Biomedicine is one of the fastest growing areas of additive manufacturing.Especially,in the field of in vitro diagnostics(IVD),contributions of 3D printing include i)rapid prototyping and iterative IVD proof-of-concep...Biomedicine is one of the fastest growing areas of additive manufacturing.Especially,in the field of in vitro diagnostics(IVD),contributions of 3D printing include i)rapid prototyping and iterative IVD proof-of-concept designing ranging from materials,devices to system integration;ii)conceptual design simpli-fication and improved practicality of IVD products;iii)shifting the IVD applications from centralized labs to point-of-care testing(POCT).In this review,the latest developments of 3D printing and its advantages in IVD applications are summarized.A series of 3D-printed objects for IVD applications,including single-function modules,multi-function devices which integrate several single-function modules for specific an-alytical applications such as sample pre-treatment and chemo-/bio-sensing,and all-in-one systems which integrate multi-function devices and the instrument operating them,are analyzed from the perspective of functional integration.The current and potential commercial applications of 3D-printed objects in the IVD field are highlighted.The features of 3D printing,especially rapid prototyping and low start-up,en-able the easy fabrication of bespoke modules,devices and systems for a range of analytical applications,and broadens the commercial IVD prospects.展开更多
Sweat-based diagnostics offer an exciting avenue to noninvasively monitor analytes which had previously only been avail-able through painful blood draws.Sweat is enriched with physiologically valuable information,and ...Sweat-based diagnostics offer an exciting avenue to noninvasively monitor analytes which had previously only been avail-able through painful blood draws.Sweat is enriched with physiologically valuable information,and recent proteomic studies have identified numerous critical analytes which have highly correlated levels in blood,interstitial fluid and sweat.How-ever,usage of sweat for health monitoring has not been studied extensively due to the substantial challenge of assembling a composite clinic-ready device.Recent advances in soft electronics have made this goal realizable,as these devices can perform electronic or optical monitoring on a flexible substrate using small volumes of liquid.While this field is still in its infancy,this review examines the physiological composition of sweat,various improvements in material science that improve sensor design,existing FDA approvals,methods of extracting sweat and comparisons to blood-based tests.Furthermore,this review assesses the critical challenges which must be overcome for this type of technology to make it out of research laboratories and into continuous clinical use.We believe that once properly harnessed,sweat-based diagnostics can provide patients a painless monitoring tool which can be customized to track a wide variety of medical conditions from the comfort of a patient’s own home.展开更多
Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic...Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip.In this review,we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years.Particularly,we summarize current materials used for microfluidic chip fabrication,discuss the innovation of versatile integrated microfluidic devices,especially the strategies for simplifying sample preparation in manual or self-driven systems,and new detection methods of microfluidic chips.In addition,we describe new integrated microfluidic devices for POC diagnostics of protein-targeted immunodiagnostics,nucleic acid molecular tests,and small molecule metabolites analysis.We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.展开更多
Rapid and sensitive detection of targeted biomarkers in trace samples is of great significance for early in vitro diagnosis of diseases.Microfluidic technology has competitive advantages in this field due to its low c...Rapid and sensitive detection of targeted biomarkers in trace samples is of great significance for early in vitro diagnosis of diseases.Microfluidic technology has competitive advantages in this field due to its low cost,high efficiency,and high portability;however,the analysis of results tends to rely on bulky and sophisticated instruments,and this limits its applications.In this work,we developed a Raspberry Pi camera-based biomarker detection device based on microfluidic technology and digital image colorimetry.For highly sensitive biomarker detection on microfluidic chips,we propose a three-step signal-amplification colorimetric detection strategy consisting of:(1)the release of Ag^(+)ions from silver nanoparticles,(2)Ag^(+)-inhibited urea hydrolysis colorimetry,and(3)microscopic lens magnification.For efficient evaluation of results,we employed an RGB image-processing system to quantitatively analyze color images captured by the Raspberry Pi camera.Further,we tested the functionality of the device with procalcitonin(PCT)in phosphate-buffered saline,plasma,and serum to simulate clinical situations.We determined the limit of detection as 1 ng/ml,and a good linear relationship was established between PCT concentration and color intensity within the detection range 1–10 ng/ml.Importantly,only a relatively short detection time(40 min)was required in all three environments.The results demonstrate the great potential of this device for biomarker detection and facilitating biomedical research.展开更多
