(ii) a trigger that controls autocatalytic growth; and (iii) inhibitory processes that remove activating thiol species produced during the autocatalytic cycle. In contrast to previous studies demonstrating oscillations and bistability using highly evolved biomolecules (i.e., enzymes 15 and DNA 16,17 ) or inorganic molecules of questionable biochemical relevance (e.g. those used in Belousov-Zhabotinsky-type reactions), 18,19 the organic molecules used in our network are relevant to current metabolism and similar to those that might have existed on early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable, and oscillatory behavior, we identified principles that clarify how dynamic networks relevant to life might possibly have developed. In the future, modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks, and of synthetic self-regulating and evolving chemical systems.3 Figure 1 summarizes the network of organic reactions that we used to assemble our model system. All of these reactions are nearly quantitative, and the structure of their reactants can be varied by synthesis to control rates of reactions. Thiols and thioesters, which are central to these reactions, are important in many biological processes (e.g., the formation of disulfide bonds in proteins, transformations involving coenzyme-A, the reduction of oxidized molecules by glutathione, 20 the synthesis of polyketides, 21 and the nonribosomal synthesis of peptides 21 ), and thus, might represent reactions that enabled life to emerge on early Earth. 22 To control the dynamics of these processes, we constructed a modular chemical reaction network (CRN) shown schematically in control-theoretic terms 23 in Fig. 1a. A "trigger" produces an initial chemical signal, and an "auto-amplifier" amplifies this signal, which may or may not be suppressed by inhibition. To keep the reactions out of equilibrium-and thus, to enable the self-organization of reactions by communication through concentrations of reactants and products -we used a continuous-stirred tank reactor (CSTR) to mix reactants and products, while allowing a flux of species into and out of the network over time. A biological cell has some conceptual analogies to a micron-scale, diffusively mixed, tank reactor. The dynamic behavior of this system -especially bistability and oscillationsreflects the balances of triggering, auto-amplification, and inhibition.We first constructed a chemical network capable of auto-amplification using thiols and thioesters (Fig. 1b). The starting components of the network are cystamine (CSSC, 3) and L-alanine ethyl thioester (AlaSEt, 2). Trace amounts of cysteamine (CSH, 1) are generated as follows: AlaSEt slowly hydrolyzes, generating alanine (8) and ethanethiol (ESH, 4); EtSH then reacts with CSSC via thiolate-disulfide interchange, 24 yielding disulfide 6 and CSH. With CSH present, self-amplification oc...

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Here, we present a platform to detect cytokine (IL-2, IFN-γ, TNF-α) secretion of single, activated T-cells in droplets over time. We use a novel droplet-based microfluidic approach to encapsulate cells in monodisperse agarose droplets together with functionalized cytokine-capture beads for subsequent binding and detection of secreted cytokines from single cells. This method allows high-throughput detection of cellular heterogeneity and maps subsets within cell populations with specific functions.

Charge transport through single molecules can be influenced by the charge and spin states of redox-active metal centres placed in the transport pathway. These molecular intrinsic properties are usually addressed by varying the molecule's electrochemical and magnetic environment, a procedure that requires complex setups with multiple terminals. Here we show that oxidation and reduction of organometallic compounds containing either Fe, Ru or Mo centres can solely be triggered by the electric field applied to a two-terminal molecular junction. Whereas all compounds exhibit bias-dependent hysteresis, the Mo-containing compound additionally shows an abrupt voltage-induced conductance switching, yielding high-to-low current ratios exceeding 1000 at voltage stimuli of less than 1.0 V. DFT calculations identify a localized, redox-active molecular orbital that is weakly coupled to the electrodes and closely aligned with the Fermi energy of the leads because of the spin-polarised ground state unique to the Mo centre. This situation opens an additional slow and incoherent hopping channel for transport, triggering a transient charging effect of the entire molecule and a strong hysteresis with unprecedented high low-to-high current ratios.

This paper describes rates of charge tunneling across self-assembled monolayers (SAMs) of compounds containing oligophenyl groups, supported on gold and silver, using Ga 2 O 3 /EGaIn as the top electrode. It compares the injection current, J 0 , and the attenuation constant, β, of the simplified Simmons equation, across oligophenyl groups (R = Ph n ; n = 1, 2, 3), with three different anchoring groups (thiol, HSR; methanethiol, HSCH 2 R; and acetylene, HC≡CR) that attach R to the template-stripped gold and silver substrates. The results demonstrate that the structure of the molecules between the anchoring group (-S-or -C≡C-) and the oligophenyl moiety significantly influences charge transport. SAMs of SPh n , and C≡CPh n on gold show similar values of β and log|J 0 | (β = 0.28 ± 0.03 Å -1 and log|J 0 | = 2.7 ± 0.1 for Au/SPh n ; β = 0.30 ± 0.02 Å -1 and log|J 0 | = 3.0 ± 0.1 for Au/C≡CPh n ). The introduction of a single intervening methylene (CH 2 ) group, between the anchoring sulfur atom and the aromatic units to generate SAMs of SCH 2 Ph n , increases β to ~0.6 Å -1 on both gold and silver substrates. (For nalkanethiolates on gold the corresponding values are β = 0.76 Å -1 and log|J 0 | = 4.2). As a generalization, based on this and other work, it seems that increasing the height of the tunneling barrier in the region of the interfaces increases β, and may decrease J 0 ; by contrast, it appears that lowering the height of the barrier at these interfaces has little influence on β or J 0 .