A Biomimetic Plasmonic Nanoreactor for Reliable Metabolite Detection

Abstract

and the concomitant elevation of lactate in the interstitial fluids due to the enhanced glycolysis energy metabolism. [1] Accurate profiling of medically relevant metabolites in human body fluids provides molecular information for deep understanding of pathological mechanism at a more distal level than genomic analysis, and enables precise diagnosis and treatment of the underling diseases. [2] Till now, different advanced techniques, including magnetic resonance spectroscopy, [3] mass spectrometry, [4] and chromatography coupled mass spectroscopy, [5] have been developed to measure metabolites in vitro and in vivo. While useful, these techniques require sophisticated and expensive equipment, hampering their use in rapid point-ofcare clinical testing. By contrast, enzymebased bioassays, where the presence of analytes is optically or electrochemically detected through the highly specific and efficient enzymatic reaction, provide novel opportunities for detection metabolite biomarkers. [6] These approaches show enough figures of merits regarding device portability, speed, sample consumption and cost. However, the inherent instability of enzyme at elevated temperature, in circumstance containing digestive enzymes or chemical chelates, and when storing the enzyme long-term represents a longstanding yet largely unsolved challenge that leads to poor reproducibility and accuracy in enzyme-based metabolite analysis. [7] Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long-term management of various diseases. Although widely used, existing enzymatic metabolite assays face challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/ nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all-in-one bio-nanoreactors is reported herein foruse in surface-enhanced Raman scattering (SERS)-based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long-time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by-product H 2 O 2 , enabling sensitive metabolite quantification in a "sample in and answer out" manner. The nanoreactor makes any oxidoreductase-responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing.

Machine learning of serum metabolic patterns encodes early-stage lung adenocarcinoma

“…Metabolic serum analysis is more distal over genomic and proteomic approaches for precision diagnostics 11 – 13 , but it has rarely been reported or studied for complex diseases such as LA, due to the lack of efficient metabolite detection tools and systematically designed patient sub-groups. Changes in metabolism are associated with diverse diseases including LA 6 , 14 . Specifically, malignant transformations are associated with altered metabolic pathways for biosynthetic and bioenergetic processes, which depict an adjustment in blood metabolomics.…”

Novel Clinimetric Toolset to Quantify the Stability of Blood Pressure and Its Application to Evaluate Cardiovascular Function After Spinal Cord Injury

“…The proposed method also has implications beyond blood pressure analysis. With the rapid development of wearable sensors (Zhang et al, 2019;Moonen et al, 2020) and point of care tests (Huang et al, 2019;Liu et al, 2020;Xu et al, 2020) as well as the advancements in neuromodulation and pharmaceutical interventions, the applications of modulating various biomarkers to fall into clinically accepted ranges are often desired. Therefore, the utilization of the methodology proposed in this study can be expanded into these other areas.…”

Ultra‐Fast Label‐Free Serum Metabolic Diagnosis of Coronary Heart Disease via a Deep Stabilizer

“…[ 2 ] Compared to the traditional analytical approaches (e.g., nuclear magnetic resonance (NMR) and biochemical methods), mass spectrometry (MS) demonstrates advantages of molecular identification capability and high analytical speed. Conventionally, NMR [ 3 ] measures atomic species by their electromagnetic response from specific atoms in the interaction with magnetic fields and biochemical methods [ 4 ] require enzymes or antibodies for targeted molecular recognition based selective reaction, [ 4 , 5 ] both of which usually need relatively long detection time due to the relaxation or recognition/reaction. For comparison, MS can directly record the mass‐to‐charge ratio (m/z) of molecules and their fragments, affording enhanced molecular identification capability and high analytical speed.…”