Excited state absorption is the absorption of light by electrons already in an excited state. This requires two photons and equal separation between the ground state, first excited state, and second excited state of a single ion. Energy transfer up-conversion requires two ions, a sensitizer and an activator. In this process, the sensitizer ion is excited and sequentially transfers its energy to the ground state and first excited state of the activator ion. Other up-conversion mechanisms include photon avalanche and cross relaxation. UCPs have been utilized as labels for both protein and nucleic acid targets in lateral flow assays for a variety of infectious diseases.
Recently, Corstjens et al. CAA is present in the serum and urine of patients with Schistosoma infections of all known species and has been found to correspond well with worm burden, clearing soon after successful treatment. The CAA lateral flow assay format is similar to conventional lateral flow assays. CAA-specific antibodies are printed on the test line, and antimouse IgG is printed on the control line.
The workflow of the assay in its current form, however, differs from a typical field-ready test. First, a trichloroacetic acid TCA extraction is performed on a urine or serum sample, requiring a centrifugation step. The test is allowed to develop and must dry completely at least 3 h before scanning and analyzing the strip.
To increase the analytical sensitivity of the assay, Corstjens et al. This allowed for CAA in urine sample volumes of 0. The resulting detection limits improved as sample volume increased, reaching as low as 0. To demonstrate clinical applicability, the concentration step was successfully performed on 2 mL patient urine samples from Kenya high-endemic, S. Further, the additional concentration step increased the cost of this ultrasensitive CAA assay, though sample pooling could make this test more cost-effective and allow for monitoring of worm burdens at the subpopulation level for large-scale surveillance.
In this format, the UCP crystals are the same for each biomarker, though they are functionalized with target-specific antibodies. One disadvantage of highly multiplexed assays on a single strip is the potential increase in cross-reactivity and nonspecific binding that could lead to false-positive results. To mitigate this risk, Hong et al. One unexplored application of multiplexed detection on a lateral flow assay is the use of UCP particles with identical excitation but differing emission profiles.
This could be particularly advantageous for large biomarkers with multiple accessible epitopes and could provide additional clinical information. For example, an assay that captures and detects whole organisms could include a second UCP probe for detecting surface proteins that confer drug resistance, providing both detection and susceptibility results in one assay.
UCP nanoparticles have also been used in nonlateral flow diagnostic formats, including immunohistochemistry, microarrays, magnetic bead assays, , and plate immunoassays, though these platforms are not readily amenable to low-resource, point-of-care settings. Even in the lateral flow format, UCP nanoparticles present interesting challenges for field deployment. Clearly, sample preparation methods, including purification, concentration, and amplification, must be adapted for environments lacking controlled laboratory conditions and should rely on as little electricity as possible.
While hand-powered centrifuges , and battery-powered mixers , have been developed, the ideal POC assay will be optimized to preclude these additional resources. Another issue, often unaddressed, is that the lateral flow strips must be completely dry before optical measurements and analysis. This is because water also absorbs in the near-IR, decreasing excitation efficiency of the sensitizer. Finally, detection of UCP particles relies on optical instrumentation. Many of the sample preparation methods described in section 3 can be applied to UCP lateral flow formats.
Additionally, innovations in hand-held optical readers discussed in section 5 require only simple adaptations to detect the anti-Stokes shift of UCP particles. There are clear advantages of using UCP nanoparticles as labels in lateral flow assays, including their inherently low background interference and high analytical sensitivity. Innovations in sample preparation methods and the development of portable optical readers will allow for these advantages to be exploited in low-resource, POC settings.
While most frequently used for sample preparation and biomarker enrichment, magnetic nanoparticles are emerging as promising labels in POC assays. Similar to noble metal nanoparticles, magnetic nanoparticles can be easily functionalized and possess strong optical absorbance, which has led to their use as visual labels on lateral flow assays. In contrast, magnetization measurements can be performed regardless of the opacity of the substrate, taking advantage of the entire volume of the test line on a lateral flow assay.
The properties of magnetic particles are size- and temperature-dependent. In the bulk, these materials are ferri- or ferromagnetic and thus retain magnetization after an external field has been applied. This hysteresis reaches a maximum when particle size is decreased to the point that the material becomes single-domain.
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As particle size is even further reduced, the hysteresis effect decreases until the particles reach a critical diameter, below which Brownian forces are strong enough to overcome magnetic forces. Thus, at these small sizes, the particles are superparamagnetic; the magnetic moments of the particles are aligned in the presence of an external magnetic field, but they revert back to a nonmagnetic state when the field is removed. In the lateral flow format, magnetic nanoparticles are labeled with target-specific molecular recognition elements and employed as conjugates for analyte detection.
