10 research outputs found
Micro/Nano biomedical devices for point-of-care diagnosis of infectious respiratory diseases
Corona Virus Disease 2019 (COVID-19) has developed into a global pandemic in the last two years, causing significant impacts on our daily life in many countries. Rapid and accurate detection of COVID-19 is of great importance to both treatments and pandemic management. Till now, a variety of point-of-care testing (POCT) approaches devices, including nucleic acid-based test and immunological detection, have been developed and some of them has been rapidly ruled out for clinical diagnosis of COVID-19 due to the requirement of mass testing. In this review, we provide a summary and commentary on the methods and biomedical devices innovated or renovated for the quick and early diagnosis of COVID-19. In particular, some of micro and nano devices with miniaturized structures, showing outstanding analytical performances such as ultra-sensitivity, rapidness, accuracy and low cost, are discussed in this paper. We also provide our insights on the further implementation of biomedical devices using advanced micro and nano technologies to meet the demand of point-of-care diagnosis and home testing to facilitate pandemic management. In general, our paper provides a comprehensive overview of the latest advances on the POCT device for diagnosis of COVID-19, which may provide insightful knowledge for researcher to further develop novel diagnostic technologies for rapid and on-site detection of pathogens including SARS-CoV-2.Natural Environment Research Council (NERC): NE/R013349/
Genetic and phenotypic profiling of single living circulating tumour cells from patients with microfluidics
Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 nonâsmall cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction
Sensitive Interrogation of Enhancer Activity in Living Cells on a Nanoelectroporation-Probing Platform
Enhancers
involved in the upregulation of multiple oncogenes play
a fundamental role in tumorigenesis and immortalization. Exploring
the activity of enhancers in living cells has emerged as a critical
path to a deep understanding of cancer properties, further providing
important clues to targeted therapy. However, identifying enhancer
activity in living cells is challenging due to the double biological
barriers of a cell cytoplasmic membrane and a nuclear membrane, limiting
the sensitivity and responsiveness of conventional probing methods.
In this work, we developed a nanoelectroporation-probing (NP) platform,
which enables intranuclear probe delivery for sensitive interrogation
of enhancer activity in living cells. The nanoelectroporation biochip
achieved highly focused perforation of the cell cytoplasmic membrane
and brought about additional driving force to expedite the delivery
of probes into the nucleus. The probes targeting enhancer activity
(named âPH probeâ) are programmed with a cyclic amplification
strategy and enable an increase in the fluorescence signals over 100-fold
within 1 h. The platform was leveraged to detect the activity of CCAT1 enhancers (CCAT1, colon cancer-associated
transcript-1, a long noncoding RNA that functions in tumor invasion
and metastasis) in cell samples from clinical lung cancer patients,
as well as reveal the heterogeneity of enhancers among different patients.
The observations may extend the linkages between enhancers and cancer
cells while validating the robustness and reliability of the platform
for the assay of enhancer activity. This platform will be a promising
toolbox with wide applicable potential for the intranuclear study
of living cells
An Ion Concentration Polarization Microplatform for Efficient Enrichment and Analysis of <i>ctDNA</i>
Strategies for rapid, effective nucleic acid processing
hold tremendous
significance to the clinical analysis of circulating tumor DNA (ctDNA), a family of important markers indicating tumorigenesis
and metastasis. However, traditional techniques remain challenging
to achieve efficient DNA enrichment, further bringing about complicated
operation and limited detection sensitivity. Here, we developed an
ion concentration polarization microplatform that enabled highly rapid,
efficient enrichment and purification of ctDNA from
a variety of clinical samples, including serum, urine, and feces.
The platform demonstrated efficiently separating and enriching ctDNA within 30 s, with a 100-fold improvement over traditional
methods. Integrating an on-chip isothermal amplification
module, the platform further achieved 100-fold enhanced sensitivity
in ctDNA detection, which significantly eliminated
false-negative results in the serum or urine samples due to the low
abundance of ctDNA. Such a simple-designed platform
offers a user-friendly yet powerful diagnosis technique with a wide
applicability, ranging from early tumor diagnosis to infection screening
An Ion Concentration Polarization Microplatform for Efficient Enrichment and Analysis of <i>ctDNA</i>
Strategies for rapid, effective nucleic acid processing
hold tremendous
significance to the clinical analysis of circulating tumor DNA (ctDNA), a family of important markers indicating tumorigenesis
and metastasis. However, traditional techniques remain challenging
to achieve efficient DNA enrichment, further bringing about complicated
operation and limited detection sensitivity. Here, we developed an
ion concentration polarization microplatform that enabled highly rapid,
efficient enrichment and purification of ctDNA from
a variety of clinical samples, including serum, urine, and feces.
The platform demonstrated efficiently separating and enriching ctDNA within 30 s, with a 100-fold improvement over traditional
methods. Integrating an on-chip isothermal amplification
module, the platform further achieved 100-fold enhanced sensitivity
in ctDNA detection, which significantly eliminated
false-negative results in the serum or urine samples due to the low
abundance of ctDNA. Such a simple-designed platform
offers a user-friendly yet powerful diagnosis technique with a wide
applicability, ranging from early tumor diagnosis to infection screening
Low-Cost and Scalable Platform with Multiplexed Microwell Array Biochip for Rapid Diagnosis of COVID-19
Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens