Direct Thermal Growth of Gold Nanopearls on 3D Interweaved Hydrophobic Fibers as Ultrasensitive Portable SERS Substrates for Clinical Applications.

Surface-enhanced Raman spectroscopy (SERS)-based biosensors have attracted much attention for their label-free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a wafer-scale, ultrasensitive, highly uniform, paper-based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow-surface-energy fluorosilane-modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as-designed paper-based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011 ), detectability at sub-femtomolar concentrations (single-molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785-nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzo[a]pyrene, benzo[g,h,i]perylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub-ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra-early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on-site detection in biofluid analysis, point-of-care diagnostics and precision medicine.

Thickness-Sensing Sandwiched Plasmonic Biosensors Enable Label-Free Naked-Eye Antibody Quantification.

Clinical serology assays for detecting the antibodies of the virus are time-consuming, are less sensitive/selective, or rely on sophisticated detection instruments. Here, we develop a sandwiched plasmonic biosensor (SPB) for supersensitive thickness-sensing via utilizing the distance-dependent electromagnetic coupling in sandwiched plasmonic nanostructures. SPBs quantitatively amplify the thickness changes on the nanoscale range (sensitivity: ∼2% nm-1) into macroscopically visible signals, thereby enabling the rapid, label-free, and naked-eye detection of targeted biomolecular species (via the thickness change caused by immunobinding events). As a proof of concept, this assay affords a broad dynamic range (7 orders of magnitude) and a low LOD (∼0.3 pM), allowing for the extremely accurate SARS-CoV-2 antibody quantification (sensitivity/specificity: 100%/∼99%, with a portable optical fiber device). This strategy is suitable for high-throughput multiplexed detection and smartphone-based sensing at the point-of-care, which can be expanded for various sensing applications beyond the fields of viral infections and vaccination.

Plasmonic Biosensors with Nanostructure for Healthcare Monitoring and Diseases Diagnosis.

Nanophotonics has been widely utilized in enhanced molecularspectroscopy or mediated chemical reaction, which has major applications in the field of enhancing sensing and enables opportunities in developing healthcare monitoring. This review presents an updated overview of the recent exciting advances of plasmonic biosensors in the healthcare area. Manufacturing, enhancements and applications of plasmonic biosensors are discussed, with particular focus on nanolisted main preparation methods of various nanostructures, such as chemical synthesis, lithography, nanosphere lithography, nanoimprint lithography, etc., and describing their respective advances and challenges from practical applications of plasmon biosensors. Based on these sensing structures, different types of plasmonic biosensors are summarized regarding detecting cancer biomarkers, body fluid, temperature, gas and COVID-19. Last, the existing challenges and prospects of plasmonic biosensors combined with machine learning, mega data analysis and prediction are surveyed.

Plasmonic sensing using metallic nano-sculptured thin films.

Nano-sculptured thin films (nSTFs) is a group of meterials prepared by the oblique or the glancing angle deposition technique. They take the form of rods having different shapes such as nanocolumns, nanoscrews, nanozigzags and many other nanoshapes. Their potential for biosensing is highlighted in this review particularly the metallic ones due to their remarkable plasmonic properties. The techniques that have been shown so far to be of high potential are: extended surface plasmon resonance (SPR), localised SPR, surface enhanced flourescence (SEF) and Raman scattering (SERS). The use of metal nSTFs in SPR biosensors with Kretschmann-Raether configuration enhances both the angular and the spectral sensitivities due to the porosity and adds more degrees of freedom in designing evanescent waves based techniques. The metallic nSTFs, exhibit remarkable localised plasmonic properties that make them a promising substrate for enhanced spectroscopies. Their long term stability in water environment makes them suitable candidates for biosensing in water as it is already demonstrated for several water pollutants. The influences of the nanostructures' size, topology, the substrate features, and the preparation conditions on the enhancement of SEF and SERS are highlighted with emphases on the unresolved issues and future trends.

Combining plasmonic and electrochemical biosensing methods.

The idea of combining electrochemical (EC) and plasmonic biosensor methods was introduced almost thirty years ago and the potential of electrochemical-plasmonic (EC-P) biosensors has been highlighted ever since. Despite that, the use of EC-P biosensors in analytics has been rather limited so far and the search for unique applications of the EC-P method continues. In this paper, we review the advances in the field of EC-P biosensors and discuss the features and benefits they can provide. In addition, we identify the main challenges for the development of EC-P biosensors and the limitations that prevent EC-P biosensors from more widespread use. Finally, we review applications of EC-P biosensors for the investigation and quantification of biomolecules, and for the study of biomolecular and cellular processes.

Plasmonic Nanogap-Enhanced Tunable Three-Dimensional Nanoframes in Application to Clinical Diagnosis of Alzheimer's Disease.

Advancements in nanotechnology led to significant improvements in synthesizing plasmon-enhanced nanoarchitectures for biosensor applications, and high-yield productivity at low cost is vital to step further into medical commerce. Metal nanoframes via wet chemistry are gaining attention for their homogeneous structure and outstanding catalytic and optical properties. However, nanoframe morphology should be considered delicately when brought to biosensors to utilize its superior characteristics thoroughly, and the need to prove its clinical applicability still remains. Herein, we controlled the frameworks of double-walled nanoframes (DWFs) precisely via wet chemistry to construct a homogeneous plasmon-enhanced nanotransducer for localized surface plasmon resonance biosensors. By tuning the physical properties considering the finite-difference time-domain simulation results, biomolecular interactions were feasible in the electromagnetic field-enhanced nanospace. As a result, DWF10 exhibited a 10-fold lower detection limit of 2.21 fM compared to DWF14 for tau detection. Further application into blood-based clinical and Alzheimer's disease (AD) diagnostics, notable improvement in classifying mild cognitive impairment patients against healthy controls and AD patients, was demonstrated along with impressive AUC values. Thus, in response to diverse detection methods, optimizing nanoframe dimensions such as nanogap and frame thickness to maximize sensor performance is critical to realize future POCT diagnosis.

Corn-inspired high-density plasmonic metal-organic frameworks microneedles for enhanced SERS detection of acetaminophen.

Effective monitoring of acetaminophen (APAP) dosage is crucial for preventing antipyretic abuse, ensuring therapeutic efficacy, and minimizing toxic effects. However, existing self-monitoring methods are limited. In this study, we designed a plasmonic microneedle (MN) sensor for real-time nondestructive monitoring of acetaminophen levels in dermal interstitial fluid (ISF) by employing a handheld Raman spectrometer. The fabricated MN sensor incorporated a high-density plasmonic MOFs known as HDPM, which unique structure of large specific surface area, specific pore structure as well as high density gold nanospheres packing enabled the excellent performance of selective ISF drug enrichment and surface-enhanced Raman scattering (SERS). The maximum electric field enhancement factor of the HDPM nanostructure could be calculated as 5.73 × 107. The developed HDPM@MNs was characterized with a core-shell type "soft on the outside and rigid on the inside" structure, which exhibited sufficient hardness and flexibility to penetrate the dermal tissue with little damage, and robust SERS enhancement effect in APAP detection without any interfering peaks. Through a hydrogel drug simulation experiment, the sensor demonstrated robust capabilities for acetaminophen enrichment and monitoring, exhibiting excellent stability and repeatability. The quantitative detection window spanned from 1 to 100 µM, with a low detection limit reaching 0.45 µM. Furthermore, by monitoring the concentration of acetaminophen in the interstitial fluid of rat skin at different doses and for different administration times, the HDPM@MNs can be used to determine the pharmacokinetics of acetaminophen in rats and the physiological characteristics associated with various dosage regimens. This work not only holds promise for drug monitoring but also provides a novel approach for nondestructive monitoring of other crucial low-abundance physiological markers.

Distinct plasma phosphorylated-tau proteins profiling for the differential diagnosis of mild cognitive impairment and Alzheimer's disease by plasmonic asymmetric nanobridge-based biosensor.

