Featured
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Review Article
| Open Access
Artificial cells for in vivo biomedical applications through red blood cell biomimicry
Despite the enormous progress in the field of giant lipid vesicles, their use for in vivo biomedical applications is limited. Here, the authors discuss red blood cells as inspiration for enhancing those vesicles, investigating the required cellular features and the corresponding technical hurdles.
- Jorik Waeterschoot
- , Willemien Gosselé
- & Xavier Casadevall i Solvas
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Article
| Open Access
Lanthanide luminescence nanothermometer with working wavelength beyond 1500 nm for cerebrovascular temperature imaging in vivo
The strong scattering of biological tissue causes challenges when monitoring temperature changes at the microscale. Here, the authors propose a nanothermometer based on lanthanide luminescence, enabling minimally invasive imaging of the cerebrovascular system of mice at nearly 200 μm resolution.
- Yukai Wu
- , Fang Li
- & Xingjun Zhu
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Article
| Open Access
Identifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer. Here, authors develop a dual endogenous reporter system to identify functional regulators of aberrant stem cell and differentiation programs, showing that SMARCB1 restricts differentiation, and nominating other regulators with therapeutic potential.
- Sandor Spisak
- , David Chen
- & Nilay S. Sethi
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Article
| Open Access
Biporous silica nanostructure-induced nanovortex in microfluidics for nucleic acid enrichment, isolation, and PCR-free detection
Efficient enrichment and isolation of pathogens are crucial for accurate and sensitive disease identification. Here, the authors present a chip equipped with biporous nanofilms that induces a nanovetex in a microfluidic channel for nucleic acid enrichment, isolation, and detection.
- Eunyoung Jeon
- , Bonhan Koo
- & Joonseok Lee
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Article
| Open Access
Micrometer-thick and porous nanocomposite coating for electrochemical sensors with exceptional antifouling and electroconducting properties
It is vital but challenging to develop coating technologies for addressing reliability and durability issues of electrochemical sensors when exposed to diverse and complex biological environments. Here, the authors report a micrometer-thick, porous and robust nanocomposite coating that enables highly sensitive and stable electrochemical sensors.
- Jeong-Chan Lee
- , Su Yeong Kim
- & Donald E. Ingber
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Article
| Open Access
Rapid and visual identification of β-lactamase subtypes for precision antibiotic therapy
The rapid identification of drug-resistant bacteria is vital for effective treatment and to avoid antibiotic misuse. Here authors report a paper-based sensor which utilises chromogenic carbapenem and cephalosporin substrates for the identification and discrimination of β-lactamase subtypes.
- Wenshuai Li
- , Jingqi Li
- & Dingbin Liu
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Article
| Open Access
DNA mechanocapsules for programmable piconewton responsive drug delivery
The mechanical dysregulation of cells is associated with several diseases and strategies to deliver drugs based on the “mechanical phenotype” of a cell are desirable. Here, the authors design and characterize DNA mechanocapsules comprised of DNA tetrahedrons that are force responsive, and showed they can encapsulate macromolecular cargo and release it upon application of force.
- Arventh Velusamy
- , Radhika Sharma
- & Khalid Salaita
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Article
| Open Access
Interindividual- and blood-correlated sweat phenylalanine multimodal analytical biochips for tracking exercise metabolism
The in-depth study on the sweat–blood partitioning mechanisms of amino acids is promising for noninvasive metabolic monitoring. Here, the authors develop a wearable biochip for sweat phenylalanine multimodal analysis aimed at tracking exercise metabolic risk and exploring the sweat–blood correlation.
- Bowen Zhong
- , Xiaokun Qin
- & Lili Wang
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Comment
| Open Access
From lab to life: how wearable devices can improve health equity
Wearable devices can provide personalised medicine at the point of need, potentially increasing access to health services and therefore improving health equity. Here the authors discuss their experiences developing wearable devices for vulnerable patient populations, including neonates and pregnant individuals.
- Jessica R. Walter
- , Shuai Xu
- & John A. Rogers
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Article
| Open Access
Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer’s disease from tear fluid
Accurate diagnosis of Alzheimer’s disease in its earliest stage can prevent the disease and delay the symptoms. Here the authors identify a potential Alzheimer’s biomarker from tear fluid, and develop a nanoparticle-based immunoassay for its detection, demonstrating potential in Alzheimer’s diagnosis.
