4.8 Article

Analysis on the Go: Quantitation of Drugs of Abuse in Dried Urine with Digital Microfluidies and Miniature Mass Spectrometry

期刊

ANALYTICAL CHEMISTRY
卷 86, 期 12, 页码 6121-6129

出版社

AMER CHEMICAL SOC
DOI: 10.1021/ac5012969

关键词

-

资金

  1. Natural Sciences and Engineering Council of Canada (NSERC)
  2. U.S. National Science Foundation [CHE1307264]
  3. NSERC
  4. Ontario Graduate Scholarship (OGS) program
  5. Canada Research Chair (CRC) program

向作者/读者索取更多资源

We report the development of a method coupling microfluidics and a miniature mass spectrometer, applied to quantitation of drugs of abuse in urine. A custom digital microfluidic system was designed to deliver droplets of solvent to dried urine samples and then transport extracted analytes to an array of nanoelectrospray emitters for analysis. Tandem mass spectrometry (MS/MS) detection was performed using a fully autonomous 25 kg instrument. Using the new method, cocaine, benzoylecgonine, and codeine can be quantified from four samples in less than 15 mm from (dried) sample to analysis. The figures of merit for the new method suggest that it is suitable for on-site screening; for example, the limit of quantitation (LOQ) for cocaine is 40 ng/mL, which is compatible with the performance criteria for laboratory analyses established by the United Nations Office on Drugs and Crime. More importantly, the LOQ of the new method is superior to the 300 ng/mL cutoff values used by the only other portable analysis systems we are aware of (relying on immunoassays). This work serves as a proof-of-concept for integration of microfluidics with miniature mass spectrometry. The system is attractive for the quantitation of drugs of abuse from urine and, more generally, may be useful for a wide range of applications that would benefit from portable, quantitative, on-site analysis.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Oncology

MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer

Manu Prasad, Jonathan Zorea, Sankar Jagadeeshan, Avital B. Shnerb, Sooraj Mathukkada, Jebrane Bouaoud, Lucas Michon, Ofra Novoplansky, Mai Badarni, Limor Cohen, Ksenia M. Yegodayev, Sapir Tzadok, Barak Rotblat, Libor Brezina, Andreas Mock, Andy Karabajakian, Jerome Fayette, Idan Cohen, Tomer Cooks, Irit Allon, Orr Dimitstein, Benzion Joshua, Dexin Kong, Elena Voronov, Maurizio Scaltriti, Yaron Carmi, Cristina Conde-Lopez, Jochen Hess, Ina Kurth, Luc G. T. Morris, Pierre Saintigny, Moshe Elkabets

Summary: In head and neck cancer, treatment with MEK1/2 inhibitor delays tumor progression and enhances antitumor immunity of CD8(+) T cells. Sensitizing tumors to immunotherapy during MEK1/2 inhibition can eliminate tumors and induce immune memory. Prolonged treatment with MEK1/2 inhibitor may lead to immunosuppressive tumor microenvironment due to epithelial to mesenchymal transition.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

Review Biochemical Research Methods

Digital microfluidics as an emerging tool for bacterial protocols

Carine R. Nemr, Alexandros A. Sklavounos, Aaron R. Wheeler, Shana O. Kelley

Summary: Bacteria play important roles in synthetic biology, sequencing, and diagnostic testing, but the experimental protocols involving bacteria are often complex and require numerous instruments. Digital microfluidics (DMF) offers a miniaturized platform to simplify the processes of bacterial protocols, from sample preparation to analysis. DMF devices can be used in conjunction with existing research tools or integrated into all-in-one packages, providing versatility and convenience. This perspective discusses the benefits, limitations, and potential future directions of DMF in bacterial studies.

SLAS TECHNOLOGY (2023)

Article Nanoscience & Nanotechnology

Antifouling Properties of Pluronic and Tetronic Surfactants in Digital Microfluidics

Man Ho, Aaron Au, Robert Flick, Thu V. Vuong, Alexandros A. Sklavounos, Ian Swyer, Christopher M. Yip, Aaron R. Wheeler

Summary: Fouling at liquid-solid interfaces is a severe problem for digital microfluidics (DMF) and can be combatted by including amphiphilic surfactant additives in the droplets. This study evaluated 19 different Pluronic and Tetronic additives to determine their antifouling performance, structural similarities, and mechanism of action. The analysis showed that Pluronic and Tetronic additives with specific characteristics can provide exceptional antifouling performance in DMF. The results and their implications are important progress for the DMF community and can guide the selection of surfactants for manipulating biological matrices.

