissue-on-chip platform is capable of identifying stage-specific cytokine secretion profiles from a complex milieu during obesity progression, highlighting its potential as a high-throughput preclinical readout for personalized obesity treatment strategies.
more »
« less
Intensity-modulated nanoplasmonic interferometric sensor for MMP-9 detection
To elucidate the secretary function of immune cells, we develop a nanoplasmonic circular interferometric biosensor based on intensity interrogation for label-free and dynamic sensing of molecular secretion. Exceptional sensitivity has been demonstrated through coupling free light and surface plasmon polariton (SPPs) waves, which generates a constructive and deconstructive interference pattern with high contrast and narrow linewidth when illuminated by white light. Alternatively, by adopting a narrow-band LED source and a CCD camera in this work, the transmission intensity of multiple sensing units is monitored simultaneously with a simple collinear optical setup. This intensity-modulated sensing platform yields a resolution of 4.1 × 10 −5 refractive index unit (RIU) with a high temporal resolution of 1 s and a miniaturized footprint as small as 9.8 × 9.8 μm 2 for a single sensing unit. By integrating the signals from multiple sensor units, the resolution of a 12 × 12 sensor array was found to reach 7.3 × 10 −6 RIU. We apply this sensor array to detect matrix metalloproteinase 9 (MMP-9) secretion from human monocytic cells, THP-1, at different time points after lipopolysaccharide (LPS) simulation and the results are in good agreement with enzyme-linked immunosorbent assay (ELISA) tests, but without the need for labeling. The spatial, temporal and mass resolutions of the sensor array are found to exceed other label-free technologies. These biomolecular arrays, incorporated in a microfluidic sensor platform, hold great potential for the study the dynamics and interplay of cell secretion signals and achieving a better understanding of single cell functions.
more »
« less
- Award ID(s):
- 1718177
- PAR ID:
- 10112606
- Date Published:
- Journal Name:
- Lab on a Chip
- Volume:
- 19
- Issue:
- 7
- ISSN:
- 1473-0197
- Page Range / eLocation ID:
- 1267 to 1276
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract MotivationCell communication is predominantly governed by secreted proteins, whose diverse secretion patterns often signify underlying physiological irregularities. Understanding these secreted signals at an individual cell level is crucial for gaining insights into regulatory mechanisms involving various molecular agents. To elucidate the array of cell secretion signals, which encompass different types of biomolecular secretion cues from individual immune cells, we introduce the secretion-signal map (S2Map). ResultsS2Map is an online interactive analytical platform designed to explore and interpret distinct cell secretion-signal patterns visually. It incorporates two innovative qualitative metrics, the signal inequality index and the signal coverage index, which are exquisitely sensitive in measuring dissymmetry and diffusion of signals in temporal data. S2Map’s innovation lies in its depiction of signals through time-series analysis with multi-layer visualization. We tested the SII and SCI performance in distinguishing the simulated signal diffusion models. S2Map hosts a repository for the single-cell’s secretion-signal data for exploring cell secretio-types, a new cell phenotyping based on the cell secretion signal pattern. We anticipate that S2Map will be a powerful tool to delve into the complexities of physiological systems, providing insights into the regulation of protein production, such as cytokines at the remarkable resolution of single cells. Availability and implementationThe S2Map server is publicly accessible via https://au-s2map.streamlit.app/.more » « less
-
Abstract Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5–45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due to the interaction of the propagating light in the evanescent field with glucose molecules. The coating of the TOF with gold nanoparticles (AuNPs) as an active layer for glucose sensing generated LSPR through the interaction of the evanescent wave with AuNPs deposited at the tapered waist. The results indicated that the TOF (Ø = 5 µm) exhibited improved sensing performance with a sensitivity of 1265%/RIU compared to the TOF (Ø = 12 µm) at 560%/RIU towards glucose. The AuNPs were characterized using scanning electron microscopy and ultraviolent-visible spectroscopy. The AuNPs-decorated TOF (Ø = 12 µm) demonstrated a high sensitivity of 2032%/RIU toward glucose. The AuNPs-decorated TOF sensor showed a sensitivity enhancement of nearly 4 times over TOF (Ø = 12 µm) with RI ranging from 1.328 to 1.393. The fabricated TOF enabled ultrasensitive glucose detection with good stability and fast response that may lead to next-generation ultrasensitive biosensors for real-world applications, such as disease diagnosis.more » « less
-
Abstract Silicon photonic index sensors have received significant attention for label-free bio and gas-sensing applications, offering cost-effective and scalable solutions. Here, we introduce an ultra-compact silicon photonic refractive index sensor that leverages zero-crosstalk singularity responses enabled by subwavelength gratings. The subwavelength gratings are precisely engineered to achieve an anisotropic perturbation-led zero-crosstalk, resulting in a single transmission dip singularity in the spectrum that is independent of device length. The sensor is optimized for the transverse magnetic mode operation, where the subwavelength gratings are arranged perpendicular to the propagation direction to support a leaky-like mode and maximize the evanescent field interaction with the analyte space. Experimental results demonstrate a high wavelength sensitivity of − 410 nm/RIU and an intensity sensitivity of 395 dB/RIU, with a compact device footprint of approximately 82.8 μm2. Distinct from other resonant and interferometric sensors, our approach provides an FSR-free single-dip spectral response on a small device footprint, overcoming common challenges faced by traditional sensors, such as signal/phase ambiguity, sensitivity fading, limited detection range, and the necessity for large device footprints. This makes our sensor ideal for simplified intensity interrogation. The proposed sensor holds promise for a range of on-chip refractive index sensing applications, from gas to biochemical detection, representing a significant step towards efficient and miniaturized photonic sensing solutions. Graphical Abstractmore » « less
-
State-of-the-art tactile sensing arrays are not scalable to large numbers of sensing units due to their raster-scanned process. This interface process results in a high degree of wiring complexity and a tradeoff between spatial and temporal resolution. In this paper, we present a new neuromimetic tactile sensing scheme that allows for single-wire signal transduction and asynchronous signal transmission - without the incorporation of electronics into each sensing element. A prototype device with spatial frequency encoding was developed using flexible fabric-based e-textile materials, and the ability of this new sensing scheme was demonstrated through a texture discrimination task. Overall, the neuromimetic spatial frequency encoded sensor array had comparable performance to the state-of-the-art tactile sensor array and achieved a classification accuracy of 86.58%. Future tactile sensing systems and electronic skins can emulate the spatial frequency encoding architecture presented here to become dense and numerous while retaining excellent temporal resolution.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C8LC01391H
