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towards the mother droplet and merge with it. The mother droplet grows proportionally, blocking the flow of the immiscible, or ‘oil’, phase. This causes a build-up in pressure and the mother droplet ejects a diluted daughter droplet at the outlet. The mother droplet then shrinks, allowing the oil phase to resume flow. The process repeats with the next diluent droplet. All the while, the mother droplet rotates, constantly mixing its contents, because of the surface drag generated by the flow of the oil phase past the mother droplet.

The idea of using a trapped mother droplet is compelling for two reasons. First, it simplifies device design and obviates the need for external equipment or active elements on chip. Device complexity is the ‘elephant in the room’ of the lab-on-a-chip field. Even though a chip may use liquid volumes in the subnanolitre range, more often than not a significant amount of tubing, syringes, pumps and power supplies

are required for operation. Second, using a trapped mother droplet allows both the number of droplets and dilution step size to be controlled, which in turn makes it attractive for a wide number of applications. The droplet parameters are controlled by simply adjusting the diluent flow rate and droplet size, respectively. The mother droplet does all the work, rather than external pumps or tubing. No pipettes are required, either.

As a demonstration of their device, deMello and co-workers peformed a DNA-binding assay. The advantage conferred by the sequential dilution is that it allowed them to probe an extreme range of concentrations and to do so with only nanolitres of reagent. It is true to say that this assay could have been done by hand in a lab. This point, however, misses the bigger picture: the process was done automatically within a microfluidic chip, which opens up the possibility of performing more ambitious screens that include more dilutions. Imagine replacing a factory floor

full of robots and countless multiwell plates with a few dozen chips connected to as many syringe pumps, and you will have an idea of why this is so exciting. ❐

Glenn M. Walker is in the Biomedical Engineering Department at North Carolina State University, Raleigh, North Carolina 27695, USA. e-mail: gmwalker@ncsu.edu

References1. Niu, X., Gielen, F., Edel, J. B. & deMello, A. J. Nature Chem.

3, 437–442 (2011).2. Mao, H. B., Yang, T. L. & Cremer, P. S. Anal. Chem.

74, 379–385 (2002).3. Jacobson, S. C., McKnight, T. E. & Ramsey, J. M. Anal. Chem.

71, 4455–4459 (1999).4. Jiang, X., Ng, J. M. K., Stroock, A. D., Dertinger, S. K. W. &

Whitesides, G. M. J. Am. Chem. Soc. 125, 5294–5295 (2003).5. Hansen, C. L., Skordalakes, E., Berger, J. M. & Quake, S. R.

Proc. Natl Acad. Sci. USA 99, 16531–16536 (2002).6. Tan, Y. C., Fisher, J. S., Lee, A. I., Cristini, V. & Lee, A. P. Lab Chip

4, 292–298 (2004).7. Song, H. & Ismagilov, R. J. Am. Chem. Soc.

125, 14613–14619 (2003).

Nanoporous crystalline materials such as zeolites and metal–organic frameworks pack vast available

surfaces into tiny volumes; they typically display surface areas of hundreds of square metres per gram of material. The ordered nanopores in these materials have molecular dimensions, which means that the adsorption energy and diffusion rates of guest molecules can vary greatly between species. These attributes make nanoporous crystals extremely valuable in industrial-scale chemical separations and catalysis applications, and extensive efforts have also been made to use them to develop high-performance membranes. However, the rate at which molecules can enter and exit and diffuse within the pores places strong limits on their possible performances in all of these applications. Investigating molecular transport in a specific material, Jörg Kärger and co-workers now reveal, in Journal of the American Chemical Society, the unexpected roles of blockage at its surface and defects within its pores1.

The most straightforward description of molecular diffusion in a nanoporous

crystal is illustrated in Fig. 1a for a material with one-dimensional channels. Inside a defect-free crystal, guest molecules diffuse along the periodic pores. The external boundaries of the crystal, in this description, are simple terminations of the pores that allow molecules to readily enter or exit. If this idealized description was accurate, molecular transport in the material would be controlled by the diffusion rate of the molecules inside the nanopores.

In recent experiments, Kärger and co-workers have tested this simplistic description using large single crystals of Zn(tbip) — a stable metal–organic framework composed of zinc metal centres bridged together by t-butyl-isophthalate ligands (tbip). The crystal structure of Zn(tbip) shows one-dimensional channels that are less than 0.5 nm wide2, so the illustration in Fig. 1a where a guest molecule fills most of the width of the pore is reasonable. Using carefully calibrated microscopy techniques3, Kärger and colleagues measured the concentration of various gases (propane, ethane, n-butane) adsorbed into selected crystals

as a function of time. The results are qualitatively inconsistent with the simple picture depicted in Fig. 1a, and can only be understood by taking into account some additional resistance to molecular diffusion — called surface barriers — at the entrances to each nanopore.

