@article{taniguchi_hu_liu_du_lindsey_2018, title={Red and near-infrared fluorophores inspired by chlorophylls. Consideration of practical brightness in multicolor flow cytometry and biomedical sciences}, volume={10508}, ISSN={["1996-756X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85047458937&partnerID=MN8TOARS}, DOI={10.1117/12.2302709}, abstractNote={Demands in flow cytometry for increased multiplexing (for detection of multiple antigens) and brightness (for detection of rare entities) require new fluorophores (i.e., “colors”) with spectrally distinct fluorescence outside the relatively congested visible spectral region. Flow cytometry fluorophores typically must function in aqueous solution upon bioconjugation and ideally should exhibit a host of photophysical features: (i) strong absorption, (ii) sizable Stokes shift, (iii) modest if not strong fluorescence, and (iv) narrow fluorescence band. Tandem dyes have long been pursued to achieve a large effective Stokes shift, increased brightness, and better control over the excitation and emission wavelengths. Here, the attractive photophysical features of chlorophylls and bacteriochlorophylls – Nature’s chosen photoactive pigments for photosynthesis – are described with regards to use in flow cytometry. A chlorophyll (or bacteriochlorophyll) constitutes an intrinsic tandem dye given the red (or near-infrared) fluorescence upon excitation in the higher energy ultraviolet (UV) or visible absorption bands (due to rapid internal conversion to the lowest energy state). Synthetic (bacterio)chlorins are available with strong absorption (near-UV molar absorption coefficient ε(λexc) ~105 M-1cm-1), modest fluorescence quantum yield (Φf = 0.05–0.30), and narrow fluorescence band (10–25 nm) tunable from 600–900 nm depending on synthetic design. The “relative practical brightness” is given by intrinsic brightness [ε(λexc) x Φf] times ηf, the fraction of the fluorescence band that is captured by an emission filter in a multicolor experiment. The spectroscopic features of (bacterio)chlorins are evaluated quantitatively to illustrate practical brightness for this novel class of fluorophores in a prospective 8-color panel.}, journal={REPORTERS, MARKERS, DYES, NANOPARTICLES, AND MOLECULAR PROBES FOR BIOMEDICAL APPLICATIONS X}, publisher={SPIE}, author={Taniguchi, Masahiko and Hu, Gongfang and Liu, Rui and Du, Hai and Lindsey, Jonathan S.}, editor={Achilefu, Samuel and Raghavachari, RameshEditors}, year={2018} }
 @article{taniguchi_du_lindsey_2013, title={Enumeration of Virtual Libraries of Combinatorial Modular Macrocyclic (Bracelet, Necklace) Architectures and Their Linear Counterparts}, volume={53}, ISSN={["1549-960X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84883274376&partnerID=MN8TOARS}, DOI={10.1021/ci400175f}, abstractNote={A wide variety of cyclic molecular architectures are built of modular subunits and can be formed combinatorially. The mathematics for enumeration of such objects is well-developed yet lacks key features of importance in chemistry, such as specifying (i) the structures of individual members among a set of isomers, (ii) the distribution (i.e., relative amounts) of products, and (iii) the effect of nonequal ratios of reacting monomers on the product distribution. Here, a software program (Cyclaplex) has been developed to determine the number, identity (including isomers), and relative amounts of linear and cyclic architectures from a given number and ratio of reacting monomers. The program includes both mathematical formulas and generative algorithms for enumeration; the latter go beyond the former to provide desired molecular-relevant information and data-mining features. The program is equipped to enumerate four types of architectures: (i) linear architectures with directionality (macroscopic equivalent = electrical extension cords), (ii) linear architectures without directionality (batons), (iii) cyclic architectures with directionality (necklaces), and (iv) cyclic architectures without directionality (bracelets). The program can be applied to cyclic peptides, cycloveratrylenes, cyclens, calixarenes, cyclodextrins, crown ethers, cucurbiturils, annulenes, expanded meso-substituted porphyrin(ogen)s, and diverse supramolecular (e.g., protein) assemblies. The size of accessible architectures encompasses up to 12 modular subunits derived from 12 reacting monomers or larger architectures (e.g. 13-17 subunits) from fewer types of monomers (e.g. 2-4). A particular application concerns understanding the possible heterogeneity of (natural or biohybrid) photosynthetic light-harvesting oligomers (cyclic, linear) formed from distinct peptide subunits.}, number={9}, journal={JOURNAL OF CHEMICAL INFORMATION AND MODELING}, publisher={American Chemical Society (ACS)}, author={Taniguchi, Masahiko and Du, Hai and Lindsey, Jonathan S.}, year={2013}, month={Sep}, pages={2203–2216} }