Cas12f possesses both cis-and trans-cleavage activities,with the former being extensively studied for its application in genome editing,while the latter remains less explored,particularly for diagnostic purposes,and i...Cas12f possesses both cis-and trans-cleavage activities,with the former being extensively studied for its application in genome editing,while the latter remains less explored,particularly for diagnostic purposes,and is mostly focused on Un1Cas12f1.In this study,we conducted a comprehensive comparison of the trans-cleavage activities of four characterized Cas12f proteins,demonstrating that all four exhibit trans-DNase activity triggered by double-stranded DNA(dsDNA),single-stranded DNA(ssDNA),and single-stranded RNA(ssRNA).Additionally,we identified distinct base preferences for trans-cleavage substrates among these proteins.Our further investigation into the activities of Cas12f revealed the intricate relationship between cis-and trans-cleavage activities under various conditions.Our study provides a multifaceted characterization of the trans-cleavage features of Cas12f nucleases,offering new avenues for a deeper comprehension of the mechanisms underlying Cas12f's functionality.展开更多
基金supported by the National Nat-ural Science Foundation of China(No.51975597)the Guang-dong Natural Science Foundation(No.2020A1515010661)+2 种基金the Sci-ence and Technology Project of Guangzhou(No.201803020026)the General Program of Shenzhen Innovation Funding(Nos.JCYJ20170818164246179 and JCYJ20170307140752183)the Fundamental Research Funds for the Central Universities(No.20lgzd27).
文摘Biomedicine is one of the fastest growing areas of additive manufacturing.Especially,in the field of in vitro diagnostics(IVD),contributions of 3D printing include i)rapid prototyping and iterative IVD proof-of-concept designing ranging from materials,devices to system integration;ii)conceptual design simpli-fication and improved practicality of IVD products;iii)shifting the IVD applications from centralized labs to point-of-care testing(POCT).In this review,the latest developments of 3D printing and its advantages in IVD applications are summarized.A series of 3D-printed objects for IVD applications,including single-function modules,multi-function devices which integrate several single-function modules for specific an-alytical applications such as sample pre-treatment and chemo-/bio-sensing,and all-in-one systems which integrate multi-function devices and the instrument operating them,are analyzed from the perspective of functional integration.The current and potential commercial applications of 3D-printed objects in the IVD field are highlighted.The features of 3D printing,especially rapid prototyping and low start-up,en-able the easy fabrication of bespoke modules,devices and systems for a range of analytical applications,and broadens the commercial IVD prospects.
基金the National Science Foundation under NSF Cooperative Agreement(Nos.EEC-1648451 and EEC-1647837)Dr.Li also thanks the support sponsored by NSF Independent Research/Development(IRD)Program.
文摘Sweat-based diagnostics offer an exciting avenue to noninvasively monitor analytes which had previously only been avail-able through painful blood draws.Sweat is enriched with physiologically valuable information,and recent proteomic studies have identified numerous critical analytes which have highly correlated levels in blood,interstitial fluid and sweat.How-ever,usage of sweat for health monitoring has not been studied extensively due to the substantial challenge of assembling a composite clinic-ready device.Recent advances in soft electronics have made this goal realizable,as these devices can perform electronic or optical monitoring on a flexible substrate using small volumes of liquid.While this field is still in its infancy,this review examines the physiological composition of sweat,various improvements in material science that improve sensor design,existing FDA approvals,methods of extracting sweat and comparisons to blood-based tests.Furthermore,this review assesses the critical challenges which must be overcome for this type of technology to make it out of research laboratories and into continuous clinical use.We believe that once properly harnessed,sweat-based diagnostics can provide patients a painless monitoring tool which can be customized to track a wide variety of medical conditions from the comfort of a patient’s own home.