In the absence of magnetic particles, the net current induced in the coils is zero. However, when particles are present, the direction of their magnetic moments oscillates with the external magnetic field, resulting in a measurable net voltage induced across the coils that is proportional to the total number of particles at the test or control line. Magnetoresistive sensors are placed close enough to the particles to detect the fringe field they produce based on the change in resistance of the materials within the sensor.
General format of an inductive sensor for the detection of magnetic nanoparticles on lateral flow assays. Magnetic nanoparticles have been employed as detection labels in lateral flow assays for protein and whole-cell targets. For example, Handali et al. When contaminated, undercooked pork is ingested, the parasites develop into tapeworms in the human gut taeniasis.
However, if eggs are ingested, the larval stage can infect the human nervous system, potentially forming cysts in the brain. This severe form of the disease, called neurocysticercosis, is a leading cause of epilepsy worldwide. Diagnosis of neurocysticercosis currently requires CT scans of the brain, a technology that is unavailable in low-resource settings. Handali et al. The recombinant antigen at the test line and the antigen conjugated to magnetic particles were able to simultaneously bind to host antibodies in the sample, taking advantage of the multivalent nature of anti-ES33 and anti-T24 IgM and IgG antibodies.
Further, because the assays were not species-specific, they could be used to detect porcine cysticercosis as a marker of disease control and transmission. One disadvantage of utilizing superparamagnetic labels is that many magnetic readers are benchtop devices requiring electricity and a laboratory setting. As hand-held magnetic readers become more commonplace, these assays will become truly impactful. Superparamagnetic lateral flow assay for A taeniasis and B neurocysticercosis. The top image shows visual signal on lateral flow strips.
Below are signal read-outs from negative middle and positive bottom strips using induction-based magnetic assay reader. Figure adapted with permission from ref Copyright American Society for Microbiology. In addition to T. However, current instrumentation, which will be discussed further in section 5.
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One exciting avenue that has yet to be explored for infectious disease detection is the employment of the same superparamagnetic nanoparticles for dual purposes: immunomagnetic biomarker enrichment from large-volume samples and visual labeling for lateral flow assays. Ideally, such a diagnostic would integrate sample preparation and assay into one device. Once developed, the combined effects of target enrichment and magnetic detection could lead to a highly sensitive test capable of detecting low-density infections.
One of the most widely utilized techniques for improving the sensitivity of diagnostics is signal amplification, where thousands of signaling molecules are generated for every one biomarker molecule. Though there are now numerous methods for amplifying signal in diagnostic assays, the use of metalloenzymes was one of the first approaches. The high catalytic efficiencies of these enzymes enable the rapid conversion of substrate to detectable products. The three primary enzymes used in metalloenzyme detection conjugates rely on different metal ions for catalytic activity.
Catalase, on the other hand, simply catalyzes the disproportionation of H 2 O 2. Metalloenzyme-antibody conjugates have been widely implemented in ELISAs for the detection of protein biomarkers for disease. This is due to the sensitivity afforded by the use of enzymes for signal amplification as well as the specificity of the antibody—antigen interactions used for molecular recognition.
Lastly, the lack of thermal and long-term stability of metalloenzymes in ELISAs can lead to suboptimal assay performance, as ELISAs are intrinsically dependent on these metalloenzymes for signal amplification and readout. To mitigate these issues, investigators have begun to use paper as the ELISA solid support, increasing the likelihood that these sensitive assays could be used in resource-limited settings.
Cheng et al. Samples containing biomarker were added to the paper ELISA card, which was placed on top of a blotting pad to enable wicking of the reagents through the test wells. Lathwal and Sikes conducted a systematic investigation of several signal amplification methods for paper-based colorimetric detection of malarial biomarker HRP2. Because all factors i. Systematic evaluation of various signal amplification methods for detection of malarial biomarker HRP2.
Positive control samples shown in A contained HRP2, whereas negative control samples shown in B did not. The optimal time window for signal readout could be determined for each method, where the positive controls demonstrated detectable visual signal while the negative controls showed no detectable signal. The advantages of paper-based ELISAs are potentially compromised by the instability of metalloenzyme conjugates, since denaturation of metalloenzymes leads to poor turnover of substrate and lower sensitivities.
