Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: In vitro diagnostics and POC solutions.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: In Vitro, Biomarker Discovery, Enzyme-linked Immunosorbent Assay, Diagnostic Assay, Amplification, Virus, CRISPR, Purification, Stripping Membranes

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: Examples of POC Testing (POCT) solutions for biomarker detection and In Vitro Diagnostics (IVDs). a) A POC detection platform for the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein based on a self‐assembled plasmonic nanoprobe array mechanism enabled through Bioinspired Plasmo‐Virus (BPV) particle synthesis, Reproduced with permission. [ ⁴⁰ ] Copyright 2023, American Chemical Society. b) Microfluidic system with integrated tapes for multiplexed detection of inflammatory markers of C‐reactive protein (CRP), Procalcitonin (PCT), and Interleukin‐6 (IL‐6) for early clinical diagnosis of sepsis, Reproduced with permission. [ ⁴² ] Copyright 2022, Elsevier. c) A dry chemistry‐based bipolar Electrochemiluminescence (ECL) immunoassay system for POCT of Alzheimer‐associated neuronal thread protein (AD7c‐NTP), Reproduced with permission. [ ⁴⁷ ] Copyright 2023, American Chemical Society. d) GeneXpert platform, a PCR‐based system for the detection of multiple diseases in various testing settings (Image Reproduced with permission from Cepheid), [ ⁴⁴ ] e) Mass screening of COVID‐19 via detection of breath volatile compounds using a SERS‐based breathalyzer, Reproduced with permission. [ ⁴⁵ ] Copyright 2022, American Chemical Society. f) POC detection of COVID‐19 using electrochemical dual immunosensing of the nucleocapsid protein (N‐protein) via electrochemical impedance spectroscopy (Bi‐ECDAQ), Reproduced with permission. [ ⁵⁸ ] Copyright 2022, Elsevier.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: Biomarker Discovery, In Vitro, Virus, Electrochemiluminescence, Impedance Spectroscopy

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: Microfluidics integrated biosensors. a) Immunobiosensor on a chip for electrochemical detection of COVID‐19 in a self‐powered microfluidic system, Reproduced with permission. [ ⁶³ ] Copyright 2022, Royal Society of Chemistry. b) Multiplexed DNA detection for Malaria diagnosis using an origami‐based paper microfluidic system and lateral flow detection, Reproduced with permission. [ ⁶⁴ ] Copyright 2019, PNAS. c) Paper‐based sample concentration technique in the Lateral Flow Assay (LFA) for detection of Human Immunodeficiency Virus (HIV) nucleic acid, Reproduced with permission. [ ⁶⁵ ] Copyright 2016, Elsevier. d) Programmed passive microfluidic capillary system and embedded Enzyme‐Linked Immunosorbent Assay (ELISA) for detection of SARS‐CoV‐2 antibodies, Reproduced with permission. [ ⁶⁶ ] Copyright 2022, Springer Nature. e) Active microfluidic system for rapid detection of cardiac troponin I (cTnI) through on‐chip ELISA, Reproduced with permission. [ ⁶⁷ ] Copyright 2021, Springer Nature. f) Droplet microfluidic system and integrated Surface‐Enhanced Raman spectroscopy (SERS)‐based sensor, Reproduced with permission. [ ⁶⁸ ] Copyright 2019, Royal Society of Chemistry. g) Autonomous microfluidic system coupled with electrochemical immunosensor for detection of Glial Fibrillary Acidic Proteins (GFAP), Reproduced with permission. [ ⁶⁹ ] Copyright 2022, Royal Society of Chemistry. h) Detection of Staphylococcus aureus DNA via a low‐cost microfluidic integrated isothermal amplification and on‐site nucleic acid quantification; (SIMPLE: Self‐powered Integrated Microfluidic Point‐of‐care Low‐cost Enabling) chip, Reproduced with permission. [ ⁷⁰ ] Copyright 2017, Science.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: Biomarker Discovery, Concentration Assay, Lateral Flow Assay, Virus, Enzyme-linked Immunosorbent Assay, Raman Spectroscopy, Amplification

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: Overview of wearable systems for biomarker detection.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: Biomarker Discovery, Concentration Assay, Fluorescence, Enzyme-linked Immunosorbent Assay, Activity Assay