ACS APPLIED MATERIALS & INTERFACES (2023)

Article Chemistry, Multidisciplinary

Steering Micromotors via Reprogrammable Optoelectronic Paths

Xi Chen, Xiaowen Chen, Mohamed Elsayed, Harrison Edwards, Jiayu Liu, Yixin Peng, H. P. Zhang, Shuailong Zhang, Wei Wang, Aaron R. Wheeler

Summary: Researchers have developed an optoelectronic strategy to control the motion of micromotors using programmable light patterns. By illuminating hydrogenated amorphous silicon, local electric field maxima are generated at the edge of the light pattern, attracting micromotors. This method allows for precise control of micromotors in customized paths and through complex microstructures, as well as enabling multiple motion modes and parallel control of multiple micromotors.

ACS NANO (2023)

Article Chemistry, Multidisciplinary

High-Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets

Kai-Hung Huang, Nicolas M. Morato, Yunfei Feng, R. Graham Cooks

Summary: Late-stage diversification of drug molecules is facilitated by reaction screening using high-throughput experimentation. In this study, a rapid method for functionalizing bioactive molecules based on accelerated reactions in microdroplets is presented. Using this method, an opioid agonist and an antagonist were diversified and characterized by tandem mass spectrometry after screening over 500 reactions.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2023)

Article Physics, Atomic, Molecular & Chemical

Automated desorption electrospray ionization two-dimensional tandem mass spectrometry: Instrumentation and software for high throughput analysis

Eric T. Dziekonski, Thomas C. Sams, Lucas J. Szalwinski, L. Edwin Gonzalez, R. Graham Cooks

Summary: Two-dimensional tandem mass spectrometry (2D-MS/MS) is employed to characterize each sample in an array by creating ion populations from complex mixtures using desorption electrospray ionization. Automated high-throughput examination of each sample in the array is achieved through integrated movement of the sample array and automated data acquisition. Position control is accomplished using an Arduino microprocessor, a RAMPS control board, two stepper motors, and a custom MATLAB graphical user interface. Data processing improvements are made to enhance visual discrimination of peaks from the background in local regions of the 2D spectrum.

INTERNATIONAL JOURNAL OF MASS SPECTROMETRY (2023)

Article Chemistry, Multidisciplinary

Re-Imagining Drug Discovery using Mass Spectrometry

R. Graham Cooks, Yunfei Feng, Kai-Hung Huang, Nicolas M. Morato, Lingqi Qiu

Summary: The article argues that mass spectrometry (MS) can be used sequentially for the three key steps in drug discovery: reaction screening, synthesis scale-up, and bioactivity assessment. The chosen ionization method, desorption electrospray ionization (DESI), is both an analytical technique and a procedure for small-scale synthesis. DESI is highly compatible with automation, allowing for high throughput in both synthesis and analysis.

ISRAEL JOURNAL OF CHEMISTRY (2023)

Article Biochemical Research Methods

Comparison of Database Searching Programs for the Analysis of Single-Cell Proteomics Data

Jiaxi Peng, Calvin Chan, Fei Meng, Yechen Hu, Lingfan Chen, Ge Lin, Shen Zhang, Aaron R. Wheeler

Summary: Single-cell proteomics is an important subfield with potential to reshape our understanding of cell development, differentiation, disease diagnosis, and therapy. This study compared seven popular proteomics programs on three different datasets, finding that MSGF+, MSFragger, and Proteome Discoverer are more efficient for maximizing protein identifications. MaxQuant is better for low-abundance proteins, MSFragger is superior in elucidating peptide modifications, and Mascot and X!Tandem are better for analyzing long peptides. The study also explored improvements in single-cell proteomics data analysis. Overall, this comparative study provides insight for both experts and beginners in single-cell proteomics.

JOURNAL OF PROTEOME RESEARCH (2023)

Review Chemistry, Analytical

Mass spectrometry in materials synthesis

Jyotirmoy Ghosh, R. Graham Cooks

Summary: Mass spectrometry (MS), a century-old analytical technique, is now being used as a preparative method. Electrospray deposition (ESD) of charged droplets generated by electrospray ionization (ESI) is an efficient way to form nanomaterials, including catalysts. By using mass-analyzed ions and performing ion soft landing (SL), higher chemical specificity in surface modification can be achieved, although this vacuum-based method is slow due to low ion currents. MS-based synthesis by ESD or SL provides advantages over traditional approaches, allowing control over material properties and surface patterning without the need for additives or reducing agents.