- Sojeong Lee
- , Eunjung Kim
- & Seungjoo Haam
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Article
| Open Access
ANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria
Antibiotic-resistant bacteria pose a growing threat to global health. Here, the authors present an artificial nucleic acid circuit with argonaute protein (ANCA) for one-step, amplification-free, and isothermal detection of carbapenemase-producing Klebsiella pneumoniae.
- Hyowon Jang
- , Jayeon Song
- & Taejoon Kang
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Article
| Open Access
In vivo imaging of mitochondrial DNA mutations using an integrated nano Cas12a sensor
Mutations in mitochondrial DNA (mtDNA) play critical roles in human diseases. Here, the authors describe an integrated Cas12a sensor for sensing mtDNA mutations in vivo, showing potential for diagnostic and therapeutic purposes.
- Yanan Li
- , Yonghua Wu
- & Kaixiang Zhang
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Article
| Open Access
Imaging cellular forces with photonic crystals
Current techniques for visualizing cell generated forces suffer from throughput limitations. Here, Gu et al. introduced photonic crystal cellular force microscopy, inspired by chameleons, enabling visualization and quantification of vertically directed cell forces, well-suited for drug screening.
- Qiwei Li
- , Zaozao Chen
- & Zhongze Gu
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Article
| Open Access
Bioinspired porous three-coordinated single-atom Fe nanozyme with oxidase-like activity for tumor visual identification via glutathione
It is needed yet difficult to achieve a strategy for synthesizing single-atom nanozymes that integrate atomic metal dispersion, elevated mass transport and tailorable coordination environment. Here, the authors address this issue by developing a biomimetic synthetic strategy and demonstrate the application of the resultant single-atom Fe nanozymes for tumor visual identification.
- Da Chen
- , Zhaoming Xia
- & Yongquan Qu
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Article
| Open Access
Tunable Tamm plasmon cavity as a scalable biosensing platform for surface enhanced resonance Raman spectroscopy
The researchers present a scalable Tamm plasmon cavity using phase change material with large resonance tunability and demonstrated tunable SERS by matching the plasmonic resonance with the molecule absorption for sensitivity enhanced biosensing.
- Kandammathe Valiyaveedu Sreekanth
- , Jayakumar Perumal
- & Jinghua Teng
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Article
| Open Access
Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
l-Lactate is increasingly recognized as a key metabolite and signalling molecule in mammals, but the methods to investigate it in vivo have been limited. Here, authors report a pair of improved biosensors—one green and one red—for visualizing l-lactate both inside and outside of cells.
- Yusuke Nasu
- , Abhi Aggarwal
- & Robert E. Campbell
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Article
| Open Access
Visualization of accessible cholesterol using a GRAM domain-based biosensor
Regulated cholesterol transport is essential for the maintenance of cellular cholesterol distribution and homeostasis, but tools to monitor this process are limited. Here, the authors develop a genetically encoded cholesterol biosensor and demonstrate its use for visualising cellular cholesterol distribution in various live cells in real time.
- Dylan Hong Zheng Koh
- , Tomoki Naito
- & Yasunori Saheki
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Article
| Open Access
Visualizing single-molecule conformational transition and binding dynamics of intrinsically disordered proteins
Intrinsically disordered proteins (IDPs) are highly dynamic and play pivotal roles in cellular processes but can be difficult to study. Here, the authors develop a single-molecule nanocircuit for the real-time monitoring of c-Myc conformational transitions and their interaction with ligands.
- Wenzhe Liu
- , Limin Chen
- & Xuefeng Guo
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Article
| Open Access
In situ synthesis and dynamic simulation of molecularly imprinted polymeric nanoparticles on a micro-reactor system
Molecularly imprinted polymers are useful elements in sensing and biomedical research but their fabrication is challenging. Here, the authors report a micro-reactor for in situ and continuous production of molecularly imprinted polymers.