基金Fundamental Research Funds for the Central Universities,Grant/Award Number:ZQN-818State Key Laboratory of Chemo/Biosensing and Chemometrics,Grant/Award Number:2019006+1 种基金Natural Science Foundation of Fujian Province,China,Grant/Award Number:2021J01310National Natural Science Foundation of China,Grant/Award Numbers:21775128,21804022。
文摘Given the continuous and growing demand for point of care(POC)diagnostic tests,attention has been shifted toward integration and miniaturization of laboratory protocols into“sample-in-answer-out”devices.Microfluidic technologies have been considered an ideal solution to address the requirements of POC diagnostics since many laboratory functions can be miniaturized and incorporated onto a single integrated chip.In this review,we summarize the advances of integrated microfluidic devices for POC diagnostics in the last 3 years.Particularly,we summarize current materials used for microfluidic chip fabrication,discuss the innovation of versatile integrated microfluidic devices,especially the strategies for simplifying sample preparation in manual or self-driven systems,and new detection methods of microfluidic chips.In addition,we describe new integrated microfluidic devices for POC diagnostics of protein-targeted immunodiagnostics,nucleic acid molecular tests,and small molecule metabolites analysis.We also provide future perspectives and current challenges for clinical translation and commercialization of these microfluidic technologies.
基金supported by the National Key Research and Development Program of China(Grant Nos.2023YFA0915200 and 2023YFA0915204)Outstanding Young Scientist in Shandong Province(Grant No.ZR2024YQ064)+4 种基金Shandong Province Science and Technology Small and Medium Enterprises Innovation Capacity Improvement Project(Grant No.2024TSGC008)Shandong Provincial Key Research and Development Project(Grant Nos.2020CXGC011304 and 2022CXGC020206)Taishan Scholar Foundation of Shandong Province(Grant No.tsqn202408256)the Major Innovation Project for the Science Education Industry Integration Pilot Project of Qilu University of Technology(Shandong Academy of Sciences)(Grant No.2023JBZ03)Shanghai Science and Technology Development Funds(Grant No.23J21900100).
文摘Rapid and sensitive detection of targeted biomarkers in trace samples is of great significance for early in vitro diagnosis of diseases.Microfluidic technology has competitive advantages in this field due to its low cost,high efficiency,and high portability;however,the analysis of results tends to rely on bulky and sophisticated instruments,and this limits its applications.In this work,we developed a Raspberry Pi camera-based biomarker detection device based on microfluidic technology and digital image colorimetry.For highly sensitive biomarker detection on microfluidic chips,we propose a three-step signal-amplification colorimetric detection strategy consisting of:(1)the release of Ag^(+)ions from silver nanoparticles,(2)Ag^(+)-inhibited urea hydrolysis colorimetry,and(3)microscopic lens magnification.For efficient evaluation of results,we employed an RGB image-processing system to quantitatively analyze color images captured by the Raspberry Pi camera.Further,we tested the functionality of the device with procalcitonin(PCT)in phosphate-buffered saline,plasma,and serum to simulate clinical situations.We determined the limit of detection as 1 ng/ml,and a good linear relationship was established between PCT concentration and color intensity within the detection range 1–10 ng/ml.Importantly,only a relatively short detection time(40 min)was required in all three environments.The results demonstrate the great potential of this device for biomarker detection and facilitating biomedical research.
基金supported by HPC Platform of Shanghai Tech UniversityThis work was financially supported by grants 2023YFC3403400 and 2022YFC3400200+3 种基金from National KeyR&D Program of China,22277078 and 22207074from the National NaturalScience FoundationofChina,23HC1400800,22ZR1480100,and 22YF1428100the Shanghai Committee of Science and Technology,China,and KF-202303National Center for Protein Sciences at Peking University.
文摘Cas12f possesses both cis-and trans-cleavage activities,with the former being extensively studied for its application in genome editing,while the latter remains less explored,particularly for diagnostic purposes,and is mostly focused on Un1Cas12f1.In this study,we conducted a comprehensive comparison of the trans-cleavage activities of four characterized Cas12f proteins,demonstrating that all four exhibit trans-DNase activity triggered by double-stranded DNA(dsDNA),single-stranded DNA(ssDNA),and single-stranded RNA(ssRNA).Additionally,we identified distinct base preferences for trans-cleavage substrates among these proteins.Our further investigation into the activities of Cas12f revealed the intricate relationship between cis-and trans-cleavage activities under various conditions.Our study provides a multifaceted characterization of the trans-cleavage features of Cas12f nucleases,offering new avenues for a deeper comprehension of the mechanisms underlying Cas12f's functionality.