The differential diagnosis between mild cognitive impairment (MCI) and Alzheimer's disease (AD) has been highly demanded for its effectiveness in preventing and contributing to early diagnosis of AD. To this end, we developed a single plasmonic asymmetric nanobridge (PAN)-based biosensor to differentially diagnose MCI and AD by quantitative profiling of phosphorylated tau proteins (p-tau) in clinical plasma samples, which revealed a significant correlation with AD development and progression. The PAN was designed to have a conductive junction and asymmetric structure, which was unable to be synthesized by the traditional thermodynamical methods. For its unique morphological characteristics, PAN features high electromagnetic field enhancement, enabling the biosensor to achieve high sensitivity, with a limit of detection in the attomolar regime for quantitative analysis of p-tau. By introducing support vector machine (SVM)-based machine learning algorithm, the improved diagnostic system was achieved for prediction of healthy controls, MCI, and AD groups with an accuracy of 94.47 % by detecting various p-tau species levels in human plasma. Thus, our proposed PAN-based plasmonic biosensor has a powerful potential in clinical utility for predicting the onset of AD progression in the asymptomatic phase.

Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic Biosensing.

The development of biomolecular imprinting over the last decade has raised promising perspectives in replacing natural antibodies with artificial antibodies. A significant number of reports have been dedicated to imprinting of organic and inorganic nanostructures, but very few were performed on nanomaterials with a transduction function. Herein we describe a relatively fast and efficient plasmonic hot spot-localized surface imprinting of gold nanorods using reversible template immobilization and siloxane co-polymerization. The technique enables a fine control of the imprinting process at the nanometer scale and provides a nanobiosensor with high selectivity and reusability. Proof of concept is established by the detection of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker for acute kidney injury, using localized surface plasmon resonance spectroscopy. The work represents a valuable step towards plasmonic nanobiosensors with synthetic antibodies for label-free and cost-efficient diagnostic assays. We expect that this novel class of surface imprinted plasmonic nanomaterials will open up new possibilities in advancing biomedical applications of plasmonic nanostructures.

Wearable Plasmonic Sweat Biosensor for Acetaminophen Drug Monitoring.

Monitoring the acetaminophen dosage is important to prevent the occurrence of adverse reactions such as liver failure and kidney damage. Traditional approaches to monitoring acetaminophen dosage mainly rely on invasive blood collection. Herein, we developed a noninvasive microfluidic-based wearable plasmonic sensor to achieve simultaneous sweat sampling and acetaminophen drug monitoring for vital signs. The fabricated sensor employs an Au nanosphere cone array as the key sensing component, which poses a substrate with surface-enhanced Raman scattering (SERS) activity to noninvasively and sensitively detect the fingerprint of acetaminophen molecules based on its unique SERS spectrum. The developed sensor enabled the sensitive detection and quantification of acetaminophen at concentrations as low as 0.13 µM. We further evaluated the sweat sensor integrated with a Raman spectrometer for monitoring acetaminophen in drug-administered subjects. These results indicated that the sweat sensor could measure acetaminophen levels and reflect drug metabolism. The sweat sensors have revolutionized wearable sensing technology by adopting label-free and sensitive molecular tracking methods for noninvasive and point-of-care drug monitoring and management.

Precise profiling of exosomal biomarkers via programmable curved plasmonic nanoarchitecture-based biosensor for clinical diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease of complex pathogenesis, with overt symptoms following disease progression. Early AD diagnosis is challenging due to the lack of robust biomarkers and limited patient access to diagnostics via neuroimaging and cerebrospinal fluid (CSF) tests. Exosomes present in body fluids are attracting attention as diagnostic biomarkers that directly reflect neuropathological features within the brain. In particular, exosomal miRNAs (exomiRs) signatures are involved in AD pathogenesis, showing a different expression between patients and the healthy controls (HCs). However, low yield and high homologous nature impede the accuracy and reproducibility of exosome blood-based AD diagnostics. Here, we developed a programmable curved plasmonic nanoarchitecture-based biosensor to analyze exomiRs in clinical serum samples for accurate AD diagnosis. To allow the detection of exomiRs in serum at attomolar levels, nanospaces (e.g., nanocrevice and nanocavity) were introduced into the nanostructures to dramatically increase the spectral sensitivity by adjusting the bending angle of the plasmonic nanostructure through sodium chloride concentration control. The developed biosensor classifies individuals into AD, mild cognitive impairment (MCI) patients, and HCs through profiling and quantifying exomiRs. Furthermore, integrating analysis expression patterns of multiple exosomal biomarkers improved serum-based diagnostic performance (average accuracy of 98.22%). Therefore, precise, highly sensitive serum-derived exosomal biomarker detection-based plasmonic biosensor has a robust capacity to predict the molecular pathologic of neurodegenerative disease, progression of cognitive decline, MCI/AD conversion, as well as early diagnosis and treatment.