- Özgecan Erdem
- , Ismail Eş
- & Fatih Inci
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Article
| Open Access
A genetically encoded sensor for visualizing leukotriene B4 gradients in vivo
Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving leukocyte migration and neutrophil swarming, but methods for its real-time detection are lacking. Here, the authors develop GEM-LTB4, a genetically encoded fluorescent biosensor, and use it to visualize leukocyte-derived LTB4 gradients.
- Szimonetta Xénia Tamás
- , Benoit Thomas Roux
- & Balázs Enyedi
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Article
| Open Access
Rapid genetic screening with high quality factor metasurfaces
The authors present a high quality factor metasurface that enables sensitive and highly-parallelized detection of biomolecules. Amplification-free detection of gene fragments down to femtomolar levels is demonstrated within 5 minutes, for rapid nucleic acid analysis.
- Jack Hu
- , Fareeha Safir
- & Jennifer A. Dionne
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Article
| Open Access
Precise in-field molecular diagnostics of crop diseases by smartphone-based mutation-resolved pathogenic RNA analysis
On-site crop disease diagnostics is critical for precise application of pesticides. Here, the authors report an in-field molecular diagnostic tool for wheat pathogens using a nucleic acid amplification-free, gene mutation-resolved and smartphone-integrated genetic assay.
- Ting Zhang
- , Qingdong Zeng
- & Ruijie Deng
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Article
| Open Access
Extending the dynamic range of biomarker quantification through molecular equalization
The human plasma proteome spans over 10 orders of magnitude, but current quantification methods cover only 3-4 orders. Here, authors propose a tuning approach for proximity-based assays, enabling simultaneous quantification of four analytes across a wide concentration range (low fM to mid-nM).
- Sharon S. Newman
- , Brandon D. Wilson
- & H. Tom Soh
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Article
| Open Access
Real-time environmental surveillance of SARS-CoV-2 aerosols
Rapid detection of respiratory pathogens circulating in indoor environments could facilitate improved infection prevention responses. In this proof-of-concept study, the authors develop a pathogen air quality monitor for real-time direct detection of SARS-CoV-2 aerosols and demonstrate its application in rooms of people with SARS-CoV-2 infections.
- Joseph V. Puthussery
- , Dishit P. Ghumra
- & Rajan K. Chakrabarty
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Article
| Open Access
Ratiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN
MAM Ca2+ dynamics play an important role in diverse biological processes, but directly and specifically measuring Ca2+ concentrations in this region is technically challenging. Here the authors report a MAM-specific BRET-based Ca2+ indicator called MAM-Calflux, which works as both a Ca2+ indicator and a structural marker due to its ratiometric nature.
- Eunbyul Cho
- , Youngsik Woo
- & Sang Ki Park
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Article
| Open Access
Intracellular RNA and DNA tracking by uridine-rich internal loop tagging with fluorogenic bPNA
Commonly used protein-based tools to monitor intracellular RNA and DNA can impact steric accessibility and native nucleic acid biology. Here, the authors show that fluorogenic uridine-rich internal loop tagging bPNA probes can be used to label nucleic acids in fixed and live cells.
- Yufeng Liang
- , Sydney Willey
- & Dennis Bong
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Article
| Open Access
A smart pathogen detector engineered from intracellular hydrogelation of DNA-decorated macrophages
Macrophages have the inherent capacity to recognise pathogenic microorganisms, highlighting their potential to be used in biosensing applications. Herein, the authors report a method to transform normally fragile macrophages into robust gelated cell particles for efficient bacterial capture and detection.
- Yueyue Gui
- , Yujing Zeng
- & Chao Li
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Article
| Open Access
RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes
Mechanical forces drive critical cellular processes, but methods to study such cellular forces are typically low-throughput. Here the authors present a method using “Rupture And Deliver” Tension Gauge Tethers, where flow cytometry or sequencing can be used to record the mechanical history of thousands of individual cells.
- Matthew R. Pawlak
- , Adam T. Smiley
- & Wendy R. Gordon
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Article
| Open Access
Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancers
Early detection of multiple cancers through a single method could be clinically important. Here the authors report the diagnostic performance for early detection for multiple cancers using surface-enhanced Raman spectroscopy (SERS) profiles of exosomes from a single blood test and artificial intelligence in a retrospective study design.