This is not the first inference that a surface barrier exists for nanoporous crystals4. The general concept that had emerged from earlier observations is that molecules considerably slow down as they enter or exit pores, as illustrated in Fig. 1b. The physical origin of this barrier is rarely specified but may arise, for example, from partial disorder in surface layers. This scenario however is not the only one to be consistent with the concentration profiles observed in Zn(tbip). Kärger and co-workers now suggest an alternative behaviour, shown in Fig. 1c, where some of the pore openings are completely blocked, yet the molecules that are inside the porous domain can move between adjacent channels through defects within the material. Readers who suffer through long commutes to work might think of this situation as analogous to traffic entering a multi-lane

METAL–ORGANIC FRAMEWORKS

A porous mazeObserving the diffusion of guest molecules in large single crystals of a metal–organic framework reveals surprising insights into the blockage of the channels at the material’s surface and the role of defects within its bulk.

David S. Sholl

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tunnel while the entrances to some lanes are closed by road works.

The study by Kärger and co-workers not only considers the two scenarios (Fig. 1b,c) as possible origins of a surface barrier, but also for the first time distinguishes which scenario applies to a specific material, Zn(tbip). Counter-intuitively, the scenario emerging from their analysis is the one in which some pores are completely blocked (Fig. 1c). The physical origin of these blockages is currently unknown, but the experiments give unambiguous evidence that pore entrances are blocked. Moreover, a statistical model developed further in another recent paper5 led to the estimation that only about one pore out of 2,000 on the surface of the crystals is open. This extremely low number implies that it is appropriate to think of the surface as an impermeable layer, pierced only on rare occasions by a pore giving access to the internal porosity.

Interpreting the experimental data in light of the model mentioned above clearly shows that molecules can ultimately access all of the porous domain. If most of the surface is blocked, this implies that defects are necessary to connect the channels. The same model that quantifies the external pore blockage also gives an estimate for the density of these defects. This description implies that, along any given pore, a defect appears every 8-16 nm that is large enough to allow molecules similar in size to the pore diameter to move into an adjacent channel. Thus, even though the material appears crystalline when examined with X-ray diffraction, it has a high density of internal defects that are large on molecular scales. The picture of metal–organic frameworks as perfect, crystalline structures is alluring, but

these experiments are a reminder that reality is more complex.

These findings raise a host of interesting questions. For the specific crystals of Zn(tbip) studied, can the origin of the surface blockage be identified, controlled or removed? Can the defects that allow molecules to move between pores be understood in terms of the chemical network that forms the crystal? More generally, Zn(tbip) is just one material among the thousands of nanoporous crystals

that have been synthesized. Is the existence of significant surface blockages and large numbers of internal structural defects a common situation, or is Zn(tbip) unusual? Developing a deeper understanding of internal defects that affect diffusion could significantly influence applications where differences in diffusion rates are exploited to achieve chemical separations6.

The existence of surface barriers to molecular motions is not necessarily a bad thing. In the protein channels that transport potassium ions through cell membranes, for example, discrimination between different ions takes place in a ‘selectivity filter’ at the pore entrance, and ion transport within pore is rapid7. This situation can be thought of as an extreme example of a surface resistance. Efforts have been made to create surface barriers on zeolites to enhance the separation abilities of zeolite membranes8. Future work along the lines of the study by Kärger and co-workers may ultimately enable us to control traffic through nanopores, rather than simply identify road signs that tell us when lanes are closed. ❐

David S. Sholl is in the School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA. e-mail: david.sholl@chbe.gatech.edu

References1. Hibbe, F. et al. J. Am. Chem. Soc. doi:10.1021/ja108625z (2011).2. Pan, L. et al. J. Am. Chem. Soc. 128, 4180–4181 (2006).3. Heinke, L. et al. Phys. Rev. Lett. 102, 065901 (2009).4. Micke, A., Bulow, M. & Kocirik, M. J. Phys. Chem.

98, 924–929 (1994).5. Heinke, L. & Kärger, J. Phys. Rev. Lett. 106, 074501(2011).6. Haldoupis, E., Nair, S. & Sholl, D. S. J. Am. Chem. Soc.

132, 7528–7539 (2010).7. Doyle, D. A. et al. Science 280, 69–77 (1998).8. Hong, M., Falconer, J. L. & Noble, R. D. Ind. Eng. Chem. Res.

44, 4035–4041 (2005).

Figure 1 | Illustration of three possible scenarios for molecules diffusing through a crystal with parallel one-dimensional pores. a, A defect-free crystal with no barriers to entering and exiting the pores. b, A defect-free crystal where the molecules entering and exiting the pores are slowed down by a surface barrier. c, A crystal in which many pore entrances are blocked, and molecules — once inside the bulk — can move between adjacent channels through defects in the crystal.

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© 2011 Macmillan Publishers Limited. All rights reserved