All matter has density. The recorded uses of density to characterize matter date back to as early as ca. 250 BC, when Archimedes was believed to have solved “The Puzzle of The King's Crown” using ...density.1 Today, measurements of density are used to separate and characterize a range of materials (including cells and organisms), and their chemical and/or physical changes in time and space. This Review describes a density‐based technique—magnetic levitation (which we call “MagLev” for simplicity)—developed and used to solve problems in the fields of chemistry, materials science, and biochemistry. MagLev has two principal characteristics—simplicity, and applicability to a wide range of materials—that make it useful for a number of applications (for example, characterization of materials, quality control of manufactured plastic parts, self‐assembly of objects in 3D, separation of different types of biological cells, and bioanalyses). Its simplicity and breadth of applications also enable its use in low‐resource settings (for example—in economically developing regions—in evaluating water/food quality, and in diagnosing disease).
A density‐based technique—magnetic levitation (MagLev)—developed and used to solve problems in the fields of chemistry, materials science, and biochemistry is described in this Review. MagLev has two principal characteristics: i) it is density‐based, and thus in principle applicable to all materials, and ii) it is simple—a characteristic that makes it useful for a number of applications.
Due to their portability, versatility for supporting multiple assay formats, and potential for resulting in low-cost assays, paper-based analytical devices (PADs) are an increasingly popular format ...as a platform for the development of point-of-care tests. However, very few PADs have been translated successfully to their intended environments outside of academic settings. Often overlooked as a factor that inhibits translation, usability is a vital characteristic of any successful point-of-care test. Recent advancements in PAD design have demonstrated improved usability by simplifying various aspects of user operation, including sample collection, sample processing, device operation, detection, and readout/interpretation. Field testing at various stages of device design can offer critical feedback about device usability, especially when it involves the proposed end-user or other stakeholders. By highlighting advances in usability, we aim to encourage thoughtful and rigorous design at the academic prototyping stage to address one outstanding hurdle that limits the number of PADs that make it from the benchtop to the point-of-care.
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•Paper-based devices have potential for use at the point-of-care.•Devices that are user-friendly are more likely to be translated to the field.•Additional user steps create additional opportunities for user error.•We discuss ways to streamline user operation of paper-based devices.•We highlight three case studies for devices deployed successfully to the field.
Paper-Based ELISA Cheng, Chao-Min; Martinez, Andres W.; Gong, Jinlong ...
Angewandte Chemie (International ed.),
June 28, 2010, Volume:
49, Issue:
28
Journal Article
Peer reviewed
Paper works: Paper‐based indirect ELISA (see picture) has been demonstrated through the detection of rabbit IgG and the HIV‐1 envelope antigen gp41. This technique combines the sensitivity and ...specificity of ELISA with the low cost and ease‐of‐use of paper‐based platforms.
The quantification of blood cells provides critical information about a patient's health status. Sophisticated analytical equipment, such as hematology analyzers, have been developed to perform these ...measurements, but limited-resource settings often lack the infrastructure required to purchase, operate, and maintain instrumentation. To address these practical challenges, paper-based microfluidic devices have emerged as a platform to develop diagnostic assays specifically for use at the point-of-care. To date, paper-based microfluidic devices have been used broadly in diagnostic assays that apply immunoassay, clinical chemistry, and electrochemistry techniques. The analysis of cells, however, has been largely overlooked. In this communication, we demonstrate a paper-based microfluidic device that enables the controlled transport of red blood cells (RBCs) and the measurement of the hematocrit-the ratio of RBC packed cell volume to total volume of whole blood. The properties of paper, device treatment, and device geometry affect the overall extent and reproducibility of transport of RBCs. Ultimately, we developed an inexpensive (US$0.03 per device) thermometer-styled device where the distance traveled by RBCs is proportional to the hematocrit. These results provide a foundation for the design of paper-based microfluidic devices that enable the separation and detection of cells in limited-resource settings.
Lateral flow tests and hand-held analyzers facilitate diagnostic testing in resource limited settings and at the point-of-care. However, many of these devices require sample preparation such as ...plasma separation to remove cells and isolate the liquid portion of blood. Specifically, the separation of plasma from blood is necessary for routine health assessments such as comprehensive metabolic panels and chronic HIV viral load monitoring. Away from laboratories, this type of processing has been addressed by unconventional, hand-operated centrifuge devices (high volume) or plasma separation membranes (PSM) coupled with lateral flow tests (low volume). Herein, we describe a device that separates and stores plasma from undiluted blood using only passive filtration in less than 10 min. Integrating a PSM with a prefilter and absorbent material yields a 3-fold increase in separation efficiency compared to similar devices using passive filtration. We demonstrate the reproducibility of our device across the physiological range of hematocrits (20–50%) with an average recovered plasma volume of 61.7 ± 2.6 μL. Maximum separation efficiency (53.8%, 65.6 ± 3.9 μL plasma) was achieved for a sample of whole blood (30% hematocrit) in 10 min. We evaluate the purity of our plasma sample by quantitation of hemoglobin and report hemolysis as either minimal (≤5%) or undetectable (≤1%). Specific recovery of human IgG, IFN-γ, and HIV-1 RNA indicate the diagnostic utility of plasma obtained from our device is unchanged compared to plasma obtained via centrifugation. Finally, we demonstrate the use of recovered plasma, applied via “stamping”, to successfully conduct a commercial lateral flow immunochromatographic assay for tetanus antibodies. This device platform is capable of producing pure plasma samples from blood to facilitate tests in resource limited settings to improve access to healthcare.
