All-printed nanophotonic biochip for point-of-care testing of biomarkers.
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ABSTRACT:
SUBMITTER: Chi J
PROVIDER: S-EPMC9033290 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Publications
All-printed nanophotonic biochip for point-of-care testing of biomarkers.
Chi Jimei J Wu Dongdong D Su Meng M Song Yanlin Y
Science bulletin 20220422 12
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Project description:Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world.
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Project description:Rapid, accurate, and noninvasive detection of biomarkers in saliva, urine, or nasal fluid is essential for the identification, early diagnosis, and monitoring of cancer, organ failure, transplant rejection, vascular diseases, autoimmune disorders, and infectious diseases. We report the development of an Immuno-CRISPR-based lateral flow assay (LFA) using antibody-DNA barcode complexes with magnetic enrichment of the target urinary biomarkers CXCL9 and CXCL10 for naked eye detection (ImmunoMag-CRISPR LFA). An intermediate approach involving a magnetic bead-based Immuno-CRISPR assay (ImmunoMag-CRISPR) resulted in a limit of detection (LOD) of 0.6 pg/mL for CXCL9. This value surpasses the detection limits achieved by previously reported assays. The highly sensitive detection method was then re-engineered into an LFA format with an LOD of 18 pg/mL for CXCL9, thereby enabling noninvasive early detection of acute kidney transplant rejection. The ImmunoMag-CRISPR LFA was tested on 42 clinical urine samples from kidney transplant recipients, and the assay could determine 11 positive and 31 negative urinary samples through a simple visual comparison of the test line and the control line of the LFA strip. The LFA system was then expanded to quantify the CXCL9 and CXCL10 levels in clinical urine samples from images. This approach has the potential to be extended to a wide range of point-of-care tests for highly sensitive biomarker detection.
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Project description:BackgroundPertussis is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis (B. pertussis). The infection is difficult to diagnose especially in underserved or resource-limited areas. We developed a low-cost and instrument-free diagnostic method for rapid and accurate detection of B. pertussis on a point-of-care (POC) testing device.MethodsWe developed a paper/polymer hybrid microfluidic biochip integrated with loop-mediated isothermal amplification (LAMP) method for the rapid and accurate detection of B. pertussis. This microfluidic approach was validated by testing 100 de-identified remnant clinical nasopharyngeal swabs and aspirates, which were confirmed to be either positive or negative for B. pertussis by a validated real-time PCR assay at the Children's Hospital Los Angeles.FindingsThe instrument-free detection results could be successfully read by the naked eye within 45 min with a limit of detection (LOD) of 5 DNA copies per well. Our optimized bacterial lysis protocol allowed the direct testing of clinical samples without any complicated sample processing/preparation (i.e. DNA extraction) or the use of any equipment (e.g. centrifuges). The validation of the microfluidic approach was accomplished by testing 100 clinical samples. High sensitivity (100%) and specificity (96%) with respect to real-time PCR were achieved.InterpretationThis microfluidic biochip shows great potential for point-of-care disease diagnosis in various venues including schools and physician's offices, especially in low-resource settings in developing nations.FundingNIH/NIAID under award number R21AI107415, NIH RCMI Pilot Grant, the Philadelphia Foundation, the Medical Center of the Americas Foundation.
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Project description:Multiplexed point-of-care testing (xPOCT), which is simultaneous on-site detection of different analytes from a single specimen, has recently gained increasing importance for clinical diagnostics, with emerging applications in resource-limited settings (such as in the developing world, in doctors' offices, or directly at home). Nevertheless, only single-analyte approaches are typically considered as the major paradigm in many reviews of point-of-care testing. Here, we comprehensively review the present diagnostic systems and techniques for xPOCT applications. Different multiplexing technologies (e.g., bead- or array-based systems) are considered along with their detection methods (e.g., electrochemical or optical). We also address the unmet needs and challenges of xPOCT. Finally, we critically summarize the in-field applicability and the future perspectives of the presented approaches.
