Paper-Based Diagnostic Devices PDF

73 Advantages of POC diagnosis Easy-to-use/ Self administered: In conventional setting, patients are supervised by a medical team responsible for administering medication and monitoring response. POC tests are widely self-administered, making patients responsible for managing their condi...

73 Advantages of POC diagnosis Easy-to-use/ Self administered: In conventional setting, patients are supervised by a medical team responsible for administering medication and monitoring response. POC tests are widely self-administered, making patients responsible for managing their conditions. Time: POC measurement provides results rapidly. Cost: POC diagnostic cost parameters are different from conventional laboratory analysis. Instruments/devices are smaller and more specialized than laboratory systems, hence cost less. 74 Paper based diagnosis Sensitive and specific User-friendly Rapid and robust Equipment free, they are mainly read with the naked eye, or, if a quantitative detection is required, the equipment is small and cheap. Deliverable to end-users Can be developed using inkjet, wax printing or screen-printing technology, making them amenable to in-situ fabrication. 75 Types of paper-based diagnostics Microfluidic paper Lateral flow assays Dipstick assays analytical devices (LFAs) (µPADs) 76 Dipstick assays Dipstick assays are the simplest ones, since they are based on the blotting of the sample on to a paper pre-stored with reagents. Dipsticks are sample to design, easy to manufacture and convenient to use. pH test strips are manufactured by soaking a piece of filter paper into a mixture of acid-alkali indicators with certain concentration ratio. Once dried, the paper is impregnated with detection reagents. When an unknown sample is dispensed on the paper, the detecting reagents react with the analyte (H+) and develop a colour. By referring to a standard indicator card, the pH value of the solution can be indicated and thus the concentration of H+ is semi-quantified. Urine test strips have been designed to detect metabolic products in urine (e.g.protein, glucose, and salt), which have become basic diagnostic tools to indicate pathological changes. 77 Lateral Flow Assays (LFAs) LFAs have all the reagents pre-stored in the strip, as the dipstick, but they also integrate the flow of the sample. The flow passes through the different zones of the strip, which have different reagents for different functions. LFA is generally made of 4 different parts: the sample pad, the conjugation pad, the detection pad and the absorbent pad. There are two formats, i.e., sandwich and competitive (or inhibition) formats, for LFAs. In general, sandwich format assays are utilized for an analyte with multiple antigen epitopes, while competitive format assays are designed to detect an analyte with a single antigen epitope. 78 Components Of A Lateral Flow Rapid Test Strip: Sample pad: an adsorbent pad onto which the test sample is applied. Conjugate or reagent pad: containing antibodies specific to the target analyte conjugated to coloured particles. Reaction membrane: usually a nitrocellulose or cellulose acetate membrane onto which anti- target analyte antibodies are immobilized in a line that crosses the membrane to act as a capture zone or test line (a control zone present containing antibodies specific for conjugate antibodies) Wicking pad or waste reservoir: another adsorbent pad designed to draw the sample across the reaction membrane by capillary action and collect it. 79 LFAs display of results 80 Microfluidic paper analytical device (μPADs ) μPADs are made by patterning paper with a variety of assay designs, mainly based on capillary force to drive aqueous fluid movement. Two-dimensional (2D) and three-dimensional (3D) μPADs have been developed. 2D μPADs are made by patterning physical or chemical hydrophobic boundaries to form micro channels on paper. Various approaches, including cutting, photolithography, plotting, inkjet etching, plasma etching, wax printing, etc., have been used to create channels and barriers in paper. 2D μPADs The dimensions of the resulting channels together with the characteristics of paper and ambient conditions (temperature and humidity) can affect the wicking rate of fluid. The reagents required for biochemical reactions can be immobilized on paper with different patterns (e.g.,four-leaf clover) by hand dispensing or ink jet printing. 81 Microfluidic paper analytical device (μPADs ) Functional chemical or biological molecules can be immobilized on paper by physical absorption, chemical coupling, and carrier-mediated deposition. When the reagents are dried, the paper-based devices can be used for biochemical analyses. 3D μPADs are produced by stacking layers of patterned paper in such a way that channels in adjacent layers of paper connect with each other. Compared with 2D μPADs, 3D μPADs have several advantages due to their capability to incorporate complex networks of channels, thus providing multiple functionalities. 