Detection of multiplex exosomal miRNAs for clinically accurate diagnosis of Alzheimer's disease using label-free plasmonic biosensor based on DNA-Assembled advanced plasmonic architecture.

Alzheimer's disease (AD), the most common neurologic disorder, is characterized by progressive cognitive impairment. However, the low clinical significance of the currently used core AD biomarkers amyloid-beta and tau proteins remains a challenge. Recently, exosomes, found in human biological fluids, are gaining increasing attention because of their clinical significance in diagnosing of various diseases. In particular, blood-derived exosomal miRNAs are not only stable but also provide information regarding the different characteristics according to AD progression. However, quantitative and qualitative detection is difficult due to their characteristics, such as small size, low abundance, and high homology. Here, we present a DNA-assembled advanced plasmonic architecture (DAPA)-based plasmonic biosensor to accurately detect exosomal miRNAs in human serum. The designed nanoarchitecture possesses two narrow nanogaps that induce plasmon coupling; this significantly enhances its optical energy density, resulting in a 1.66-fold higher refractive-index (RI) sensitivity than nanorods at localized surface plasmon resonance (LSPR). Thus, the proposed biosensor is ultrasensitive and capable of selective single-nucleotide detection of exosomal miRNAs at the attomolar level. Furthermore, it identified AD patients from healthy controls by measuring the levels of exosomal miRNA-125b, miRNA-15a, and miRNA-361 in clinical serum samples. In particular, the combination of exosomal miRNA-125b and miRNA-361 showed the best diagnostic performance with a sensitivity of 91.67%, selectivity of 95.00%, and accuracy of 99.52%. These results demonstrate that our sensor can be clinically applied for AD diagnosis and has great potential to revolutionize the field of dementia research and treatment in the future.

Exploring near-field sensing efficiency of complementary plasmonic metasurfaces for immunodetection of tumor markers.

Plasmonic metasurface biosensors have great potential on label-free high-throughput clinical detection of human tumor markers. In the past decades, nanopillar and nanohole metasurfaces have become the common choices for plasmonic biosensing, because they typically enable universal simple large-area nanopatterns via a low-cost reproducible fabrication manner. The two kinds of metasurfaces have the complementary shapes and are used to be assumed as the same type of two-dimensional plasmonic nanograting for biosensing. Up to date, there is still a lack of comparison study on their biosensing performance, which is critical to guide their better applications on tumor marker detection. In this study, we compare the bulk/surface refractive index and sensitivity of plasmonic nanopillar (PNP) and plasmonic nanohole (PNH) metasurfaces in order to evaluate their biosensing capabilities. The sensing physics about their space near-field utilization is systematically revealed. The PNH metasurface demonstrates a higher biomolecule sensitivity versus the complementary PNP metasurface, and its limit of detection for bovine serum albumin reaches ∼0.078 ng/mL, which implies a greater potential of detecting cancer biomarkers. We further adopt the PNH metasurfaces for immunoassay of three typical tumor markers by testing clinical human serum samples. The results imply that the immunodetection of alpha-fetoprotein has the most optimal sensing efficiency with the lowest detection concentration (<5 IU/mL), which is much lower than its clinical diagnosis threshold of ∼16.5 IU/mL for medical examination. Our work has not only illuminated the distinct biosensing properties of complementary metasurfaces, but also provided a promising way to boost plasmonic biosensing for point-of-care testing.

