An ultra-low-cost smartphone octochannel spectrometer for mobile health diagnostics.

With the rapid development and proliferation of mobile devices with powerful computing power and the ability of integrating sensors into mobile devices, the potential impact of mobile health (mHealth) diagnostics on the public health is drawing researchers' attention. We developed a Smartphone Octo-channel Spectrometer (SOS) as a mHealth diagnostic tool. The SOS has nanoscale wavelength resolution, is self-illuminated from the smartphone itself, and is ultra-low cost (less than $20). A user interface controls the optical sensing parameters and precise alignment. After calibrating and testing the SOS by quantifying protein concentrations, we clinically validated the SOS by comparing the diagnostic performance of our device with that of a clinical spectrophotometer. About 180 serum samples from de-identified patients with 4 types of autoantibodies were blindly read the ELISA results. The accuracy of the SOS achieved 100% across the clinical reportable range compared with the FDA-approved instrument. Furthermore, the self-illuminated SOS only requires about half of the light intensity of the FDA-approved instrument to achieve clinical-level sensitivity. The low-energy-consumption and low-cost SOS enables point-of-care spectrophotometric sensing in low-resource areas, and can be integrated into point-of-care diagnostic systems for rapid multiplex readout and analysis at patient bedside or at home.

Analytical validation of an ultra low-cost mobile phone microplate reader for infectious disease testing.

Most mobile health (mHealth) diagnostic devices for laboratory tests only analyze one sample at a time, which is not suitable for large volume serology testing, especially in low-resource settings with shortage of health professionals. In this study, we developed an ultra-low-cost clinically-accurate mobile phone microplate reader (mReader), and clinically validated this optical device for 12 infectious disease tests. The mReader optically reads 96 samples on a microplate at one time. 771 de-identified patient samples were tested for 12 serology assays for bacterial/viral infections. The mReader and the clinical instrument blindly read and analyzed all tests in parallel. The analytical accuracy and the diagnostic performance of the mReader were evaluated across the clinical reportable categories by comparison with clinical laboratorial testing results. The mReader exhibited 97.59-99.90% analytical accuracy and <5% coefficient of variation (CV). The positive percent agreement (PPA) in all 12 tests achieved 100%, negative percent agreement (NPA) was higher than 83% except for one test (42.86%), and overall percent agreement (OPA) ranged 89.33-100%. We envision the mReader can benefit underserved areas/populations and low-resource settings in rural clinics/hospitals at a low cost (~$50 USD) with clinical-level analytical quality. It has the potential to improve health access, speed up healthcare delivery, and reduce health disparities and education disparities by providing access to a low-cost spectrophotometer.

Improving the antibody-based evaluation of autoimmune encephalitis.

OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABABR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65). In parallel, our research laboratory screened all samples for reactivity to brain sections and for anti-NMDAR using in-house CBAs. Samples with brain reactivity or positive clinical studies were examined with CBAs for a larger panel of antibodies. RESULTS: The clinical laboratory reported positive findings for NMDAR (80 samples), GAD65 (8), LGI1 (5), Caspr2 (2), and GABABR (4). Sixty-five serum samples and 32 CSF samples were indeterminate for one or more antibodies. In our research laboratory, all but 4 positive results were confirmed, 88 of 97 indeterminate results were resolved, and 15 additional samples were found positive (10 NMDAR, 1 AMPAR, 3 LGI1, and 1 Caspr2). Clinical information supported these diagnoses. Overall, informative autoantibodies were detected in 15.5% of cases. CONCLUSIONS: Standard clinical laboratory kits were specific, but some tests were insensitive and prone to indeterminate results. Screening with immunohistochemistry for reactivity to brain sections, followed by additional CBAs for cases with brain reactivity, improves the diagnostic accuracy of testing for autoimmune encephalitis.

Multifocal mantle cell lymphoma in situ in the setting of a composite lymphoma.

OBJECTIVES: Mantle cell lymphoma in situ (MCLIS) consists of immunophenotypically defined but histologically inapparent neoplastic cells restricted to narrow mantle zones, without expansion or invasion beyond the mantle zone. We report a unique case of MCLIS associated with a much more manifest nodal marginal zone lymphoma (MZL) in an inguinal lymph node, porta hepatis lymph node, and bone marrow. METHODS: Biopsies from all three locations were evaluated using standard H&E-stained sections, immunohistochemistry, flow cytometry, metaphase cytogenetics, and/or fluorescence in situ hybridization (FISH). RESULTS: This case is unique for three reasons. First, the histologically covert mantle cell lymphoma was multifocal, detected in all three locations using one or more of flow cytometry, immunohistochemistry, cytogenetics, and FISH. Second, the MCLIS was always accompanied by a more histologically dominant MZL. Third, where evaluable, it did not grow in an appreciable mantle zone distribution, presumably due to destruction of the normal nodal architecture by the neoplastic MZL cells and the resulting absence of recognizable follicles and mantle zones. CONCLUSIONS: This unique case provides new insight into the pathogenesis of MCLIS.

A cluster of primary varicella cases among healthcare workers with false-positive varicella zoster virus titers.

BACKGROUND: Five cases of primary varicella zoster virus (VZV) we re diagnosed among hospital healthcare workers (HCWs). All had complied with a pre-employment VZV screening program and had been considered immune. OBJECTIVES: To summarize the investigation of VZV among un-immunized HCWs and to provide recommendations for avoiding false-positive serologic tests. DESIGN: Risk of transmission of VZV to susceptible HCWs is minimized through serologic screening. Varicella vaccine is recommended for susceptible HCWs. A commercially available latex bead agglutination assay (LA) is widely used because it is rapid and easy to perform. LA was compared with the whole-cell varicella ELISA standardized in the Centers for Disease Control and Prevention (CDC) National Herpes Laboratory. SETTING/POPULATION: Large inner-city, tertiary-employee population. RESULTS: In a year, 5 HCWs presented with laboratory-confirmed primary varicella infection. Four had VZV exposures 2 weeks prior to presentation. All had documented positive VZV titers by LA performed at hire. None were offered VZV vaccination. The original LAs were judged false-positives. INTERVENTION/FOLLOW-UP INVESTIGATION: Fifty-three consecutive VZV LA samples from the hospital laboratory were retested at the CDC. Forty-four samples concurred. Of the remaining 9, 4 were positive by hospital LA but negative by CDC IgG ELISA. Four were equivocal by hospital LA but negative by CDC IgG ELISA and LA. One was positive by hospital LA but negative by LA and equivocal by ELISA at the CDC. CONCLUSION: LA may be prone to false-positive results and inappropriate for screening hospital HCWs.