 @article{taniguchi_du_lindsey_2011, title={Virtual Libraries of Tetrapyrrole Macrocycles. Combinatorics, Isomers, Product Distributions, and Data Mining}, volume={51}, ISSN={["1549-960X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80053326969&partnerID=MN8TOARS}, DOI={10.1021/ci200240e}, abstractNote={A software program (PorphyrinViLiGe) has been developed to enumerate the type and relative amounts of substituted tetrapyrrole macrocycles in a virtual library formed by one of four different classes of reactions. The classes include (1) 4-fold reaction of n disubstituted heterocycles (e.g., pyrroles or diiminoisoindolines) to form β-substituted porphyrins, β-substituted tetraazaporphyrins, or α- or β-substituted phthalocyanines; (2) combination of m aminoketones and n diones to form m × n pyrroles, which upon 4-fold reaction give β-substituted porphyrins; (3) derivatization of an 8-point tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and pyrrole to form meso-substituted porphyrins. The program accommodates variable ratios of reactants, reversible or irreversible reaction (reaction classes 1 and 2), and degenerate modes of formation. Pólya's theorem (for enumeration of cyclic entities) has also been implemented and provides validation for reaction classes 3 and 4. The output includes the number and identity of distinct reaction-accessible substituent combinations, the number and identity of isomers thereof, and the theoretical mass spectrum. Provisions for data mining enable assessment of the number of products having a chosen pattern of substituents. Examples include derivatization of an octa-substituted phthalocyanine with eight reagents to afford a library of 2,099,728 members (yet only 6435 distinct substituent combinations) and reversible reaction of six distinct disubstituted pyrroles to afford 2649 members (yet only 126 distinct substituent combinations). In general, libraries of substituted tetrapyrrole macrocycles occupy a synthetically accessible region of chemical space that is rich in isomers (>99% or 95% for the two examples, respectively).}, number={9}, journal={JOURNAL OF CHEMICAL INFORMATION AND MODELING}, publisher={American Chemical Society (ACS)}, author={Taniguchi, Masahiko and Du, Hai and Lindsey, Jonathan S.}, year={2011}, month={Sep}, pages={2233–2247} }
 @article{matsumoto_du_lindsey_2002, title={A parallel simplex search method for use with an automated chemistry workstation}, volume={62}, ISSN={["0169-7439"]}, DOI={10.1016/S0169-7439(02)00010-2}, abstractNote={The Simplex method, an inherently serial means of optimization, can be used to search for improved conditions for chemical reactions. We have developed an automated chemistry workstation equipped for parallel adaptive experimentation. To exploit the capabilities of the workstation and thereby optimize reaction conditions in a more expedient manner, we have developed an experiment-planning module for performing Simplex searches in parallel. The parallel Simplex search (PSS) module enables multiple composite modified Simplex (CMS) searches to be performed in a concurrent manner. Features have been incorporated for two applications. (1) Multiple concurrent simplex searches in one search space, enabling optimization of conditions for one reaction. The use of Simplex searches starting from several points in a search space reduces the possibility of falsely concluding that a local maximum is the global maximum. (2) Concurrent investigation of multiple search spaces with one Simplex search per space, enabling optimization of conditions for each member of a set of catalysts or set of reactants for a given reaction. This latter feature is useful for combinatorial chemistry applications. All individual Simplex searches in a PSS study must employ the same experimental template. The PSS module includes options to define conditions for simplex moves as well as specifying initial points in the search space. Provisions are included for stop criteria, termination of an individual Simplex search, and global termination of multiple Simplex searches. The PSS method provides a parallel yet adaptive means for identifying improved conditions for chemical reactions.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Matsumoto, T and Du, H and Lindsey, JS}, year={2002}, month={May}, pages={129–147} }
 @article{matsumoto_du_lindsey_2002, title={A two-tiered strategy for simplex and multidirectional optimization of reactions with an automated chemistry workstation}, volume={62}, ISSN={["0169-7439"]}, DOI={10.1016/S0169-7439(02)00011-4}, abstractNote={A two-tiered strategy for optimizing reaction conditions has been developed for use with an automated chemistry workstation capable of parallel adaptive experimentation. In tier one, a broad survey of conditions is performed in parallel. In tier two, the promising region identified in the first tier is used as the starting point for in-depth searches. The search strategies employed in tier two include the composite-modified Simplex (CMS), multidirectional search (MDS), and parallel Simplex search (PSS) methods. Accordingly, this two-tiered strategy has been integrated into the CMS, MDS, and PSS experiment-planning modules. Each of these methods requires an initial user-defined simplex to explore reaction conditions. The breadth-first survey avoids the lengthy experimentation that occurs when the initial simplex is located far from the optimal region, and also diminishes the possibility of trapping in local maxima. Thus, the two-tiered strategy (breadth-first, depth-second) enables the optimal region to be reached rapidly.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Matsumoto, T and Du, H and Lindsey, JS}, year={2002}, month={May}, pages={149–158} }