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: Wearable systems for biomarker detection and on‐site health monitoring. A, a) Colorimetric sweat chloride analysis enabled through skin mount microfluidic system featuring superabsorbent polymer valves, Reproduced with permission. [ ¹¹⁴ ] Copyright 2018, John Wiley and Sons. b) Miniaturized microfluidics and colorimetric analysis for detection of nutrients in sweat and supplying vitamins, Reproduced with permission. [ ⁸⁵ ] Copyright 2021, Wiley‐VCH, c) The Gx sweat patch for personalized sweat rate determination and sweat chloride analysis for athletic use, Reproduced with permission. [ ¹¹⁵ ] Copyright 2023, Springer Nature Limited. d) A sweat patch embedded with electrochemical sensors for C‐reactive protein (CRP) monitoring in sweat, Reproduced with permission. [ ¹⁰³ ] Copyright 2023, Springer Nature Limited, e) MicroSweat: A capillary microfluidic sweat collection patch for stress monitoring via determination of sweat cortisol levels, Reproduced with permissions. [ ⁸⁶ ] Copyright 2022, Wiley‐VCH. f) Electrochemical urine analysis via a wearable diaper sensor for urinary incontinence complications, Reproduced with permission. [ ⁹⁴ ] Copyright 2022, Elsevier. g) Wearable Electroencephalogram (EEG) device with a Brain–AI Closed‐Loop System (BACLoS) for predicting human cognitive consequences, Reproduced with permission. [ ¹¹⁶ ] Copyright 2022, Springer Nature Limited. h) Microfluidics skin interface sweat analysis with a 3D complex structure enabling integration of colorimetric assays evaluating sweat chloride, Reproduced with permission. [ ¹⁰⁵ ] Copyright 2016, The American Association for the Advancement of Science. i) Respiration sensor in wearable format inside a mask for chronic kidney disease monitoring through ammonia (NH 3 ) content measurement, Reproduced with permission. [ ⁹⁵ ] Copyright 2022, American Chemical Society. j) Soft wearable microfluidics for sweat capture, storage, and analysis using the smartphone‐assisted colorimetric technique, Reproduced with permission. [ ¹⁰⁶ ] Copyright 2016, The American Association for the Advancement of Science. B) The procedure of data analysis using AI algorithms from data collection, preprocessing, and dataset split to test and train, training the Machine Learning (ML) or Deep Learning (DL) model, validating the model, and final testing for predictions. C) The output of the wearable systems integrated with AI algorithms can be represented as clustering the data, determining the true or false negative/positive rates, and the accuracy of the model and analysis.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: Biomarker Discovery, Polymer

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: State‐of‐the‐art AI‐enhanced bioassays for disease detection.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: Diagnostic Assay, Avidin-Biotin Assay, Imaging, Marker, Fluorescence, Methylation, Membrane, Sequencing

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: Bioassays and AI. Biological assays including microfluidic assays, in vitro toxicity assays, or immunoassays, as well as protein quantification such as western blotting can be integrated with statistical/ML methods for data analysis, including regression approaches such as Quantitative Structure‐Activity Relationship (QSAR), k‐means clustering, and k‐nearest neighbours, ensemble forest methods, Support Vector Machine (SVM), and Principal Component Analysis (PCA) with applications in enhanced cell tracking, Reproduced with permission. [ ²²⁹ ] Copyright 2023, Frontiers, image processing for paper‐based microfluidics, Reproduced with permission. [ ²³² ] Copyright 2021, American Chemical Society, and protein classification/generation.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: In Vitro, Western Blot, Activity Assay, Plasmid Preparation, Cell Tracking Assay

Journal: Advanced Science

Article Title: Revolutionary Point‐of‐Care Wearable Diagnostics for Early Disease Detection and Biomarker Discovery through Intelligent Technologies

doi: 10.1002/advs.202400595

Figure Lengend Snippet: Integration of microfluidics in the POC systems and platforms for conducting biological assay with AI technologies. A) Various microfluidics elements such as microchannels, valves, and droplet microfluidic systems that can be used for developing platforms to conduct biological assays. Such techniques coupled with sensing modalities enable on‐site biosample analysis with marketed and FDA‐authorized examples including the Maverick™ SARS‐CoV‐2 Multi‐Antigen Serology Panel [ ²⁴⁴ ] (Image reproduced with permission from Genalyte Inc.), or the Minuteful smartphone‐powered kidney test (Image reproduced with permission from Healthy.io Ltd). [ ²⁴⁵ ] The role of AI systems in biological assays and clinical decision‐making is also becoming more established with marketed technologies such as EasyScan One (the newer version of EasyScan Go), a microscopy system for Malaria detection based on machine learning [ ²⁴⁶ ] (Image reproduced with permission from Motic Instruments Inc), and the Tempus one system, one of the latest innovations of the Tempus labs incorporating generative AI solutions in precision medicine (Image reproduced with permission from Tempus). [ ²⁴³ ] Recent research works explore novel applications of the integration of AI systems into the biological assays and biomarker detection systems, including a) AI‐assisted urinary multimarker sensor for prostate cancer screening, Reproduced with permission. [ ²⁰³ ] Copyright 2021, American Chemical Society. b) Electrochemiluminescence biosensor with smart‐phone integrated and machine‐learning assisted algorithm for detection of various metabolites, Reproduced with permission. [ ²⁰⁸ ] Copyright 2023, Elsevier. c) A microfluidic digital immunoassay for inflammatory markers and antibiotics detection empowered by a computer vision‐based AI‐mediated encoding‐decoding system, Reproduced with permission. [ ²⁰⁹ ] Copyright 2023, American Chemical Society. d) Utility of the artificial neural network in processing the light parameters of the fluorescence for optical POC solutions, Reproduced with permission. [ ²¹⁶ ] Copyright 2023, Elsevier. e) High‐throughput SERS‐based classification of the cell secretomes assisted by the machine learning algorithms, Reproduced with permission. [ ²¹⁷ ] Copyright 2023, Wiley VCH.