- Hyunku Shin
- , Byeong Hyeon Choi
- & Yeonho Choi
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Article
| Open Access
A generalizable nanopore sensor for highly specific protein detection at single-molecule precision
Sensitive and accurate approaches for protein detection have many potential applications. Here the authors show how engineered protein nanopore sensors, consisting of a monobody fused to a single-polypeptide nanopore, can be used for highly specific detection of proteins in complex biofluids.
- Mohammad Ahmad
- , Jeung-Hoi Ha
- & Liviu Movileanu
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Article
| Open Access
Direct digital sensing of protein biomarkers in solution
There are limitations with current protein sensing methods. Here the authors report DigitISA, a digital immunosensor assay based on microchip electrophoretic separation and single-molecule detection that enables quantitation of protein biomarkers in a single, solution-phase step.
- Georg Krainer
- , Kadi L. Saar
- & Tuomas P. J. Knowles
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Article
| Open Access
A supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine
Sensing small biomolecules in biofluids using host-guest chemosensors remains challenging, in part due to the impact of interfering components. Here, the authors develop a dual-macrocyclic rotaxane for tryptophan detection which can function in biofluids such as human serum and urine.
- Joana Krämer
- , Laura M. Grimm
- & Frank Biedermann
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Article
| Open Access
Differential sensing with arrays of de novo designed peptide assemblies
Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.
- William M. Dawson
- , Kathryn L. Shelley
- & Derek N. Woolfson
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Article
| Open Access
Harnessing gut microbes for glycan detection and quantification
Detecting distinct glycans within heterogeneous mixtures is hindered by glycan structural complexity and diversity. Here the authors exploit the ability of gut microbes to sense different glycan structures in order to develop quantitative glycan biosensors by coupling bacterial detection machinery to an optimised luciferase reporter.
- Jennifer L. Modesto
- , Victoria H. Pearce
- & Guy E. Townsend II
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Article
| Open Access
Natural oxidase-mimicking copper-organic frameworks for targeted identification of ascorbate in sensitive sweat sensing
Sweat sensors are important in personalized healthcare using natural oxidase to target biomolecules but these reactions are susceptible to external interference. Here, the authors report tryptophan- and histidine-treated copper metal-organic frameworks which show highly selective activity for ascorbate oxidation and can serve as an efficient ascorbate oxidase-mimicking material in sensitive sweat sensors.
- Zhengyun Wang
- , Yuchen Huang
- & Bao Yu Xia
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Article
| Open Access
Ultrasensitive rapid cytokine sensors based on asymmetric geometry two-dimensional MoS2 diodes
Detection of cytokine biomarkers has the potential to aid in diagnosis and treatment of different diseases. Here, the authors report on the creation of an asymmetric geometry MoS2 diode-based biosensor for the detection of TNF-α as a model biomarker in a proof of concept study.
- Thushani De Silva
- , Mirette Fawzy
- & Michael M. Adachi
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Article
| Open Access
A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites
Metabolic dynamics within the small intestine are difficult to study due to the lack of in situ access. Here, the authors report an ingestible, self-powered, and wireless biosensing system, demonstrating proof-of-principle real-time glucose monitoring in the small intestines of pigs.
- Ernesto De la Paz
- , Nikhil Harsha Maganti
- & Patrick P. Mercier
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Article
| Open Access
Pre-equilibrium biosensors as an approach towards rapid and continuous molecular measurements
Biosensors using ligand-receptor binding tend to operate under equilibrium conditions, but this can make real-time monitoring challenging. Here the authors provide a theoretical foundation for biosensing where ligand concentrations can be continuously measured without needing to reach equilibrium.
- Nicolò Maganzini
- , Ian Thompson
- & Hyongsok Tom Soh
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Article
| Open Access
A click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples
Accurate detection of antigen p24 for HIV−1 early diagnosis remains challenging. Here the authors present a click chemistry amplified nanopore (CAN) assay that allows p24 quantification at ultralow concentration range in clinical samples.
