scispace - formally typeset
Search or ask a question
Author

Lin Huang

Other affiliations: Fudan University
Bio: Lin Huang is an academic researcher from Shanghai Jiao Tong University. The author has contributed to research in topics: Medicine & Cognition. The author has an hindex of 18, co-authored 49 publications receiving 890 citations. Previous affiliations of Lin Huang include Fudan University.

Papers published on a yearly basis

Papers
More filters
Journal ArticleDOI
TL;DR: A silver nanoparticle plasmonics approach is used for the detection of biomarkers in patients as well as investigate the distribution of drugs in serum and cerebral spinal fluid.
Abstract: In-vitro metabolite and drug detection rely on designed materials-based analytical platforms, which are universally used in biomedical research and clinical practice. However, metabolic analysis in bio-samples needs tedious sample preparation, due to the sample complexity and low molecular abundance. A further challenge is to construct diagnostic tools. Herein, we developed a platform using silver nanoshells. We synthesized SiO2@Ag with tunable shell structures by multi-cycled silver mirror reactions. Optimized nanoshells achieved direct laser desorption/ionization mass spectrometry in 0.5 μL of bio-fluids. We applied these nanoshells for disease diagnosis and therapeutic evaluation. We identified patients with postoperative brain infection through daily monitoring and glucose quantitation in cerebrospinal fluid. We measured drug distribution in blood and cerebrospinal fluid systems and validated the function of blood-brain/cerebrospinal fluid-barriers for pharmacokinetics. Our work sheds light on the design of materials for advanced metabolic analysis and precision diagnostics. Preparation of samples for diagnosis can affect the detection of biomarkers and metabolites. Here, the authors use a silver nanoparticle plasmonics approach for the detection of biomarkers in patients as well as investigate the distribution of drugs in serum and cerebral spinal fluid.

141 citations

Journal ArticleDOI
TL;DR: A technique to analyse serum metabolites and define a biomarker panel for early-stage lung adenocarcinoma diagnosis is developed and holds promise as an efficient test for low-cost rollout to clinics.
Abstract: Early cancer detection greatly increases the chances for successful treatment, but available diagnostics for some tumours, including lung adenocarcinoma (LA), are limited. An ideal early-stage diagnosis of LA for large-scale clinical use must address quick detection, low invasiveness, and high performance. Here, we conduct machine learning of serum metabolic patterns to detect early-stage LA. We extract direct metabolic patterns by the optimized ferric particle-assisted laser desorption/ionization mass spectrometry within 1 s using only 50 nL of serum. We define a metabolic range of 100–400 Da with 143 m/z features. We diagnose early-stage LA with sensitivity~70–90% and specificity~90–93% through the sparse regression machine learning of patterns. We identify a biomarker panel of seven metabolites and relevant pathways to distinguish early-stage LA from controls (p < 0.05). Our approach advances the design of metabolic analysis for early cancer detection and holds promise as an efficient test for low-cost rollout to clinics. Early diagnosis significantly improves the probability of successful cancer therapy. Here, the authors develop a technique to analyse serum metabolites and define a biomarker panel for early-stage lung adenocarcinoma diagnosis.

113 citations

Journal ArticleDOI
TL;DR: A novel plasmonic chip for clinical metabolic fingerprinting is developed and on-chip in vitro metabolic diagnosis of early stage lung cancer patients using serum and exosomes is demonstrated for the first time.
Abstract: Current metabolic analysis is far from ideal to engage clinics and needs rationally designed materials and device. Here we developed a novel plasmonic chip for clinical metabolic fingerprinting. We first constructed a series of chips with gold nanoshells on the surface through controlled particle synthesis, dip-coating, and gold sputtering for mass production. We integrated the optimized chip with microarrays for laboratory automation and micro-/nanoscaled experiments, which afforded direct high-performance metabolic fingerprinting by laser desorption/ionization mass spectrometry using 500 nL of various biofluids and exosomes. Further we for the first time demonstrated on-chip in vitro metabolic diagnosis of early stage lung cancer patients using serum and exosomes. This work initiates a new bionanotechnology based platform for advanced metabolic analysis toward large-scale diagnostic use.

100 citations

Journal ArticleDOI
TL;DR: This unique approach couples the immunomagnetic separation of C TCs and LDI‐MS based metabolic analysis, which represents a key step forward for downstream metabolites analysis of rare cells to investigate the biological features of CTCs and their cellular responses in both pathological and physiological phenomena.
Abstract: We for the first time demonstrate multi-functional magnetic particles based rare cell isolation combined with the downstream laser desorption/ionization mass spectrometry (LDI-MS) to measure the metabolism of enriched circulating tumor cells (CTCs). The characterization of CTCs metabolism plays a significant role in understanding the tumor microenvironment, through exploring the diverse cellular process. However, characterizing cell metabolism is still challenging due to the low detection sensitivity, high sample complexity, and tedious preparation procedures, particularly for rare cells analysis in clinical study. Here we conjugate ferric oxide magnetic particles with anti-EpCAM on the surface for specific, efficient enrichment of CTCs from PBS and whole blood with cells concentration of 6-100 cells per mL. Moreover, these hydrophilic particles as matrix enable sensitive and selective LDI-MS detection of small metabolites (MW<500 Da) in complex bio-mixtures and can be further coupled with isotopic quantification to monitor selected molecules metabolism of ~50 CTCs. Our unique approach couples the immunomagnetic separation of CTCs and LDI-MS based metabolic analysis, which represents a key step forward for downstream metabolites analysis of rare cells to investigate the biological features of CTCs and their cellular responses in both pathological and physiological phenomena.