This assay also demonstrated the utility of metalloenzymes in paper-based POC diagnostics, providing a signal amplification step that is rarely present in conventional paper diagnostics e. These advances in enzyme stabilization when combined with simplified paper-based assay formats could potentially allow for ELISA sensitivity to be translated for direct use at the point of care.
The integration of noble metal nanoparticles has further augmented the signal amplification capabilities of metalloenzymes in infectious disease diagnostics. Nanoparticles have served as surfaces for the coupling of antibody-metalloenzyme conjugates and have been implemented in electrochemical sensors for detection of infectious disease-associated protein biomarkers. A glassy carbon electrode was modified with gold nanoparticles to allow for immobilization of anti-p24 capture antibodies.
HRP-conjugated anti-p24 antibodies were used for detection, catalyzing the oxidation of substrate hydroquinone in the presence of H 2 O 2.
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The reaction generated a reductive current at the electrode surface proportional to p24 concentration. While the assay was robust to human serum samples spiked with p24, the serum samples tested contained a p24 concentration 3 orders of magnitude higher than the LOD. Nonetheless, this amperometric method demonstrated the value of integrating noble metal nanoparticles with metalloenzyme conjugates for signal amplification in diagnosis of infectious diseases.
Noble metal nanoparticles have also been utilized as colorimetric signaling probes in ELISAs for detection of protein biomarkers for disease. However, as opposed to using conventional metalloenzyme substrates for colorimetric detection, plasmonic ELISAs employ the enzyme as a kinetic tool for nanoparticle nucleation. This causes drastic shifts in SPR and in the absorbance spectra of the nanoparticles that are detectable with the naked eye.
When p24 was present in a sample, the catalase-conjugated detection antibody was also present and catalyzed H 2 O 2 disproportionation. The red-shift in the SPR was highly sensitive toward H 2 O 2 concentration; thus, depletion of H 2 O 2 with catalase that was only present in ppositive samples allowed for very sensitive detection of p24 with the naked eye. The absorbance was also quantified using a simple spectrophotometric readout, yielding a detection limit of 1. It would permit earlier detection of p24, leading to improved outcomes for HIV patients.
The assay could be particularly impactful for the challenges associated with early infant HIV diagnosis in low-resource settings. The plasmonic ELISA presented by the authors still calls for extensive sample handling and user manipulation and is currently unsuitable to a primary healthcare setting. Adaptation of the previously discussed enzyme stabilization measures and integration of the assay to a field-ready format e. In positive samples, antibody-conjugated catalase depleted H 2 O 2 , causing a shift in SPR and absorbance of AuNPs from red to blue that is proportional to p24 concentration.
B Naked eye detection of p The visual data demonstrated that the assay was specific for p24 versus a control protein BSA. Copyright Springer Nature. Metalloenzymes play a critical role for signal amplification in a number of assays, enabling the sensitive detection of infectious diseases. Several research efforts have been aimed at translating the sensitivity of metalloenzyme-based assays to formats such as paper-based diagnostics that are amenable to resource-limited settings. There are numerous methods that utilize nonenzymatic means for signal amplification that eliminate the issue of long-term enzyme storage altogether, including nanoparticles that act as enzyme mimics and other metal-based methods.
These will be covered in the following section. While the majority of signal amplification in bioassays is enzyme-based, several interesting metal-based amplification strategies have been developed. These strategies include metal nanoparticle dissolution, nanocrystal ion exchange, enzyme mimics, and reductive nanoparticle enlargement. However, many of these strategies suffer from the following drawbacks: 1 amplification often requires additional steps to be integrated into point-of-care test workflow, and 2 incorporation into a paper-based format can be technically challenging.
However, innovative assay design can overcome these challenges. Integration of signal amplification into point-of-care tests can drastically improve analytical and diagnostic sensitivity, resulting in earlier diagnoses and detection of low-density infections. Therefore, diagnostics which incorporate novel and user-friendly signal amplification steps could fill a need for elimination campaigns and surveillance programs. This section reviews metal-based signal amplification strategies that show promise for application to low-resource infectious disease diagnostics.
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At the heart of signal amplification is the principle that, for each biomarker target captured in an assay, many signal-generating elements particles, molecules, atoms, electrons, photons, etc. In a typical nanoparticle-based assay, a single nanoparticle often indicates the presence of one biomolecule. Principles of signal amplification by A nanoparticle dissolution and B nanocrystal cation exchange. Images adapted from refs and Copyright and , respectively, American Chemical Society. Metal ion chelating reagents that result in chromogenic or fluorescent signal have long been used for detection of trace metals for a myriad of applications.
