Analysis on the go: quantitation of drugs of abuse in dried urine with digital microfluidics and miniature mass spectrometry.

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 min 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.

Paper microfluidics goes digital.

The first example of so-called "digital microfluidics" (DMF) implemented on paper by inkjet printing is reported. A sandwich enzyme-linked immunosorbent assay (ELISA) is demonstrated as an example of a complex, multistep protocol that would be difficult to achieve with capillary-driven paper microfluidics. Furthermore, it is shown that paper-based DMF devices have comparable performance to traditional photolithographically patterned DMF devices at a fraction of the cost.

Digital microfluidics: an emerging sample preparation platform for mass spectrometry.

Mass spectrometry (MS) has become an indispensable tool for laboratory science, but a drawback is the laborious sample processing required before MS analysis. Digital microfluidics (DMF), a microscale liquid handling technique characterized by the manipulation of fluid droplets on open electrode arrays, presents a potential solution to this problem. In DMF, discrete droplets can be made to merge, mix, split, and dispense from reservoirs. Since droplets are manipulated individually and act as discrete microreactors, DMF is well suited for microscale sample processing. Coupling the versatility of MS analysis with DMF sample handling has been beneficial for a number of DMF-based applications, including proteomics, chemical synthesis, and clinical diagnostics. In this review, we provide a summary of efforts to integrate these two technologies, focusing on examples of both off-line and in-line MS analysis for DMF sample processing.

Microfluidic origami: a new device format for in-line reaction monitoring by nanoelectrospray ionization mass spectrometry.

Microfluidics is an attractive platform for chemical synthesis because it offers fast reaction times, reduced reagent usage, and the ability to integrate multiple functions on a single device. Digital Microfluidics (DMF) is particularly well-suited for microscale chemical synthesis, as it permits discretized sample handling, allowing for total process control. However, a limitation of DMF-based synthesis is analysis, which is often performed offline. To this end, we have developed "microfluidic origami", a new device format that integrates DMF with in-line analysis by mass spectrometry (MS). This format comprises a DMF platform and a folded nanoelectrospray ionization (nanoESI) emitter formed on a single flexible polyimide film substrate. Additionally, the device contains a two-plate-to-one-plate DMF interface, which allows for straightforward coupling of micro-reaction operations and product delivery to the emitter for analysis. The integrated platform was used to perform the Morita-Baylis-Hillman (MBH) reaction using DMF followed by inline MS analysis for monitoring the reaction progress in real-time. We propose that this platform has potential as a new tool for real-time monitoring of reaction rates and reaction pathways and could be a useful addition to the synthetic organic chemistry laboratory.

Folded emitters for nanoelectrospray ionization mass spectrometry.

Electrospray ionization (ESI) has revolutionized mass spectrometry (MS), providing a facile method for the ionization of macromolecules for analysis by mass. The development of nanoESI-MS has further extended the utility of ESI-MS, permitting the analysis of small-volume samples with enhanced sensitivity over conventional ESI-MS. Traditional nanoESI-MS experiments use pulled-glass capillary emitters, which are expensive to purchase and require specialized instruments and training to fabricate in-house. Furthermore, these emitters suffer from problems including clogging, sample contamination, and irreproducible spray stability. Here, we report a new emitter for nanoESI-MS, made by folding small pieces of polyimide tape. In comparison with conventional pulled-glass capillary emitters, the new emitters are inexpensive and simple to make. Their low cost makes them disposable after a single use, such that sample contamination or clogging is never a problem. Emitter performance has been evaluated for diverse analytes encompassing a large mass range, including small molecules, peptides, proteins, and synthetic polymers. In all cases, the performance is similar to that of pulled-glass capillary emitters, with the advantages of low cost, ease of use, and disposability.

Silane-controlled diastereoselectivity in the tris(pentafluorophenyl)borane-catalyzed reduction of alpha-diketones to silyl-protected 1,2-Diols.

B(C(6)F(5))(3)-catalyzed bis(hydrosilylation) of alpha-diketones can give high diastereomeric excess of either meso/anti (small silanes and disilane reagents) or dl/syn (bulky silanes) silyl-protected 1,2-diols. This easily tuned diastereoselectivity is rationalized based on the classic Felkin-Anh model applied to a mechanism relying on Si-H abstraction by the electrophilic borane reagent.