 @article{du_lindsey_2002, title={An approach for parallel and adaptive screening of discrete compounds followed by reaction optimization using an automated chemistry workstation}, volume={62}, ISSN={["0169-7439"]}, DOI={10.1016/S0169-7439(02)00012-6}, abstractNote={The challenge of finding appropriate reagents, catalysts, or cocatalysts for chemical reactions is typically met with a strategy of surveying broadly to identify a good starting point (i.e., a hit) from which an in-depth optimization can be performed. We have developed an approach for experiment planning that enables this two-tiered strategy to be implemented on an automated chemistry workstation. One experiment-planning module (Parascreen) for screening discrete substances to identify hits is linked to a second module (Multidirectional search, MDS) for optimization of each hit compound. The screening module has been constructed through modification of an experiment-planning module for performing grid searches. Each candidate is examined over a range of concentrations. Two levels of decision-making are performed. (1) Local evaluation: Yield-versus-time data from a given reaction are examined in a pattern-matching procedure to assess whether monitoring should be continued or terminated. (2) Global evaluation: When a user-defined threshold (e.g., yield) is reached, the candidate is flagged as a hit; any experiments at higher concentration of the same candidate are deleted. Each of the hit compounds is subjected to identification of refined conditions by means of an MDS optimization. Each module alone enables parallel adaptive experimentation. Several issues for automated use of two different modules in succession have been addressed. This two-tiered approach of breadth-first screening followed by in-depth optimization of hits enables autonomous experimentation using an automated chemistry workstation.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Du, H and Lindsey, JS}, year={2002}, month={May}, pages={159–170} }
 @article{dixon_du_cork_lindsey_2002, title={An experiment planner for performing successive focused grid searches with an automated chemistry workstation}, volume={62}, ISSN={["1873-3239"]}, DOI={10.1016/S0169-7439(02)00009-6}, abstractNote={Automated chemistry workstations equipped for parallel and adaptive experimentation can provide a significant impact in chemistry research, particularly for exploring search spaces as part of optimization studies. A traditional method of investigating a search space involves generation of a response surface upon examination of a regular grid of points (e.g., as in a full factorial design). Such experimental approaches are compatible with parallel experimentation but are not adaptive in directing the search toward favorable regions of the search space. We have developed an algorithm wherein a succession of grid searches is performed in a search space. The location of the optimal response obtained in one search cycle constitutes the location about which a subsequent more fine-grained search is performed. In this manner, a sequential iterative optimization can be achieved: one cycle is comprised of a set of parallel reactions followed by data evaluation, and multiple cycles occur until one of several user-defined termination criteria is satisfied. In successive cycles, the number of levels on each dimension can be decremented and the range of each dimension can be decreased by a defined “shrinkage” factor. The resulting successive focused grid search (SFGS) affords a breadth-first then in-depth study. We have developed an experimental planner that enables the SFGS algorithm to be implemented on an automated chemistry workstation. Options are available for adjusting the scope of experimentation to conserve material resources (e.g., solvent, reagents, reactants) or to curtail the duration of experimentation. Collectively, the SFGS module enables parallel adaptive experimentation and affords a comprehensive response surface that is fine-grained in the region of optimal response.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Dixon, JM and Du, H and Cork, DG and Lindsey, JS}, year={2002}, month={May}, pages={115–128} }