After functionalized iron-oxide particles bound to the target, the nanocrystals were treated with acid and reducing agents, resulting in stoichiometric conversion to ferrous ions. When excess ferrozine was added, solutions changed from transparent to purple upon chelation, with intensities directly proportional to the iron concentration in solution. Proof-of-concept assays detecting mouse IgG had low picomolar detection limits, similar to assays that depend on enzymatic signal amplification.
To extend the applicability of their amplification technology, the group also demonstrated its use in a Western blot. By switching the chelating reagent to potassium ferrocyanide Prussian blue , the reagent could easily be precipitated onto a cellulose membrane when iron oxide particles were used as detection elements. Another avenue for signal amplification similar to nanoparticle dissolution is nanocrystal cation exchange, in which the cations within a nanocrystal are place-exchanged with different cations. Despite this versatility, the cation exchange method has yet to be applied in paper-based formats.
Similar to the ILISA example discussed previously, signal amplification using nanocrystal cation exchange would require a precipitating reagent for metal ion detection as well as clever design of a paper microfluidic device. Enzymatic signal amplification results in high analytical sensitivity and is easily performed in a controlled laboratory environment. However, as discussed in section 4. In recent years, some inorganic nanoparticles, including noble metal, rare earth, and magnetic nanoparticles, have been found to display surprising enzyme-like catalytic activity.
Further, catalytic activity of inorganic nanoparticles can be tuned with particle size, shape, coating, modification, and composition. For these reasons, nanozymes have been incorporated into a myriad of sensors for various applications. In , Gao et al. Fe 3 O 4 magnetic nanoparticles were found to catalytically turn over several common horseradish peroxidase substrates, including TMB, DAB, and o -phenylenediamine OPD , with catalytic turnover numbers equal to or improved over horseradish peroxidase.
The group demonstrated that the particles could be used in place of horseradish peroxidase in a traditional immunoassay and that the magnetic properties of Fe 3 O 4 could be leveraged further to enrich biomarkers before detection. Incorporation of this detection scheme, as well as careful and systematic design of the affinity reagents for p24 capture and detection, resulted in a lateral flow assay with femtomolar detection limits, more sensitive than laboratory-based ELISA methods and nearly 2 orders of magnitude more sensitive than commercially available rapid tests.
The advantages of the nanoparticle enzyme mimics were directly demonstrated in a stability test in which the activities of lyophilized porous Pt core—shell nanocatalyst conjugate and lyophilized HRP conjugates were measured over time. Format and signal amplification strategy of the ultrasensitive HIV p24 lateral flow assay developed by Loynachan et al. Figure adapted from ref To achieve such significant improvements in sensitivity using nanozymes, a wash step, a substrate addition step, and a reaction quenching step were inserted into the lateral flow assay workflow after the initial signal development.
Redesigned paper devices or automated lateral flow cassettes could simplify this workflow and allow for application of nanozymes in field settings, providing much-needed signal amplification and improved sensitivity for low-resource infectious disease diagnostics. The use of gold nanoparticles as detection elements in commercially available lateral flow assays is ubiquitous.
One simple solution for improving sensitivity is chemically enlarging the particles, making them more visually intense. In this process, a lateral flow assay is run in the typical manner such that, if the antigen is present, a gold nanoparticle-containing sandwich complex is formed at the test line. Next, an enhancement solution consisting of a molecular precursor and reducing agent is added to the test.
The gold nanoparticles at the test and control lines serve as nucleation sites for solid metal deposition. The most common format for particle enlargement, silver enhancement, is based on 19th-century photographic techniques and involves the reduction of silver ions e. Silver enhancement of gold nanoparticles at the test line of a lateral flow assay. This enhancement reaction was performed in an automated cassette developed by Fujifilm.
Because silver enhancement found its first biological application in tissue staining in , there are many commercially available silver enhancement solutions designated for microscopy applications Sigma, Thermo, Ted Pella, Nano, etc. The first application of silver enhancement to paper diagnostics was in when Horton et al. One of the drawbacks to silver enhancement on lateral flow assays is that it must be performed after the test has completed its initial development.