Article Snippet: Skin‐Interfaced Microfluidic Systems with Spatially Engineered 3D fluidics , Colorimetric , Sweat , – , Health Status , Chloride , Forearm , 8 Healthy Subjects , [ ] .

Techniques: Microscopy, Clinical Proteomics, Biomarker Discovery, Electrochemiluminescence, Fluorescence, High Throughput Screening Assay

Journal: Small (Weinheim an der Bergstrasse, Germany)

Article Title: Fracture-based Fabrication of Normally-closed, Adjustable and Fully Reversible Micro-scale Fluidic Channels

doi: 10.1002/smll.201400147

Figure Lengend Snippet: Crack position on the device surfaces can be predictively controlled by incorporating V-notch microstructures into the h-PDMS/PDMS substrates. Cracks are initiated at these points because the notches shield any intrinsic flaws lying between them [21]. (A) V-notches are fabricated at distinct spacings and an applied strain generates cracks at those locations (scale bar = 200 μm). (B) For V-notches spaced 700 μm apart, cracks can be formed at the notch sites. Applied widening strains up to 25% then provide a stable, normalized spacing without generating additional cracks, enabling the formation of adjustable crack structures at specified locations on the substrate. (C) The cracks at these precisely defined locations have well-controlled widths that depend on the applied strain (linear fit R2 value > 0.97 for all data sets). Hence, the position and width of the reversible cracks can be prescribed accurately.

Article Snippet: Adjustable fluidic structures play an important role in microfluidic systems.

Techniques:

Journal: Small (Weinheim an der Bergstrasse, Germany)

Article Title: Fracture-based Fabrication of Normally-closed, Adjustable and Fully Reversible Micro-scale Fluidic Channels

doi: 10.1002/smll.201400147

Figure Lengend Snippet: Adjustable and reversible microfluidic structures. (A) A schematic cross-section demonstrating the spontaneous formation of a microfluidic crack structure within an h-PDMS layer embedded in a PDMS substrate. (B) Fluorescent dye is flowed through the microfluidic structures to demonstrate fluidic connections and the ability to adjust the size of fracture-based channels. Scale bar: 50 μm. (C) Representative confocal image of the cross-sectional area of a fracture-fabricated microfluidic channel at 20% strain, filled with fluorescent dye. Scale bar: 5 μm. (D) Optical micrograph showing that multiple cracks can be simultaneously generated and reversibly closed to expel liquid from the microfluidic channels. Scale bar: 100 μm. (E) Integrated signal from the red dye is measured over two repeated open-and-close strain cycles, demonstrating that no measurable level of liquid remains within the channel after closure. This finding further establishes that no delamination occurs between the material layers. (F) Diamond-shaped microfabricated cavities in the h-PDMS layer may be used to simultaneously direct crack formation and provide addressable fluid compartments for a variety of applications requiring valved reaction chambers.

Article Snippet: Adjustable fluidic structures play an important role in microfluidic systems.

Techniques: Generated

Journal: Small (Weinheim an der Bergstrasse, Germany)

Article Title: Fracture-based Fabrication of Normally-closed, Adjustable and Fully Reversible Micro-scale Fluidic Channels

doi: 10.1002/smll.201400147

Figure Lengend Snippet: Application of adjustable reversible microstructures to lyse single cells and manipulate released nuclear chromatin. A single HeLa cell with a GFP-labeled H2B histone is trapped in enlarged crack-fabricated microchannels and lysed by compression applied via tension release. Once lysed, the channel is opened and closed, forcing the GFP-labeled chromatin to linearize due to elongational shear forces imposed by the fluid [11], thereby confirming cell lysis. Scale bar = 25 μm.

Article Snippet: Adjustable fluidic structures play an important role in microfluidic systems.

Techniques: Labeling, Shear, Lysis