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Project description:Sepsis, a potentially life-threatening complication of an infection, has the highest burden of death and medical expenses in hospitals worldwide. Leukocyte count and CD64 expression on neutrophils (nCD64) are known to correlate strongly with improved sensitivity and specificity of sepsis diagnosis at its onset. A major challenge is the lack of a rapid and accurate point-of-care (PoC) device that can perform these measurements from a minute blood sample. Here, we report a PoC microfluidic biochip to enumerate leukocytes and quantify nCD64 levels from 10 μl of whole blood without any manual processing. Biochip measurements have shown excellent correlation with the results from flow cytometer. In clinical studies, we have used PoC biochip to monitor leukocyte counts and nCD64 levels from patients' blood at different times of their stay in the hospital. Furthermore, we have shown the biochip's utility for improved sepsis diagnosis by combining these measurements with electronic medical record (EMR).
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Project description:3D printing has been an emerging fabrication tool in prototyping and manufacturing. We demonstrated a 3D microfluidic simulation guided computer design and 3D printer prototyping for quick turnaround development of microfluidic 3D mixers, which allows fast self-mixing of reagents with blood through capillary force. Combined with smartphone, the point-of-care diagnosis of anemia from finger-prick blood has been successfully implemented and showed consistent results with clinical measurements. Capable of 3D fabrication flexibility and smartphone compatibility, this work presents a novel diagnostic strategy for advancing personalized medicine and mobile healthcare.
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Project description: Not available
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Project description:BackgroundSouth Africa, with the highest burden of HIV infection globally, has made huge strides in its HIV/ART programme, but AIDS deaths have not decreased proportionally to ART uptake. Advanced HIV disease (CD4 < 200 cells/mm3) persists, and CD4 count testing is being overlooked since universal test-and-treat was implemented. Point-of-care CD4 testing could address this gap and assure differentiated care to these vulnerable patients with low CD4 counts.MethodsA time randomised implementation trial was conducted, enrolling 603 HIV positive non-ART, not pregnant patients at a primary health care clinic in Durban, South Africa. Weeks were randomised to either point-of-care CD4 testing (n = 305 patients) or standard-of-care central laboratory CD4 testing (n = 298 patients) to assess the proportion initiating ART at 3 months. Cox regression, with robust standard errors adjusting for clustering by week, were used to assess the relationship between treatment initiation and arm.ResultsAmong the 578 (299 point-of-care and 279 standard-of-care) patients eligible for analysis, there was no significant difference in the number of eligible patients initiating ART within 3 months in the point-of-care (73%) and the standard-of-care (68%) groups (P = 0.112). The time-to-treat analysis was not significantly different in patients with CD4 counts of 201-500 cells/mm3 which could have been due to appointment scheduling to cope with the large burden of cases. However, in patients with advanced HIV disease (CD4 < 200cells/mm3) 65% more patients started ART earlier in the point-of-care group (HR 1.65 (95% confidence interval (CI) = 0.99-2.75; P = 0.052) compared to the standard-of-care group.ConclusionsPoint-of-care testing decreased time-to-treatment in those with advanced HIV disease. With universal test and treat for HIV, rollout of simple point-of-care CD4 testing would ensure early diagnosis of advanced HIV disease and facilitate differentiated care for these vulnerable patients as per the World Health Organisation 2020 target product profile for point-of-care CD4 testing.Trial registrationISRCTN14220457.
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Project description:With the growing number of patients suffering from noninfectious chronic diseases, the consumption of point of care testing strips increases exponentially, particularly blood glucose testing strips, causing an increasingly severe conflict between strip recycling and the environment. In this paper, fully transient electrochemical strips are developed as a substitute for non-degradable strips. Proper explorations were made, including finding out suitable degradable substrates for strip-making among different degradable materials and optimization of degradable conducting paste. Taking advantage of dissolvable polymer-based materials and nontoxic carbon materials, the transient strips have validated electrochemical functionality to determine physiological levels of glucose with a sensitivity of 14.33 μA mM-1 cm-2 (correlation coefficient R 2 is 0.99498) and reached full-degradation within a week after disposal. The interference experiment (negligible interference current response under 7%) and recovery tests (recovery ratio ranging from 92.46% to 102.47%) have illustrated its practical application in real sample detection. Such degradable-characterized testing strips can be widely used in chronic disease management with daily eco-friendly point of care testing, without potential pollution to the environment.
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