Increasing the total number of steps required reduces the likelihood that the test could be applied in the field. For example, one group found that silver enhancement improved the detection limits of their Y. In order to take advantage of this impressive enhancement, the authors allowed the gold test to develop as usual, washed the strip three times, submerged it into enhancing reagents for 5 min, and then stopped the reaction with sodium thiosulfate. This procedure is feasible in a district hospital or even a local health outpost with minimal resources, and the enhanced assay would be a true asset in these settings should a plague pandemic occur.
However, the additional steps required for signal amplification make POC application in a low-resource field setting unlikely. For this reason, some groups who employ a silver enhancement step in their paper diagnostic assays have moved away from the traditional lateral flow assay format and toward alternative formats that allow for automated delivery of silver enhancement reagents to the test line. Fujifilm , applied their expertise in photo technology to develop a benchtop workstation that automated silver enhancement for influenza rapid diagnostic tests.
In this format, a user added the sample to a lateral flow cartridge that contained all reagents necessary for test washing and silver enhancement. The cartridge was inserted into the benchtop workstation, which released the solutions in a timed, automated manner and provided a quantitative readout of the strip after test development was completed.
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Despite the fact that the instrument greatly simplified the assay protocol for the user, the requirement of a reliable source of electricity greatly inhibits its application to a field setting. Recently, the Yager and Fu groups have designed 2DPNs that rely on unique paper geometry or embedded paper-fluidic valves to enable programmed, electricity-free delivery of silver enhancement reagents to the assay test line.
The unique physical structures of 2DPNs allow for precisely timed delivery of sample, then gold conjugate, and finally silver enhancement reagents to the test line. Similarly, Cho et al. The enhancement reagents flowed perpendicular to the initial immunochromatographic test over the test and control lines. These creative approaches to redesigning the lateral flow assay make silver enhancement the most field-deployable metal-based signal amplification strategy to date, although large-scale manufacturing requirements must be considered to determine the scalability of such test designs.
Finally, it should be noted that while silver enhancement on gold particles is most common, other metals have been used for reductive nanoparticle enlargement for lateral flow enhancement. The amplification methods discussed thus far increase the number of signaling elements after the initial assay has developed, requiring additional steps post hoc.
Another amplification strategy is to generate a greater number of detectable molecules midassay, thereby increasing the downstream signal output of the assay. In , the Mirkin group demonstrated that protein biomarker targets could be detected indirectly in a highly sensitive manner by employing gold nanoparticles functionalized with DNA tags. In this strategy, magnetic microparticles functionalized with target-specific antibodies were added to a biological sample. After biomarker capture, the supernatant was removed and intermediate detection elements were added to the particles.
These detection elements consisted of gold nanoparticles functionalized with a low density of target-specific antibodies and a very high density of double-stranded barcode DNA. One powerful advantage of this modular assay format is it could be easily multiplexed, with distinct barcode tags for each target of interest. Workflow of biobarcode assay for protein detection. Copyright American Association for the Advancement of Science. Since its development, the biobarcode assay format has been utilized for the detection of infectious diseases such as hepatitis B, hepatitis C, , variola virus, Ebola, HIV, , , B.
Initial detection strategies for the biobarcode assay were scanometric; the barcode tags were detected in a sandwich hybridization assay on the surface of a glass slide, with gold nanoparticles as the detection elements. Signal was further enhanced using reductive silver deposition before the slides were evaluated using image analysis. Nam et al. The hybridization of the biobarcode tags with complementary DNA resulted in aggregation of the two gold nanoparticle-DNA conjugates, yielding a detectable color change.
None of these detection methods can be employed in a field setting; however, it is not difficult to imagine developing a hybridization-based lateral flow assay for barcode tag detection or functionalizing the tags themselves with moieties such as biotin or a FLAG peptide that could make them readily detectable in a paper diagnostic format. As is evidenced by sections 4. However, even with the advancements in metalloenzyme stabilization and highly stable nanoparticle-based approaches, POC assays utilizing signal amplification are still scarce. Most of the assays discussed, even those that employ paper substrates or lateral flow formats, require too many user steps before the signal is generated.
Future work that minimizes user steps, for instance, through use of 2DPNs or vertical flow assay formats, will be critical in translating these signal amplification strategies from laboratory tests to assays that can be run at a primary healthcare facility. Moreover, most of the assays discussed in sections 4. The next section will discuss the various types of field-deployable instrumentation that have been developed in an effort to bring quantitative and sensitive assays, such as those discussed in section 4 , to low-resource settings. Traditionally, point-of-care diagnostics such as lateral flow assays have delivered qualitative visual results.