TRAC-TRENDS IN ANALYTICAL CHEMISTRY (2023)

Review Chemistry, Multidisciplinary

Desorption Electrospray Ionization Mass Spectrometry: 20 Years

Nicolas M. Morato, R. Graham Cooks

Summary: Mass spectrometry (MS) is widely used in the chemical sciences for various applications such as monitoring reaction products, identifying disease biomarkers, and measuring thermodynamic parameters. Electrospray ionization (ESI) is a commonly used method to ionize polar compounds from solution. Desorption electrospray ionization (DESI) is a technique that directly generates ions from objects in the ambient environment. The simplicity and wide applicability of DESI revolutionized the analysis of complex materials for their organic components, particularly for in situ applications.

ACCOUNTS OF CHEMICAL RESEARCH (2023)

Article Chemistry, Multidisciplinary

Quantitative Determination of Water in Organic Liquids by Ambient Mass Spectrometry

Lingqi Qiu, Mousumi Saha, Stefan Kraft, Eric T. Dziekonski, Christopher J. Welch, Yumin Dai, Andreas Kaerner, R. Graham Cooks

Summary: This study employs a rapid tandem mass-spectrometry method for determining water content in complex organic solutions, with a focus on trace-water analysis. Water is captured using a charge-labeled molecular probe, which selectively binds to the strongly electrophilic aldehyde site. This method allows for quantitative determinations over a wide concentration range with high accuracy and short analysis times.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2023)

Article Physics, Atomic, Molecular & Chemical

Enabling one- and two-dimensional mass spectrometry in a linear quadrupole ion trap

Eric T. Dziekonski, Gregory S. Eakins, R. Graham Cooks

Summary: In this study, an Arduino Uno microcontroller is used to control several electrical/electromechanical switches and the timing of all experimental subsystems in response to the instrument trigger output and a user selected operating mode. By calibrating and measuring the RF amplitude control signal in 1D mode, it is possible to calculate the applied RF amplitude in 2D mode, thereby allowing the user to determine relevant quadrupole operating parameters for a particular sample.

INTERNATIONAL JOURNAL OF MASS SPECTROMETRY (2023)

Article Biochemical Research Methods

Digital Microfluidics for Microproteomic Analysis of Minute Mammalian Tissue Samples Enabled by a Photocleavable Surfactant

Calvin Chan, Jiaxi Peng, Vigneshwar Rajesh, Erica Y. Scott, Alexandros A. Sklavounos, Maryam Faiz, Aaron R. Wheeler

Summary: The proteome profiles of small tissue samples have great clinical potential, but conventional proteomic methods are not suitable for analyzing these samples. Researchers have developed an automated digital microfluidic workflow using a photocleavable surfactant, which enables the efficient analysis of small tissue samples and identifies a large number of proteins.

JOURNAL OF PROTEOME RESEARCH (2023)

Article Chemistry, Analytical

Miniature mass spectrometer-based point-of-care assay for measuring phosphatidylethanol in blood

Sangeeta Pandey, Yanyang Hu, Peter L. Anderson, Jennifer J. Kiser, R. Graham Cooks

Summary: We validate the concept of point-of-care assessment of long-term alcohol consumption by measuring phosphatidylethanol in blood/dried blood spots using nano-electrospray ionization and MS/MS with a miniature mass spectrometer. The levels of "abstinence", "moderate", and "chronic" consumption can be rapidly distinguished for both sample types, and quantitative analysis is achieved with blood samples (LoQ-100 ng mL(-1)).

ANALYST (2023)

Article Biochemical Research Methods

Digital microfluidics with distance-based detection - a new approach for nucleic acid diagnostics

Man Ho, N. Sathishkumar, Alexandros A. Sklavounos, Jianxian Sun, Ivy Yang, Kevin P. Nichols, Aaron R. Wheeler

Summary: This study developed a new microfluidic system that combines digital microfluidics (DMF) with distance-based detection (DBD) for LAMP-based point-of-care nucleic acid amplification tests (POC NAATs). The system allows for direct signal readout without the need for dedicated optical detection apparatus. The method was validated for SARS-CoV-2 detection in saliva and showed promising results. The combination of DMF with DBD holds great potential for implementing various POC NAATs or other applications in the future.

LAB ON A CHIP (2023)

暂无数据