 @article{kuo_du_corkan_yang_lindsey_1999, title={A planning module for performing grid search, factorial design, and related combinatorial studies on an automated chemistry workstation}, volume={48}, ISSN={["0169-7439"]}, DOI={10.1016/S0169-7439(99)00021-0}, abstractNote={The investigation of combinations of factors in a defined search space has broad application in chemistry experimentation. The factors can involve continuous variables such as concentration and temperature, or discrete variables such as chemical reactants or reagents. The number of data points rapidly becomes quite large in such factorial experimentation, which can be adequately handled through the use of an automated chemistry workstation. The automated chemistry workstation utilizes experiment templates for implementation of factorial designs. Experimental templates represent generic plans that are used repetitively with slight variation of designated parameters for the chemical system under investigation. A linkage is established between the dimensions of the search space and the variables in the experimental template. Various patterns of points can be selected, enabling the composition of full factorial or partial factorial designs. The search space points are inscribed in the experimental template, giving rise to one experimental plan per point in the search space. The experimental plans are assessed for resource availability and those for which resources are sufficient are then scheduled for parallel implementation on a microscale automated chemistry workstation. An adaptive feature allows unproductive experiments to be terminated early, de-allocating resources for use in other experiments. Experimental plans can be readily composed and implemented for fundamental studies of chemical reactions, generating response surfaces, performing parallel screening procedures, and creating indexed combinatorial chemical libraries.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Kuo, PY and Du, H and Corkan, LA and Yang, KX and Lindsey, JS}, year={1999}, month={Aug}, pages={219–234} }
 @article{du_corkan_yang_kuo_lindsey_1999, title={An automated microscale chemistry workstation capable of parallel, adaptive experimentation}, volume={48}, ISSN={["0169-7439"]}, DOI={10.1016/S0169-7439(99)00019-2}, abstractNote={We have designed and constructed a 3rd-generation chemistry workstation and accompanying software for automated experimentation in relatively clean domains of chemistry. The workstation is designed for flexible, high-throughput, microscale chemistry and includes a reaction station with 60 reaction vessels. The experiment manager software includes a large number of features to facilitate experiment planning and implementation. The significant advances in software from the 2nd-generation system include the following: (1) Five experiment-planning modules have been incorporated to match different types of scientific experimentation, including open-loop and closed-loop experiments. The five modules enable plans to be composed for general-purpose (GP), decision-tree (DT), factorial design (FD), composite modified Simplex (CMS) and multidirectional search (MDS) experiments. (2) Parallel experimentation and adaptive experimentation have been blended so that some decision-making can be done using objective functions or early-termination functions while multiple experiments are in progress. Some planning modules (CMS, MDS and DT) can cause new experiments to be spawned based on the chemistry data obtained. (3) Decision-making can involve the local course of individual experiments and/or the global course of sets of experiments. (4) Resource management features provide the capability to look-ahead at experiments in queue, assess resource (chemicals, containers) availability and designate suitability for implementation. (5) Intelligent reagent-handling features support the autodilution of reagents, autoselection of appropriate stock solutions, autoassignment of containers and control over reaction volumes. (6) Opportunistic rescheduling features have been provided so that pending experiments can be advanced in queue whenever possible, leading to compressed experimental timeframes. (7) Templates composed for FD, CMS and MDS experiments can be stored and reused with modifications as required for specific experiments. (8) The scheduling module contains both a rigid scheduler and a flexible scheduler. (9) The software is modular and runs under Windows 95. This workstation is especially designed for fundamental investigations of chemical reactions and optimization of experimental reaction conditions.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Du, H and Corkan, LA and Yang, KX and Kuo, PY and Lindsey, JS}, year={1999}, month={Aug}, pages={181–203} }
 @article{cork_sugawara_lindsey_corkan_du_1999, title={Further development of a versatile microscale automated workstation for parallel adaptive experimentation}, volume={11}, DOI={10.1002/(SICI)1098-2728(1999)11:4<217::AID-LRA6>3.3.CO;2-3}, abstractNote={We have further developed our microscale automated chemistry workstation for investigating the optimization of reaction conditions. The workstation includes a Cartesian robot for solvent delivery and reagent/sample handling, a 60-vessel reaction block, a UV–Vis absorption spectrometer, and vial racks for compound storage. This article describes the following hardware additions that increase the scope and versatility of the workstation: (a) an analytical high performance liquid chromatography (HPLC) instrument and accompanying hardware interface (slide rail, autosampler); (b) three reactor blocks of 20 vessels each, with independent temperature control of each reactor block between ca. 0 and 80°C; (c) a shaker rack for mixing, dilution, or extraction of samples; (d) a rotary valve on the dispense line for complete isolation of 4 independent solvent lines; (e) sample workup features using disposable cartridges or filters; (f) provisions for dispensing inert gas, for example, for flushing through reactors or for storing solvents and performing transfer/dispense operations under. Using the new features, we are able to obtain useful analytical data from a wider range of reaction mixtures, perform parallel reactions at different temperatures, and handle solvents and sensitive reagents. © 1999 John Wiley & Sons, Inc. Lab Robotics and Automation 11: 217–223, 1999}, number={4}, journal={Laboratory Robotics and Automation}, author={Cork, D. G. and Sugawara, T. and Lindsey, Jonathan and Corkan, L. A. and Du, H.}, year={1999}, pages={217–223} }