95 citations

Journal ArticleDOI
TL;DR: Pd–Au synthetic alloys are reported for mass‐spectrometry‐based metabolic fingerprinting and analysis, toward medulloblastoma diagnosis and radiotherapy evaluation and will lead to the application‐driven development of novel materials with tailored structural design and establishment of new protocols for precision medicine in near future.
Abstract: Diagnostics is the key in screening and treatment of cancer. As an emerging tool in precision medicine, metabolic analysis detects end products of pathways, and thus is more distal than proteomic/genetic analysis. However, metabolic analysis is far from ideal in clinical diagnosis due to the sample complexity and metabolite abundance in patient specimens. A further challenge is real-time and accurate tracking of treatment effect, e.g., radiotherapy. Here, Pd-Au synthetic alloys are reported for mass-spectrometry-based metabolic fingerprinting and analysis, toward medulloblastoma diagnosis and radiotherapy evaluation. A core-shell structure is designed using magnetic core particles to support Pd-Au alloys on the surface. Optimized synthetic alloys enhance the laser desorption/ionization efficacy and achieve direct detection of 100 nL of biofluids in seconds. Medulloblastoma patients are differentiated from healthy controls with average diagnostic sensitivity of 94.0%, specificity of 85.7%, and accuracy of 89.9%, by machine learning of metabolic fingerprinting. Furthermore, the radiotherapy process of patients is monitored and a preliminary panel of serum metabolite biomarkers is identified with gradual changes. This work will lead to the application-driven development of novel materials with tailored structural design and establishment of new protocols for precision medicine in near future.

91 citations


Cited by
More filters
Journal Article
TL;DR: Wang et al. as discussed by the authors described the single cell analysis as the new frontier in Omics, and single cell Omics has the potential to transform systems biology through new discoveries derived from cellular heterogeneity.
Abstract: Single cell analysis: the new frontier in ‘Omics’ Daojing Wang 1 and Steven Bodovitz 2 1. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 2. BioPerspectives, San Francisco, CA Corresponding author: Wang, D. (djwang@lbl.gov) Cellular heterogeneity arising from stochastic expression of genes, proteins, and metabolites is a fundamental principle of cell biology, but single cell analysis has been beyond the capabilities of ‘Omics’ technologies. This is rapidly changing with the recent examples of single cell genomics, transcriptomics, proteomics, and metabolomics. The rate of change is expected to accelerate owing to emerging technologies that range from micro/nanofluidics to microfabricated interfaces for mass spectrometry to third- and fourth-generation automated DNA sequencers. As described in this review, single cell analysis is the new frontier in Omics, and single cell Omics has the potential to transform systems biology through new discoveries derived from cellular heterogeneity. Single cell analysis: needs and applications Cellular heterogeneity Cellular heterogeneity within an isogenic cell population is a widespread event [1, 2]. Stochastic gene and protein expression at the single cell level has been clearly demonstrated in different systems using a variety of techniques [3-5]. Therefore, analyzing cell ensembles individually with high spatiotemporal resolutions will lead to a

526 citations

01 Mar 2014
TL;DR: A continuous-flow culture apparatus for maintaining proliferating cells in low-nutrient media for long periods of time is developed and used to undertake competitive proliferation assays, concluding that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.
Abstract: As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

493 citations

Journal ArticleDOI
TL;DR: A broad overview of aptamer-based liquid biopsy techniques for precision medicine can be found in this article, where the authors present a summary of state-of-the-art strategies for multivalent aptamer assembly and aptamer interface modification.
Abstract: The past decade has witnessed ongoing progress in precision medicine to improve human health. As an emerging diagnostic technique, liquid biopsy can provide real-time, comprehensive, dynamic physiological and pathological information in a noninvasive manner, opening a new window for precision medicine. Liquid biopsy depends on the sensitive and reliable detection of circulating targets (e.g., cells, extracellular vesicles, proteins, microRNAs) from body fluids, the performance of which is largely governed by recognition ligands. Aptamers are single-stranded functional oligonucleotides, capable of folding into unique tertiary structures to bind to their targets with superior specificity and affinity. Their mature evolution procedure, facile modification, and affinity regulation, as well as versatile structural design and engineering, make aptamers ideal recognition ligands for liquid biopsy. In this review, we present a broad overview of aptamer-based liquid biopsy techniques for precision medicine. We begin with recent advances in aptamer selection, followed by a summary of state-of-the-art strategies for multivalent aptamer assembly and aptamer interface modification. We will further describe aptamer-based micro-/nanoisolation platforms, aptamer-enabled release methods, and aptamer-assisted signal amplification and detection strategies. Finally, we present our perspectives regarding the opportunities and challenges of aptamer-based liquid biopsy for precision medicine.

187 citations

Journal ArticleDOI
01 Sep 2019
TL;DR: This review briefly introduces the structures, composition, and properties of Janus particles, followed by a summary of their biomedical applications, and explores the synthetic methodologies ofJanus particles.
Abstract: Janus particles with an anisotropic structure have emerged as a focus of intensive research due to their diverse composition and surface chemistry, which show excellent performance in various fields, especially in biomedical applications. In this review, we briefly introduce the structures, composition, and properties of Janus particles, followed by a summary of their biomedical applications. Then we review several design strategies including morphology, particle size, composition, and surface modification, that will affect the performance of Janus particles. Subsequently, we explore the synthetic methodologies of Janus particles, with an emphasis on the most prevalent synthetic method (surface nucleation and seeded growth). Following this, we highlight Janus particles in biomedical applications, especially in drug delivery, bio-imaging, and bio-sensing. Finally, we will consider the current challenges the materials face with perspectives in the future directions.

164 citations