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1.
Anal Chem ; 94(49): 17102-17111, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36454606

ABSTRACT

Diagnostic assays are commonly performed in multiple steps, where reagents are added at specific times and concentrations into a reaction chamber. The reagents require storage, preparation, and addition in the correct sequence and amount. These steps rely on trained technicians and instrumentation to perform each task. The reliance on such resources hinders the use of these diagnostic assays by lay users. We developed a tablet that can sequentially introduce prequantified lyophilized diagnostic reagents at specific time points for a multistep assay. We designed the tablet to have multiple layers using cellulose-grade polymers, such as microcrystalline cellulose and hydroxypropyl cellulose. Our formulation allows each layer to dissolve at a controlled rate to introduce reagents into the solution sequentially. The release rate is controlled by modulating the compression force or chemical formulation of the layer. Controlling the reagent release time is important because different assays have specific times when reagents need to be added. As proof of concept, we demonstrated two different assays with our tablet system. Our tablet detected nucleic acid target (tpp47 gene from Treponema pallidum) and nitrite ions in an aqueous sample without user intervention. Our multilayer tablets can simplify multistep assay processes.


Subject(s)
Indicators and Reagents , Tablets/chemistry , Delayed-Action Preparations/chemistry , Solubility
2.
ACS Nanosci Au ; 2(4): 324-332, 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35996437

ABSTRACT

Current urinary tract infection (UTI) diagnostic methods are slow or provide limited information, resulting in prescribing antibiotic therapy before bacterial pathogen identification. Here, we adapted a gold nanoparticle colorimetric approach and developed a smartphone platform for UTI detection. We show the parallel identification of five major UTI pathogens at clinically relevant concentrations of 105 bacteria/mL using bacteria-specific and universal probes. We validated the diagnostic technology using 115 positive and 19 negative samples from patients with Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae infections. The assay successfully identified the infecting pathogen (specificity: >98% and sensitivity: 51-73%) in 3 h. Our platform is faster than culturing and can wirelessly store and transmit results at the cost of $0.38 per assay.

3.
Nano Lett ; 21(12): 5209-5216, 2021 06 23.
Article in English | MEDLINE | ID: mdl-34110166

ABSTRACT

The ability to rapidly diagnose, track, and disseminate information for SARS-CoV-2 is critical to minimize its spread. Here, we engineered a portable smartphone-based quantum barcode serological assay device for real-time surveillance of patients infected with SARS-CoV-2. Our device achieved a clinical sensitivity of 90% and specificity of 100% for SARS-CoV-2, as compared to 34% and 100%, respectively, for lateral flow assays in a head-to-head comparison. The lateral flow assay misdiagnosed ∼2 out of 3 SARS-CoV-2 positive patients. Our quantum dot barcode device has ∼3 times greater clinical sensitivity because it is ∼140 times more analytically sensitive than lateral flow assays. Our device can diagnose SARS-CoV-2 at different sampling dates and infectious severity. We developed a databasing app to provide instantaneous results to inform patients, physicians, and public health agencies. This assay and device enable real-time surveillance of SARS-CoV-2 seroprevalence and potential immunity.


Subject(s)
COVID-19 , Quantum Dots , Humans , Immunoassay , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies , Smartphone
4.
ACS Nano ; 14(4): 3822-3835, 2020 04 28.
Article in English | MEDLINE | ID: mdl-32223179

ABSTRACT

COVID-19 has spread globally since its discovery in Hubei province, China in December 2019. A combination of computed tomography imaging, whole genome sequencing, and electron microscopy were initially used to screen and identify SARS-CoV-2, the viral etiology of COVID-19. The aim of this review article is to inform the audience of diagnostic and surveillance technologies for SARS-CoV-2 and their performance characteristics. We describe point-of-care diagnostics that are on the horizon and encourage academics to advance their technologies beyond conception. Developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak would be useful in preventing future epidemics.


Subject(s)
Betacoronavirus/pathogenicity , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Point-of-Care Testing , Smartphone , COVID-19 , COVID-19 Testing , Humans , Mobile Applications , Nucleic Acid Amplification Techniques , Pandemics , Population Surveillance , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed , Viral Proteins/analysis
5.
Proc Natl Acad Sci U S A ; 117(9): 4632-4641, 2020 03 03.
Article in English | MEDLINE | ID: mdl-32071225

ABSTRACT

Point-of-care diagnostic assays often involve multistep reactions, requiring a wide range of precise temperatures. Although precise heating is critical to performing these assays, it is challenging to provide it in an electricity-free format away from established infrastructure. Chemical heaters are electricity-free and use exothermic reactions. However, they are unsuitable for point-of-care multistep reactions because they sacrifice portability, have a narrow range of achievable temperatures, and long ramp-up times. Here we developed a miniature heater by modulating the lithium-water reaction kinetics using bubbles in a channel. Our heaters are up to 8,000 times smaller than current devices and can provide precise (within 5 °C) and tunable heating from 37 °C to 65 °C (∆TRT = 12 °C to 40 °C) with ramp-up times of a minute. We demonstrate field portablity and stability and show their use in an electricity-free multistep workflow that needs a range of temperatures. Ultimately, we envision providing better access to cutting edge biochemical techniques, including diagnostics, by making portable and electricity-free heating available at any location.

6.
J Am Chem Soc ; 139(48): 17341-17349, 2017 12 06.
Article in English | MEDLINE | ID: mdl-29172470

ABSTRACT

Medical diagnostic assays provide exquisite sensitivity and precision in the diagnoses of patients. However, these technologies often require multiple steps, skilled technicians, and facilities to store heat-sensitive reagents. Here, we developed a high-throughput compression method to incorporate different assay components into color-coded tablets. With our technique, premeasured quantities of reagents can be encapsulated in compressed tablets. We show that tableting stabilizes heat-sensitive reagents and simplifies a broad range of assays, including isothermal nucleic acid amplification techniques, enzyme-based immunoassays, and microbead diagnostics. To test the clinical readiness of this tableting technology, we show the ability of tableted diagnostics for screening hepatitis B-positive patient samples. Our development simplifies complicated assays and the transportation of reagents and mitigates the need for refrigeration of reagents. This advances the use of complex assays in remote areas with limited infrastructure.

7.
ACS Nano ; 11(3): 2313-2381, 2017 03 28.
Article in English | MEDLINE | ID: mdl-28290206

ABSTRACT

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.


Subject(s)
Drug Delivery Systems , Nanomedicine , Nanoparticles/chemistry , Neoplasms/drug therapy , Animals , Drug Carriers/chemistry , Humans , Nanotechnology , Neoplasms/pathology , Particle Size
8.
ACS Nano ; 10(9): 8139-42, 2016 09 27.
Article in English | MEDLINE | ID: mdl-27575458

ABSTRACT

We describe the current difference in reporting the performance of nanotechnology diagnostic devices between technologists and clinicians. This perspective specifies the "metrics" used to evaluate these devices and describes strategies to bridge the gap between these two communities in order to accelerate the translation from academic bench to the clinic. We use two recently published ACS Nano articles to highlight the evaluation of silicon nanowire and surface-enhanced Raman spectroscopy-breath diagnostic tests for patients afflicted with cancer and asthma. These studies represent some of the earliest studies of emerging nanotechnology devices utilizing clinical parameters to assess performance.


Subject(s)
Nanomedicine/trends , Nanotechnology , Humans , Nanowires , Neoplasms , Silicon , Spectrum Analysis, Raman
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