3D μPADs 82 Mechanism of action in paper-based diagnosis The reaction mechanisms in paper-based diagnosis can be categorized into the following: Chemical reaction based Biological reaction Electrochemical reaction 83 Chemical: Colour Change Most chemical reactions with colour change can be achieved on paper, such as acid–alkali reaction, precipitation reaction, redox reaction and enzymatic reaction. Involve a one-step procedure. pH test strips can be dispensed with several compounds to exhibit different color changes in response to different pH values. Semi-quantitative detection of H+ concentrations of solutions can then be achieved by grading the pH values of solutions from 1 to14. 84 Biological: Antigen-Antibody binding Antigen–antibody binding based immunoassays detect either antigen or antibody present in a clinical sample. Home pregnancy test strips have been one of the most successful diagnostic paper–based immunoassays so far. It measures a hormone, human chorionic gonadotropin (hCG), in urine from pregnant women. hCG is a hetero dimeric glycoprotein with α and β subunits. Home pregnancy test strips just make use of β subunit (unique to hCG) and contain three kinds of antibodies, i.e., anti-hCG antibody, monoclonal antibody (MAb) and immunoglobin G (IgG). This idea has been used to measure tumor markers, e.g., primary hepatic carcinoma and to diagnose infectious diseases, e.g., AIDS. 85 Electrochemical reaction Electrochemical detection can be achieved on the basis of both redox reactions and non-redox reactions. Redox reactions are involved in electrons transfer between molecules or particles (e.g.,enzyme and nanoparticles), while non-redox reactions are related with the changes of electrical properties, such as impedance, resistance, conductance, and potential. The most successful example of electrochemical detection is the blood glucose meter and test strip for diabetic patients. The glucose meter is an amperometer, and it measures the quantity of electroactive species as a result of the oxidation of glucose by reagents stored in the test strips. Test strip is impregnated with glucose oxidase and other components (e.g. ferrocyanide). When a drop of blood is added, glucose oxidase catalyses the oxidation of glucose, and the glucose meter quantifies the electrons generated by the oxidation and correlates them to the level of glucose in blood. 86 Nanotechnology in point-of-care testing 87 Nanotechnology in Glucose detection: Photonic Nanosensor A boronic acid functionalized hydrogel was formed and included suspended silver nanoparticles. The functionalized hydrogel swelled and contracted in proportion to glucose concentration, as a result of the binding interaction between glucose and the boronic acid. As the hydrogel swells, the distance between the Au NPs modulates in response to glucose concentration, and thereby causes a shift in the wavelength of the refracted light. A wavelength shift of 350 nm across the visible spectrum was reported for glucose concentrations ranging from 0 mM to 10 mM. Yetisen et al. Nano Lett 2014, 14,3587–3593 88 Non-invasive Devices Nano-engineered silica glass with ions that fluoresce in infrared light when a low power laser light hits them. When the glass is in contact with the users’ skin, the extent of fluorescence signal varies in relation to the concentration of glucose in their blood. The device measures the length of time the fluorescence lasts for and uses that to calculate the glucose level in a person’s blood stream without the need for a needle. This process takes less than 30 seconds. 89 Continuous Glucose Monitoring (CGM) Systems Tiny sensor inserted under the skin. Sends information about glucose levels via radio waves from the sensor to a pager like wireless monitor. Helps the patient or the physician to adjust insulin according to requirements. Leads to better glycemic level. Lee et al. Biosensors and Bioelectronics 181 (2021) 113054 90 Smart Nano-Tattoos Tattoo-based platform for noninvasive glucose sensing. (A) Schematic of the printable iontophoretic-sensing system displaying the tattoo-based paper (purple), Ag/AgCl electrodes (silver), Prussian Blue electrodes (black), transparent insulating layer (green), and hydrogel layer (blue). (B) Photograph of a glucose iontophoreticsensing tattoo device applied to a human subject. (C) Schematic of the time frame of a typical on-body study and the different processes involved in each phase. Bandodkar et al. Anal. Chem. 2015, 87, 394−398 91 Nanotechnology in early cancer detection assays Cancer biomarkers detection with NP-assisted ICP-MS signal amplification Cell surface sialic acid assay for estimating the expression level of sialic acids on the cancer cell surface by detecting AuNP signal enhancement in ICP-MS. Zhang et al. Analyst, 141 (2016), pp. 1286-1293 92 Nanotechnology For In Vitro And In Vivo Bioimaging Of Oral Cancer 93 Quantum Dots in cancer detection Zhu et al. Small. 2017;13:1602309. 