Flexible Plasmonic Biosensors for Healthcare Monitoring: Progress and Prospects.

The noble metal nanoparticle has been widely utilized as a plasmonic unit to enhance biosensors, by leveraging its electric and/or optical properties. Integrated with the "flexible" feature, it further enables opportunities in developing healthcare products in a conformal and adaptive fashion, such as wrist pulse tracers, body temperature trackers, blood glucose monitors, etc. In this work, we present a holistic review of the recent advance of flexible plasmonic biosensors for the healthcare sector. The technical spectrum broadly covers the design and selection of a flexible substrate, the process to integrate flexible and plasmonic units, the exploration of different types of flexible plasmonic biosensors to monitor human temperature, blood glucose, ions, gas, and motion indicators, as well as their applications for surface-enhanced Raman scattering (SERS) and colorimetric detections. Their fundamental working principles and structural innovations are scoped and summarized. The challenges and prospects are articulated regarding the critical importance for continued progress of flexible plasmonic biosensors to improve living quality.

Functionalized terahertz plasmonic metasensors: Femtomolar-level detection of SARS-CoV-2 spike proteins.

Effective and efficient management of human betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 virus infection i.e., COVID-19 pandemic, required sensitive and selective sensors with short sample-to-result durations for performing desired diagnostics. In this direction, one appropriate alternative approach to detect SARS-CoV-2 virus protein at low level i.e., femtomolar (fM) is exploring plasmonic metasensor technology for COVID-19 diagnostics, which offers exquisite opportunities in advanced healthcare programs, and modern clinical diagnostics. The intrinsic merits of plasmonic metasensors stem from their capability to squeeze electromagnetic fields, simultaneously in frequency, time, and space. However, the detection of low-molecular weight biomolecules at low densities is a typical drawback of conventional metasensors that has recently been addressed using toroidal metasurface technology. This research is focused on the fabrication of a miniaturized plasmonic immunosensor based on toroidal electrodynamics concept that can sustain robustly confined plasmonic modes with ultranarrow lineshapes in the terahertz (THz) frequencies. By exciting toroidal dipole mode using our quasi-infinite metasurface and a judiciously optimized protocol based on functionalized gold nanoparticles (AuNPs) conjugated with the specific monoclonal antibody specific to spike protein (S1) of SARS-CoV-2 virus onto the metasurface, the resonance shifts for diverse concentrations of the spike protein are monitored. Possessing molecular weight around ~76 kDa allowed to detect the presence of SARS-CoV-2 virus protein with significantly low as limit of detection (LoD) was achieved as ~4.2 fM. We envisage that outcomes of this research will pave the way toward the use of toroidal metasensors as practical technologies for rapid and precise screening of SARS-CoV-2 virus carriers, symptomatic or asymptomatic, and spike proteins in hospitals, clinics, laboratories, and site of infection.

The role of biosensors in coronavirus disease-2019 outbreak.

Herein, we have summarized and argued about biomarkers and indicators used for the detection of severe acute respiratory syndrome coronavirus 2. Antibody detection methods are not considered suitable to screen individuals at early stages and asymptomatic cases. The diagnosis of coronavirus disease 2019 using biomarkers and indicators at point-of-care level is much crucial. Therefore, it is urgently needed to develop rapid and sensitive detection methods which can target antigens. We have critically elaborated key role of biosensors to cope the outbreak situation. In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor, and surface plasmon resonance biosensors in the detection of severe acute respiratory syndrome coronavirus 2 has been underscored. Finally, we have outlined pros and cons of diagnostic approaches and future directions.

Entangled Nanoplasmonic Cavities for Estimating Thickness of Surface-Adsorbed Layers.

