Rapid and affordable detection of analytes is critical in diagnostic technologies, but current methods are typically expensive and unsuitable for field detection. Lipidic cubic phases are optically isotropic, transparent lyotropic liquid crystals (LC), containing highly confined water nanochannels in‐between percolating lipid bilayers following defined space groups. Due to this nanoconfinement, the water in these systems provides a unique environment for chemical and enzymatic reactions. Here, it is shown that during the in meso peroxidase enzymatic reaction, the converted product crystallizes within the mesophase domains, generating a detectable birefringence signal and a new general assay principle is presented for the detection of an unprecedented vast class of analytes using such birefringence as sole optical output signal. By exploiting bienzymatic cascade reactions or introducing an enzyme‐linked immunosorbent assay based on birefringence (Birefringent‐ELISA), this approach is used for real‐time detection of exemplary analytes, such as glucose and cholesterol, model pathogenic microorganisms, Escherichia coli, and viruses such as Ebola and HIV. It is also shown how the same technology enables the rapid, naked‐eye screening of malaria infection via in meso detection of hemozoin crystallites. This new technology is general and readily adaptable to the rapid detection of virtually any type of analyte, such as disease biomarkers, viruses, bacteria, and parasites.

Background: Conventional home blood glucose measurements require a sample of blood that is obtained by puncturing the skin at the fingertip. To avoid the pain associated with this procedure, there is high demand for medical products that allow glucose monitoring without blood sampling. In this review article, all such products are presented. Methods: In order to identify such products, four different sources were used: (1) PubMed, (2) Google Patents, (3) Diabetes Technology Meeting Startup Showcase participants, and (4) experts in the field of glucose monitoring. The information obtained were filtered by using two inclusion criteria: (1) regulatory clearance, and/or (2) significant coverage in Google News starting in the year 2016, unless the article indicated that the product had been discontinued. The identified bloodless monitoring products were classified into three categories: (1) noninvasive optical, (2) noninvasive fluid sampling, and (3) minimally invasive devices. Results: In total, 28 noninvasive optical, 6 noninvasive fluid sampling, and 31 minimally invasive glucose monitoring products were identified. Subsequently, these products were characterized according to their regulatory, technological, and consumer features. Products with regulatory clearance are described in greater detail according to their advantages and disadvantages, and with design images. Conclusions: Based on favorable technological features, consumer features, and other advantages, several bloodless products are commercially available and promise to enhance diabetes management. Paths for future products are discussed with an emphasis on understanding existing barriers related to both technical and non-technical issues.

Abstract Background Hepatitis C virus (HCV) screening is critical to HCV elimination efforts. Simplified diagnostics are required for low-resource settings and difficult-to-reach populations. This retrospective study assessed performance of rapid diagnostic tests (RDTs) for detection of HCV antibodies. Methods Two lots of 13 RDTs were evaluated at three laboratories using archived plasma samples from four countries (Nigeria, Georgia, Cambodia, Belgium). HCV status was determined using three reference tests according to a composite algorithm. Sensitivity and specificity were evaluated in HIV infected and HIV uninfected populations. Operational characteristics were also assessed. Results In total, 1,710 samples met inclusion criteria. In HIV uninfected samples (n=384), the majority of RDTs had sensitivity ≥98% in one or both lots and most RDTs had specificity ≥99%. In HIV infected samples (n=264), specificity remained high, but sensitivity was markedly lower than in HIV uninfected samples; only one RDT reached >95%. The majority of HIV infected samples for which sensitivity was low did not have detectable HCV viral load/core antigen. Inter-reader variability, lot-to-lot variability and rate of invalid runs were low for all RDTs (<2%). Conclusion HCV RDTs should be evaluated in the intended target population, as sensitivity can be impacted by population factors such as HIV status.

BackgroundDetection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens.MethodsWe generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection.ResultsOur VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection.ConclusionsThe HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes.

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The development and implementation of a multicancer early detection (MCED) test that is effective and affordable has the potential to change cancer care systems around the world. However, careful consideration is needed within the context of different health care settings (both low-and middle-income countries and high-income countries) to roll out an MCED test and promote equity in access. Cancer 2022;128:875-882.

A key component of any health system is the capacity to accurately diagnose individuals. One of the six building blocks of a health system as defined by the World Health Organization (WHO) includes diagnostic tools. The WHO’s Noncommunicable Disease Global Action Plan includes addressing the lack of diagnostics for noncommunicable diseases, through multi-stakeholder collaborations to develop new technologies that are affordable, safe, effective and quality controlled, and improving laboratory and diagnostic capacity and human resources. Many challenges exist beyond price and availability for the current tools included in the Package of Essential Noncommunicable Disease Interventions (PEN) for cardiovascular disease, diabetes and chronic respiratory diseases. These include temperature stability, adaptability to various settings (e.g. at high altitude), need for training in order to perform and interpret the test, the need for maintenance and calibration, and for Blood Glucose Meters non-compatible meters and test strips. To date the issues surrounding access to diagnostic and monitoring tools for noncommunicable diseases have not been addressed in much detail. The aim of this Commentary is to present the current landscape and challenges with regards to guidance from the WHO on diagnostic tools using the WHO REASSURED criteria, which define a set of key characteristics for diagnostic tests and tools. These criteria have been used for communicable diseases, but so far have not been used for noncommunicable diseases. Diagnostic tools have played an important role in addressing many communicable diseases, such as HIV, TB and neglected tropical diseases. Clearly more attention with regards to diagnostics for noncommunicable diseases as a key component of the health system is needed.

BackgroundThe detection of HIV-1 p24 antigen in diagnostic tests relies on antibodies binding to conserved areas of the protein to cover the full range of HIV-1 subtypes. Using a panel of 43 different virus-like particles (VLPs) expressing Gag from clinical HIV-1 isolates, we previously found that some highly sensitive tests completely failed to detect p24 of certain VLPs, seemingly unrelated to their subtype. Here we aimed to investigate the reason for this failure, hypothesising that it might be due to single amino acid variations in conserved epitopes.MethodsUsing amino acid alignment, we identified single amino acid variations at position 16 or 170 of p24, unique to those VLPs that failed to be detected in certain diagnostic tests. Through DNA-mutagenesis, these amino acids were changed to ones more commonly found at these positions. The impact of these changes on p24 detection was tested in commercial diagnostic tests as well as by Western Blot and ELISA, using epitope-specific antibodies.Results and ConclusionsChanging positions 16 or 170 to consensus amino acids restored the detection of p24 by the investigated diagnostic tests as well as by epitope-specific antibodies in Western Blot and ELISA. Hence, single amino acid changes in conserved epitopes can lead to the failure of p24 detection and thus to false-negative results. To optimise HIV diagnostic tests, they should also be evaluated using isolates which harbour less-frequent epitope variants.