94 Paper-based analytical device Paper-based analytical device (PAD) for the detection of carcinoembryonic antigen (CEA) via fluorescence energy transfer (FRET). Xu et al. Sci. Rep., 6 (2016), p. 23406 95 NPs based electrochemi-luminescent (ECL) detection of prostate-specific antigen (PSA) The fabrication of an immunosensor, where the Ag@Pb(II)-β-CD (AgNPs on a metal-organic framework (MOF) of β- cyclodextrin and lead ions) was dropped on to the surface of a well-polished glass carbon electrode (GCE) as the working electrode. After surface modification with anti-PSA and bovine serum albumin (BSA), the electrode was inserted into the ECL cell for PSA detection Ma et al. Biosens. Bioelectron., 79 (2016), pp. 379-385 96 SERS based sensors for cancer detection Surface-enhanced Raman scattering (SERS) sensor based on AuNPs formed in situ on a reduced graphene oxide (RGO) film for the detection of volatile organic compound (VOC) biomarkers in human breath. Processed Raman spectra of VOC biomarker patterns was compared with the of samples from healthy individuals, early gastric cancer patients and advanced gastric cancer patients. Chen et al. ACS Nano, 10 (2016), pp. 8169-8179 97 Nanoparticles in MRI 98 Gd-Carbon nanomaterials as MRI contrast agents The tubes were made by treating single-walled carbon nanotubes, SWNTs, which are normally quite long, >1000nm, withfluorine, followed by pyrolysis at a 1000 C. This treatment cut the SWNTs into smaller, ultra-short, nanotubes (20–100nm long) and caused them to be pitted; that A single US-tube loaded with hydrated Gd3+ is, missing carbon atoms on their surface. ions. Gd3+ ion loading is likely through side- Low concentrations of Gd3+@US-tubes could be used to wall defects created by cutting full length bring about the same level of MRI enhancement as produced nanotubes to produce bundled US-tubes. These Gd3+n@US-tube species are linear by other agents, which, since lower concentration of the CA superparamagnetic molecular magnets with would need to be administered, would be beneficial to the Magnetic Resonance Imaging (MRI) efficacies patient. 40 to 90 times larger than any Gd3+-based contrast agent (CA) in current clinical use. Sitharaman et al. Chem Commun. 2005; 915-917 99 Advantages of Gd-Carbon based nanomaterials MRI contrast agents 1. Reduced amount of the contrast agent required to obtain reliable images. 2. Easy targeting of the contrast agent towards specific cells, tissues or molecules 3. Potential for the design of multifunctional nanoprobes 4. Cell labelling capability MRI of Gd@C82 (OH)40 and the Gd-DTPA phantom illustrate that with an equivalent concentration of gadolinium and the gadofullerenes, the latter had the strongest signal Mikawa et al. Bioconjugate Chem. 2001; 12: 510-514 100 Functionalized gadofullerenes developed for the detection of breast cancer (A) the functionalized gadofullerenes ZD2- Gd3N@C80 and their tumour targeting capability. The MCF-7 and MDA-MB- 231 cells lines were used to obtain low- risk and high-risk breast cancer xenografts, respectively. (B) The functionalized gadofullerenes afforded a specific MRI detection of high-risk breast cancer xenografts. Tumour locations are indicated with white arrow heads. Han et al. Nat Commun. 2017; 8: 692 101 Magnetic Nanoparticles for MRI contrast enhancement Fe3+@polyDOPA-b- polysarcosine, a T1-Weighted MRI Contrast Agent. Offering clinical application of Fe3+-based polypept(o)ides in diagnostic radiology as Gd-free MRI contrast agents. Miao et al. ACS Macro Lett. 2018, 7, 6, 693–698 102 Synthesis And Surface Modification Of Magnetic Nanoparticles 103 Nanoparticles in CT 104 Nanoparticles in Computed Tomography (CT) Computed tomography, CT, or sometimes CAT, is a fast and relatively inexpensive way to diagnose disease. The approach involves the passage of x-rays through the patient, where in the x-ray source and detector are moved relative to a target area in the body. If the iodinated compound localizes in the fluid surrounding diseased tissue, the contrast between diseased and normal tissue will be enhanced, thereby allowing the physician to arrive at firmer conclusions concerning the state and progression of the disease. To increase the scattering between diseased and normal tissue, patients are often given iodinated organic compounds. 105 106 Gold nanoparticles as CT contrast agents Gold nanoparticles (AuNPs), with high X- ray attenuation and K-edge energy (80.7 keV), can provide higher imaging contrast at high X-ray tube voltages than iodinated CT contrast agents at the same concentration 8. AuNPs also allow facile surface modifications to increase their TEM images of (A) gold nanospheres, (B) gold nanorods, (C) biocompatibility and durability due to gold nanostars, (D) gold nanoplates, (E) gold nanocages, (F) gold nanoshells, (G) Au2Pt NPs, (H) Gd-Au NPrs their high affinity for thiol derivatives Jiang et al. Theranostics. 2023; 13(2): 483–509 107 Bismuth nanoparticles as CT contrast agents Bismuth (Bi) possesses a higher atomic number (Bi: 83, Au: 79) and larger X-ray attenuation coefficient (Bi: 5.74 cm2/g, Au: 5.16 cm2/g, at 100 keV) than Au, and is a promising CT contrast agent for diagnosis of diseases. As a noble metal, the high cost of Au inevitably limits its applications in clinical practice. However, Bi is a relatively cheap and low-toxic heavy metal and has been used as a pharmaceutical ingredient to treat various diseases, such as gastritis, dyspepsia, ulcers, and infections. Bismuth-based NPs. (A) BiNPs, (B) Bi2S3 NPs, (C) Bi2S3 Bi nanoparticles (BiNPs) can improve the X-ray nanorods, (D) Bi2Se3 nanodots, (E) (BiO)2CO3 nanotubes, (F) absorption efficiency and address the bottleneck of (BiO)2CO3 nanoclusters, (G) HA-Bi2O3 NPs, (H) Cu3BiS3 NDs, (I) BiOI@Bi2S3 NPs. CT imaging contrast agents in terms of sensitivity Jiang et al. Theranostics. 2023; 13(2): 483–509 108