 @article{du_jindal_lindsey_1999, title={Implementation of the multidirectional search algorithm on an automated chemistry workstation. A parallel yet adaptive approach for reaction optimization}, volume={48}, ISSN={["0169-7439"]}, DOI={10.1016/S0169-7439(99)00022-2}, abstractNote={We have developed an experiment-planning module for applying a powerful new pattern search algorithm toward the problems of reaction investigation and optimization. The experiment planner works in conjunction with a closed-loop automated chemistry workstation equipped for parallel experimentation. The new algorithm, developed by Torczon for parallel computation of mathematical functions, achieves a focused yet parallel approach to finding regions of improved response. Like a full factorial design, the search space involves a regular grid of points. Like the Simplex algorithm, the multidirectional search (MDS) algorithm uses the movement of a simplex through a search space. However, with each movement all points except the single best are discarded, whereas the Simplex algorithm discards only the one worst point. Thus, in an n-dimensional space, the MDS algorithm projects n mandatory points at every cycle (beyond the initial). In addition, a larger number of exploratory points are identified by look-ahead projection of possible future simplices. Such exploratory points lie on multiple independent lines of search. The responses for the mandatory and exploratory points are acquired via parallel experimentation, with the latter points examined to the extent that the workstation has available capacity during the same schedule. The data from such exploratory points can be used in later cycles of experimentation, accelerating convergence on the region of optimal response. In the case of unlimited parallel experimentation capacity, all possible points in the space are projected, as in a full factorial design. The MDS algorithm thus adapts to the available parallel capacity of the workstation. The MDS planning module includes options for specifying initial points, stop criteria, and early-termination processes. Provisions are included for parallel scheduling of batches of experiments, convergence of the search, and movement at the boundaries of the search space. An MDS investigation can thus be implemented with global decision-making concerning movements through a search space, and local decision-making concerning termination of individual experiments. The MDS algorithm enables directed evolutionary searches in a parallel mode and is ideally suited for rapid optimization of chemical reactions using a microscale automated chemistry workstation.}, number={2}, journal={CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS}, author={Du, H and Jindal, S and Lindsey, JS}, year={1999}, month={Aug}, pages={235–256} }
 @article{wagner_li_du_lindsey_1999, title={Investigation of cocatalysis conditions using an automated microscale multireactor workstation: Synthesis of meso-tetramesitylporphypin}, volume={3}, ISSN={["1083-6160"]}, DOI={10.1021/op9800459}, abstractNote={Prior manual work has shown that the condensation of mesitaldehyde and pyrrole leading to tetramesitylporphyrin depends sensitively on concentration and requires cocatalysis involving BF3·O(Et)2 and ethanol or other protic species. We have applied an automated microscale chemistry workstation capable of parallel or adaptive experimentation to systematically investigate these cocatalysis conditions. Examination of experimental grids spanning a 1000-fold range of the concentrations of BF3·O(Et)2 and ethanol identified the best cocatalysis conditions for various mesitaldehyde and pyrrole concentrations. As the reaction concentration increased from 10 to 200 mM, the optimal yields were achieved with a parallel increase in BF3·O(Et)2 concentration (from 3.3 to 56 mM), but the amount of ethanol remained relatively constant. Catalysis conditions were identified that afforded ∼30% yields for reactants in the range of 10−73 mM, thereby enabling the reaction to be performed at increased concentration without loss i...}, number={1}, journal={ORGANIC PROCESS RESEARCH & DEVELOPMENT}, author={Wagner, RW and Li, FR and Du, H and Lindsey, JS}, year={1999}, pages={28–37} }
 @article{du_fuh_li_corkan_lindsey_1998, title={PhotochemCAD: A computer-aided design and research tool in photochemistry}, volume={68}, DOI={10.1562/0031-8655(1998)068<0141:PACADA>2.3.CO;2}, number={2}, journal={Photochemistry and Photobiology}, author={Du, H. and Fuh, R. C. A. and Li, J. Z. and Corkan, L. A. and Lindsey, Jonathan}, year={1998}, pages={141–142} }