Plasmonic sensors provide real-time and label-free detection of biotargets with unprecedented sensitivity and detection limit. However, they usually lack the ability to estimate the thickness of the target layer formed on top of the sensing surface. Here, we report a sensing modality based on reflection spectroscopy of a nanoplasmonic Fabry-Perot cavity array, which exhibits characteristics of both surface plasmon polaritons and localized plasmon resonances and outperforms its conventional counterparts by providing the thickness of the surface-adsorbed layers. Through numerical simulations, we demonstrate that the designed plasmonic surface resembles two entangled Fabry-Perot cavities excited from both ends. Performance of the device is evaluated by studying sensor response in the refractive index (RI) measurement of aqueous glycerol solutions and during formation of a surface-adsorbed layer consisting of protein (i.e., NeutrAvidin) molecules. By tracking the resonance wavelengths of the two modes of the nanoplasmonic surface, it is therefore possible to measure the thickness of a homogeneous adsorbed layer and RI of the background solution with precisions better than 4 nm and 0.0001 RI units. Using numerical simulations, we show that the thickness estimation algorithm can be extended for layers consisting of nanometric analytes adsorbed on an antibody-coated sensor surface. Furthermore, performance of the device has been evaluated to detect exosomes. By providing a thickness estimation for adsorbed layers and differentiating binding events from background RI variations, this device can potentially supersede conventional plasmonic sensors.

Nanohole array plasmonic biosensors: Emerging point-of-care applications.

Point-of-care (POC) applications have expanded hugely in recent years and is likely to continue, with an aim to deliver cheap, portable, and reliable devices to meet the demands of healthcare industry. POC devices are designed, prototyped, and assembled using numerous strategies but the key essential features that biosensing devices require are: (1) sensitivity, (2) selectivity, (3) specificity, (4) repeatability, and (5) good limit of detection. Overall the fabrication and commercialization of the nanohole array (NHA) setup to the outside world still remains a challenge. Here, we review the various methods of NHA fabrication, the design criteria, the geometrical features, the effects of surface plasmon resonance (SPR) on sensing as well as current state-of-the-art of existing NHA sensors. This review also provides easy-to-understand examples of NHA-based POC biosensing applications, its current status, challenges, and future prospects.

Plasmonic Biosensor Based on Vertical Arrays of Gold Nanoantennas.

Implementing large arrays of gold nanowires as functional elements of a plasmonic biosensor is an important task for future medical diagnostic applications. Here we present a microfluidic-channel-integrated sensor for the label-free detection of biomolecules, relying on localized surface plasmon resonances. Large arrays (∼1 cm2) of vertically aligned and densely packed gold nanorods to receive, locally confine, and amplify the external optical signal are used to allow for reliable biosensing. We accomplish this by monitoring the change of the optical nanostructure resonance in the presence of biomolecules within the tight focus area above the nanoantennas, combined with a surface treatment of the nanowires for a specific binding of the target molecules. As a first application, we detect the binding kinetics of two distinct DNA strands as well as the following hybridization of two complementary strands (cDNA) with different lengths (25 and 100 bp). Upon immobilization, a redshift of 1 nm was detected; further backfilling and hybridization led to a peak shift of additional 2 and 5 nm for 25 and 100 bp, respectively. We believe that this work gives deeper insight into the functional understanding and technical implementation of a large array of gold nanowires for future medical applications.

Phase-sensitive plasmonic biosensor using a portable and large field-of-view interferometric microarray imager.

Nanophotonics, and more specifically plasmonics, provides a rich toolbox for biomolecular sensing, since the engineered metasurfaces can enhance light-matter interactions to unprecedented levels. So far, biosensing associated with high-quality factor plasmonic resonances has almost exclusively relied on detection of spectral shifts and their associated intensity changes. However, the phase response of the plasmonic resonances have rarely been exploited, mainly because this requires a more sophisticated optical arrangement. Here we present a new phase-sensitive platform for high-throughput and label-free biosensing enhanced by plasmonics. It employs specifically designed Au nanohole arrays and a large field-of-view interferometric lens-free imaging reader operating in a collinear optical path configuration. This unique combination allows the detection of atomically thin (angstrom-level) topographical features over large areas, enabling simultaneous reading of thousands of microarray elements. As the plasmonic chips are fabricated using scalable techniques and the imaging reader is built with low-cost off-the-shelf consumer electronic and optical components, the proposed platform is ideal for point-of-care ultrasensitive biomarker detection from small sample volumes. Our research opens new horizons for on-site disease diagnostics and remote health monitoring.