Abstract
Development of paper-based microfluidic devices that perform colorimetric measurements requires quantitative image analysis. Because the design geometries of paper-based microfluidic devices ...are not standardized, conventional methods for performing batch measurements of regularly spaced areas of signal intensity, such as those for well plates, cannot be used to quantify signal from most of these devices. To streamline the device development process, we have developed an open-source program called ColorScan that can automatically recognize and measure signal-containing zones from images of devices, regardless of output zone geometry or spatial arrangement. This program, which measures color intensity with the same accuracy as standard manual approaches, can rapidly process scanned device images, simultaneously measure identified output zones, and effectively manage measurement results to eliminate requirements for time-consuming and user-dependent image processing procedures.
While a number of assays for soluble analytes have been developed using paper-based microfluidic devices, the detection and analysis of blood cells has remained an outstanding challenge. In this ...Feature, we discuss how the properties of paper determine the performance of paper-based microfluidic devices and permit the design of cellular assays, which can ultimately impact disparities in healthcare that exist in limited-resource settings.
Total and differential white blood cell (WBC) counts are vital metrics used routinely by clinicians to aid in the identification of diseases. However, the equipment necessary to perform WBC counts ...restricts their operation to centralized laboratories, greatly limiting their accessibility. Established solutions for the development of point-of-care assays, namely lateral flow tests and paper-based microfluidic devices, are inherently limited in their ability to support the detection of WBCsthe pore sizes of materials used to fabricate these devices (e.g., membranes or chromatography papers) do not permit passive WBC transport via wicking. Herein, we identify a material capable of the unimpeded transport of WBCs in both lateral and vertical directions: a coffee filter. Through in situ labeling with an enzyme-labeled affinity reagent, our paper-based cytometer detects WBCs according to their immunophenotype. Using two cultured leukocyte lines (Jurkat D1.1 T cells and MAVER-1 B cells), we demonstrate the specific, colorimetric enumeration of each target cell population across the expected physiological range for total lymphocytes, 1000–4000 cells μL–1. Additionally, we highlight a potential application of this type of device as a screening tool for detecting abnormal cell counts outside the normal physiological range and in subclasses of cell types, which could aid in the identification of certain diseases (e.g., CD4+ T lymphocytes, an important biomarker for HIV disease/AIDS). These results pave the way for a new class of paper-based devicesthose capable of controlled white blood cell transport, labeling, capture, and detectionthus expanding the opportunities for low-cost, point-of-care cytometers.
The development of viable point-of-care diagnostic formats is integral to achieving better patient care and improved outcomes. The need for robust and low-cost tests is especially important in ...under-resourced and rural settings. Perhaps the greatest challenge is ensuring that an untrained individual is capable of operating and interpreting the test, out with a care facility. Here we present a paper-based diagnostic device capable of sensing miR-29a using both colorimetric and surface enhanced Raman scattering (SERS) analysis. Rather, than carry out the two types of analyses in tandem, we envisage that the colorimetric output is easy enough to be interpreted by the untrained-individual administering the test to provide them with qualitative feedback. If deemed positive, the test can be further validated at a centralized care facility using a handheld-Raman spectrometer to provide a semi-quantitative result. Detection of miR-29a, a microRNA associated with myocardial infarction, was achieved at a level of pg μL
−1
through the combination of three-dimensional paper-based microfluidics, colorimetric detection, and surface enhanced Raman scattering (SERS) analysis. RGB analysis of the colorimetric output generated from samples containing miR-29a at different concentrations (18-360 pg μL
−1
) showed differentiation from the control sample, however significant repeat variability indicated that it could not be used for quantifying miR-29a levels. However, the SERS analysis exhibited greater reproducibility at varying concentrations, achieving an LoD of 47 pg μL
−1
. The union of the paper-based device and the two analysis methods resulted in the production of a sensitive, reproducible and facile, point of care test (POCT), which paves the way for future implementation in the diagnosis of a range of diseases.
A paper-based microfluidics self-testing device capable of colorimetric and SERS-based sensing of cardiovascular disease associated miR-29a has been developed for improving patient care and triage.
In the wake of the COVID‐19 global pandemic, self‐administered microsampling tools have reemerged as an effective means to maintain routine healthcare assessments without inundating hospitals or ...clinics. Finger‐stick collection of blood is easily performed at home, in the workplace, or at the point‐of‐care, obviating the need for a trained phlebotomist. While the initial collection of blood is facile, the diagnostic or clinical utility of the sample is dependent on how the sample is processed and stored prior to transport to an analytical laboratory. The past decade has seen incredible innovation for the development of new materials and technologies to collect low‐volume samples of blood with excellent precision that operate independently of the hematocrit effect. The final application of that blood (i.e., the test to be performed) ultimately dictates the collection and storage approach as certain materials or chemical reagents can render a sample diagnostically useless. Consequently, there is not a single microsampling tool that is capable of addressing every clinical need at this time. In this review, we highlight technologies designed for patient‐centric microsampling blood at the point‐of‐care and discuss their utility for quantitative sampling as a function of collection material and technique. In addition to surveying methods for collecting and storing whole blood, we emphasize the need for direct separation of the cellular and liquid components of blood to produce cell‐free plasma to expand clinical utility. Integrating advanced functionality while maintaining simple user operation presents a viable means of revolutionizing self‐administered microsampling, establishing new avenues for innovation in materials science, and expanding access to healthcare.
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