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While paper-based rapid tests are abundantly used in medicine, their performance is limited by the poor limit of detection and binary response of the test. We have previously shown that interpreting rapid tests based on laser-induced photothermal responses can offer over an order magnitude improvement in test performance. This work reports on miniaturization of our photothermal sensing paradigm in a low-cost handheld device and its field validations. The hand-held device excites assay gold nanoparticles with a modulated, low-power LED while recording their thermal wave responses with low-cost single-element sensors. An Arduino-based processor demodulates thermal wave responses while offering internet-of-things capability. Results from a human study on detection and quantification of Cannabis consumption will also be presented and discussed.
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Tissue biopsy, the sampling of human cells using surgery, constitutes a significant barrier to easy and frequent monitoring of cancer patients. In liquid biopsy, the blood of cancer patients is instead sampled to monitor the level of cancer biomarkers. Detecting nucleic acid biomarkers for cancer diagnosis requires the enzymatic amplification of sequences to be identified to achieve the needed level of sensitivity. Such a step introduces constraints and drawbacks in the assays, and efforts have been made to identify innovative amplification-free protocols for DNA detection. The possibilities offered by nanoparticle-enhanced surface plasmon resonance imaging in detecting non-amplified DNA circulating in cancer patients’ blood will be discussed in the context of applications to cancer diagnosis based on liquid biopsy. The role played by the proper design of the plasmonic sensor surface will also be discussed with specific emphasis on a new dual-functional low-fouling poly-L-lysine-based surface layer.
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Continuous glucose monitoring is essential for improving the quality of life for diabetes patients. Current glucose sensors have limited lifespans, prompting the need for innovative solutions. Our research introduces a novel approach by combining a biocompatible hydrogel with gold nanostructures for glucose sensing. The transparent hydrogel incorporates 3-(Acrylamido)phenylboronic acid, a glucose-responsive component that changes the hydrogel's dimension by forming covalent bonds with 1,2-cis-diol. Gold nanostructures are synthesized using femtosecond laser multiphoton photoreduction, with characteristics varying based on incident laser power, line spacing, and 3D configuration. These metallic nanostructures exhibit shifting absorption spectra corresponding to glucose concentration changes. To enhance sensitivity to lower glucose levels, hydrogels can be further modified with tertiary amines. This hydrogel-based plasmonic sensor presents substantial promise for advancing hydrogel-based glucose monitoring.
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Lab-on-Fiber (LoF) technology is a research field aimed at transforming a simple optical fiber into a multifunctional probe, which exploits enhanced light-matter interaction for a variety of applications, with special aptitude for biosensing. An attractive thread in this scenario is the integration of plasmonic metasurfaces onto an optical fiber tip, known as optical fiber “meta-tips”, leading to the development of a new generation of highly sensitive optrodes. Here we report on the latest achievements concerning the investigation of LoF probes assisted by plasmonic phase-gradient metasurfaces for the detection of small molecules as well as clinically relevant cancer biomarkers in the picomolar range. The high biosensing performance, joined with huge potential for miniaturization and integration, makes this platform an excellent candidate for the development of Point-of-Care (PoC) devices aimed at real-time and label-free detection of clinically relevant biomarkers offering several advantages over conventional procedures.
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We present the SERS-based detection of biomolecules in complex biological matrices. This includes the detection of co-factors in bacterial membranes, drugs and its metabolites in clinically relevant matrices as well as cancer-relevant marker in saliva. To overcome the complexity of the biological matrix, a high affinity of the target analyte is essential, which is improved by sample preparation processes or specific enrichment on the sensor surface.
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Interferometric scattering microscopy is a breakthrough in ultrasensitive, label-free detection of biomolecules enabled by fast and sensitive imaging of light scattered by weakly scattering objects. Our research focuses on discerning subtle fluctuations in the scattering signal to describe biomolecular interactions and processes hidden deep within the subdiffractional volume of the probe beam. We demonstrate how the fluctuation in the scattering amplitude can be associated with conformation changes taking place at the level of a single, or a few unlabeled biomolecules and open new possibilities for the next generation of super-resolution microscopy techniques. We further combine the ultrasensitive detection of single molecules with real-time Raman spectroscopy to monitor the structural fluctuations on the single-molecule level. Understanding the dynamics of biological matter opens new avenues in label-free super-resolution microscopy and ultimately sensitive detection and identification of biomolecular samples.