Although this simplicity is advantageous in the field, the diagnostic sensitivity and specificity can suffer from subjective interpretation and user bias errors. Quantitative measurements mitigate these factors, avoiding the data loss associated with qualitative tests and providing insight into important variables such as infection intensities and biomarker expression patterns. In an elimination setting, these parameters allow for robust epidemiological studies into transmission dynamics and intervention efficacy.
Novel detection strategies that offer highly sensitive and quantitative results, including many of those outlined in section 4 , require instrumentation for signal readout. As a result, the development of appropriate and simple instrumentation will likely become an integral part of the application of diagnostic technologies in low-resource settings. Additionally, many instruments incorporate common consumer electronic devices, such as mobile phones and smart phones, thereby reducing the equipment burden.
This section outlines some of the devices developed for point-of-care infectious disease diagnosis. Table 3 is included at the beginning of section 5 to highlight selected examples of point-of-care instrumentation.
A vast majority of the metal-based probes and nanoparticles highlighted in section 4 produce optical signals such as absorbance, fluorescence, or phosphorescence. As a result, a diverse array of instrumentation has been developed to facilitate assay readout for imaging and quantitative purposes. This section provides an overview of efforts to develop portable, affordable, and sensitive instruments for optical detection in low-resource settings.
Conventional microscopy remains the gold standard diagnostic technique for many infectious diseases, including malaria, tuberculosis, schistosomiasis, and intestinal protozoa. While microscopy can be a useful diagnostic tool, results depend strongly on infection intensities, sample preparation methods, and the training level of the microscopist. Additionally, microscope instrumentation can be expensive and bulky. To address these drawbacks, many groups are developing portable, affordable, and easy-to-use microscopy tools suitable for low-resource settings. While this solution does not address some of the primary disadvantages of microscopy as a POC diagnostic i.
Such devices typically replace high-energy, expensive light sources with LEDs, reducing the expense and power required for illumination in addition to increasing the light source lifetime. The diagnostic utility of the microscope was demonstrated in a small field trial for detection of M.
When samples were evaluated as positive or negative for M. Examples of microscopy instrumentation developed for use in low-resource settings. Copyright Miller et al. B Layout of an assembled Foldscope. Copyright Cybulski et al. C Reverse-lens CellScope mobile phone attachment for diagnosis of schistosomiasis and intestinal protozoa.
Copyright Coulibaly et al. D Mobile phone-based LoaScope. This example demonstrates the importance of rigorous field evaluation of novel diagnostic devices and indicates that improvements to the Foldscope must be made before implementation for case management.
Recently, mobile phone-based microscopy has emerged as a potential alternative to conventional microscopes for infectious disease diagnostics. Additionally, the acquisition of digital images could allow for image-processing locally or remotely , automated diagnoses, and near real-time data transmission. These advantages, coupled with disease-specific software applications, could potentially decrease the user variability typically associated with microscopy, improving case management and epidemiological studies.
An application downloaded to the smartphone is used for stage control, video capture, image analysis, and data reporting of quantitative L. Detection of L. These adverse events have led to the suspension of mass drug administration campaigns and subsequent major setbacks in onchocerciasis and LF elimination efforts. Rapid, point-of-care measurement of L. This device was validated in a field setting and yielded results similar to those of thick smears. This is a striking example of mobile phone-based microscopy in the field; all LoaScope measurements were performed by operators with only one hour of training, and the application-specific software significantly decreased the probability of user error by eliminating the need for subjective interpretation of results.
In total, the LoaScope enabled ivermectin delivery to participants that otherwise would not have received treatment for onchocerciasis, demonstrating the incredible impact mobile phone microscopy can have when applied to detection of infectious diseases. Despite the fact that many mobile phone-based microscopes lack the analytical and diagnostic sensitivity of conventional microscopes, the LoaScope is an excellent demonstration that mobile phone microscopy can be highly impactful if applied in an appropriate use-case scenario.
Because this particular study focused on identifying patients with very high L. Generalization of this technology to other filarial diseases will also require further study. Additionally, potential interference from other filarial parasites needs to be studied. Rare earth complexes containing solely inorganic donor ligands are surveyed with main emphasis on oxygen-donor ligands, especially the oxoanions.
As examples, the sulfato and nitrato complexes are discussed in more detail. The role of water molecules as ligands and hydrogen bond donors is included in the discussion. Although solid state structure and properties are emphasized, a brief comparison to results obtained in solution is also made. Unable to display preview. Download preview PDF.
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