- Xiaojun Wei
- , Xiaoqin Wang
- & Chang Liu
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Article
| Open Access
A genetically encoded fluorescent biosensor for detecting itaconate with subcellular resolution in living macrophages
Itaconate has been identified as an immunomodulatory metabolite produced by activated macrophages, but methods for detecting itaconate in live cells are lacking. Here, the authors develop a fluorescent biosensor named BioITA for detecting itaconate in subcellular compartments of living macrophages.
- Pengkai Sun
- , Zhenxing Zhang
- & Xinjian Li
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Article
| Open Access
Ultrafast one-minute electronic detection of SARS-CoV-2 infection by 3CLpro enzymatic activity in untreated saliva samples
Methods for the detection of active viral infection are desirable. Here, the authors report an electrochemical approach targeting a SARS-CoV-2 proteolytic enzyme called 3CLpro, as a marker of active infection.
- Ella Borberg
- , Eran Granot
- & Fernando Patolsky
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Article
| Open Access
Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor
β-TrCP plays an important role in diverse cellular processes such as the cell cycle and inflammation. Here the authors develop a biosensor for β-TrCP activity and use it to investigate β-TrCP dynamics during the cell cycle, and to screen a small-molecule library for β-TrCP activators and inhibitors.
- Debasish Paul
- , Stephen C. Kales
- & Steven D. Cappell
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Article
| Open Access
Continuous biomarker monitoring with single molecule resolution by measuring free particle motion
Various applications would benefit from the ability to continuously measure biomolecules. Here the authors describe a biosensing technology based on the free diffusion of biofunctionalized particles hovering over a sensor surface, which enables monitoring of analytes (pM-µM) over long timespans.
- Alissa D. Buskermolen
- , Yu-Ting Lin
- & Menno W. J. Prins
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Article
| Open Access
Ultrathin crystalline-silicon-based strain gauges with deep learning algorithms for silent speech interfaces
Designing an efficient platform that enables verbal communication without vocalization remains a challenge. Here, the authors propose a silent speech interface by utilizing a deep learning algorithm combined with strain sensors attached near the subject’s mouth, able to collect 100 words and classify at a high accuracy rate.
- Taemin Kim
- , Yejee Shin
- & Ki Jun Yu
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Article
| Open Access
Screening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow
Microbial production of cannabinoids promises a cheaper and more sustainable route to these important therapeutic molecules, but strain improvement and screening is challenging. Here, the authors develop a yeast-based Δ9-tetrahydrocannabinol (THC) biosensor for screening microbial mutant libraries.
- William M. Shaw
- , Yunfeng Zhang
- & Tom Ellis
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Article
| Open Access
A nanopore interface for higher bandwidth DNA computing
Toe-hold-mediated strand displacement (DSD) is a widely used molecular tool in applications such as DNA computing and nucleic acid diagnostics. Here the authors characterize dozens of orthogonal barcode sequences that can be used for monitoring the output kinetics of multiplexed DSD reactions in real-time using a commercially-available portable nanopore array device.
- Karen Zhang
- , Yuan-Jyue Chen
- & Jeff Nivala
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Article
| Open Access
Programmable CRISPR-Cas9 microneedle patch for long-term capture and real-time monitoring of universal cell-free DNA
Real-time sensing of biomarkers via the use of wearable devices is a major aim of personalised medicine. Here, authors demonstrate an on-line wearable microneedle patch for real-time capture and monitoring of universal cell-free DNA.
- Bin Yang
- , Jilie Kong
- & Xueen Fang
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Article
| Open Access
Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter
AMP activated protein kinase (AMPK) is a master regulator of cellular metabolism, but how AMPK activity is spatiotemporally regulated remains unclear. Here, Schmitt et al develop a sensitive biosensor for AMPK, which they use to uncover mechanisms for AMPK activity in the lysosome and nucleus.
- Danielle L. Schmitt
- , Stephanie D. Curtis
- & Jin Zhang
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Article
| Open Access
High-resolution mass measurements of single budding yeast reveal linear growth segments
Measuring the mass of individual microbial cells remains challenging. Here, the authors present a cell balance to monitor the proliferation of single budding yeast cells under culture conditions in real time, showing that single cells increase total mass in multiple linear segments of constant growth rates.
- Andreas P. Cuny
- , K. Tanuj Sapra
- & Daniel J. Müller
Ultrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device