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Metal nano-hole arrays, modulating resonances intensity and spectral position, span visible to near-infrared ranges, unlocking sensing applications. Displacing electric fields toward the interface with air, facilitated by a high-index material (SiN) substrate, refines the sensitive region and improve enhancement. Efficient and reproducible fabrication protocols, such as the modified nanosphere lithography (NSL) method, have been developed by our group for the creation of highly ordered nano-hole arrays (NHAs) in thin gold films. These arrays feature diverse properties, including thickness, hole shape, diameter, and lateral periodic or quasi-periodic spacing. Interference and coupling between plasmonic modes of different natures present a route for enhancement for SERS applications. Integrating these nanostructures within a fiber-based microfluidic system offers an innovative solution for pesticide detection. This system, characterized by straightforward fabrication, cost-effectiveness, sensitivity, and specificity, emerges as a formidable contender for in-situ environmental monitoring, encapsulating cutting-edge research and innovation in pest control.
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The development of biochemical sensing devices that can achieve simple and fast detection with high sensitivity and specificity would significantly facilitate the efficiency for environmental monitoring. Optical sensors based on surface plasmon resonance (SPR) effect can provide several advantages that other sensors are difficult to achieve such as real-time and label-free sensing. Current SPR approaches are incapable of detecting small particles with toxins (bacteria and heavy metal ions) at a low concentration level. In this context, we will aim at the use of phase singularity enhanced optical signal to achieve a compact and more sensitive detection. By taking up this challenge, it would allow us to engineer the sensing chips in a resolution of sub-nanometer and realize an efficient and compact sensor for environmental monitoring for small pollutants.
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Enabling Technologies for Instrumentation and Lab on a Chip I
Multidrug-resistant bacteria stem from the massive use of non-specific antibiotics prescribed to manage bacterial infections. The therapeutic use of viruses called bacteriophages is a promising complementary and personalised strategy requiring very accurate phage selection for patient administration. Therefore, we are developing an interdisciplinary methodology for phage susceptibility testing (PST) based on bio-photonic microsystems. We demonstrated the use of on-chip optical photonic crystals on silicon-on-insulator (SOI) for the spatial confinement of bacteria and phages. We will present our state of the art of this project and the methods currently used to study the interactions between SOI and biological objects.
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In this work we propose a high quality optofluidic Fabry- Perot (FP) microcavity, entirely fabricated by using low-cost polymeric materials. The cavity, the mirrors and the substrates, including the microfluidic layer, are assembled by a simple and low-cost lamination process. The cavity length is L=50 µm. By exploring the different polymeric mirrors, resonators with quality factor up Q=1.8 ×105 and finesse of F=486 have been obtained. Refractometric sensing capability of about 300 nm/RIU has been measured. The straightforward fabrication, high quality factor (Q), and small modal volume, makes the proposed optofluidic FPs very promising in sensing applications of liquid sample, including biomedical and environmental monitoring.
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Enabling Technologies for Instrumentation and Lab on a Chip II
Recent years have seen a rising interest in the advancement of versatile plasmonic devices due to their lightweight, cost-effectiveness, and enhanced flexibility compared to traditional rigid substrates like glass or silicon. Plasmonic devices excel in controlling and amplifying the electromagnetic field at optical frequencies, particularly at the metal-dielectric interface on a nanoscale. This capability significantly improves the performance of analytical tools such as fluorescence microscopy and spectrometry. Nanostructured plasmonic devices have found substantial applications in fields like biology, medicine, and bioengineering for the analysis of biological samples. The study discusses the fabrication of thin, flexible plasmonic devices using
polydimethylsiloxane (PDMS) with gold nanoparticle clusters, integrated with a microfluidic circuit for rapid and efficient analyses, successfully detecting anti-human immunoglobulins G (IgG) in solution.
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Frequent blood donors are therefore at an increased risk of developing iron deficiency. Currently, there is no easy and routinely available method during blood donation to detect iron deficient erythropoiesis (IDE) before the amount of healthy red blood cells drops below normal levels, which is referred to as anemia. An optical technology to detect iron deficiency in a pre-anemic state had been developed. The measurement is performed on the tubing between the donor and the blood collection bag during the donation. The measurement takes about 1 minute and provides an immediate result at very low costs. The evaluation showed a high sensitivity to identify blood donors with advanced iron deficiency before anemia occurs. The method was shown to be more sensitive than the standard assessment of the hemoglobin value. The optical method envisioned the feasibility and diagnostic value to prevent iron deficiency anemia of frequent blood donors by providing an early warning signal. Beyond the health benefit for the blood donor, this might also lead to less rejections of blood donors due to iron deficiency anemia.
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