Wu A, Zhang Q, Lambert Khin Gatenby RA Kim HJ Pourmand Bussey Davies PC Sturm JC Austin RH. GZN. “Ancient hot and cold genes and chemotherapy resistance emergence.Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10467-72. doi: 10.1073/pnas.1512396112. Epub 2015 Aug 3. (2015). Publisher's VersionAbstract

We use a microfabricated ecology with a doxorubicin gradient and population fragmentation to produce a strong Darwinian selective pressure that drives forward the rapid emergence of doxorubicin resistance in multiple myeloma (MM) cancer cells. RNA sequencing of the resistant cells was used to examine (i) emergence of genes with high de novo substitution densities (i.e., hot genes) and (ii) genes never substituted (i.e., cold genes). The set of cold genes, which were 21% of the genes sequenced, were further winnowed down by examining excess expression levels. Both the most highly substituted genes and the most highly expressed never-substituted genes were biased in age toward the most ancient of genes. This would support the model that cancer represents a revision back to ancient forms of life adapted to high fitness under extreme stress, and suggests that these ancient genes may be targets for cancer therapy.

Chen Y, Abrams ES, Boles TC Pedersen JN Flyvbjerg Austin RH Sturm JC. H. “Emergence of antibiotic resistance from multinucleated bacterial filaments.Phys Rev Lett. 2015 May 15;114(19):198303. Epub 2015 May 15. (2015). Publisher's VersionAbstract

We demonstrate that a microfabricated bump array can concentrate genomic-length DNA molecules efficiently at continuous, high flow velocities, up to 40 μm/s, if the single-molecule DNA globule has a sufficiently large shear modulus. Increase in the shear modulus is accomplished by compacting the DNA molecules to minimal coil size using polyethylene glycol (PEG) derived depletion forces. We map out the sweet spot, where concentration occurs, as a function of PEG concentration and flow speed using a combination of theoretical analysis and experiment. Purification of DNA from enzymatic reactions for next-generation DNA-sequencing libraries will be an important application of this development.

Bos J, Zhang Q, Vyawahare Rogers Rosenberg SM Austin RH. SE. “Emergence of antibiotic resistance from multinucleated bacterial filaments.Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):178-83. doi: 10.1073/pnas.1420702111. Epub 2014 Dec 9. (2015). Publisher's VersionAbstract

Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here the first steps of this evolution in the bacterium Escherichia coli. Induction of the SOS response by the genotoxic antibiotic ciprofloxacin changes the E. coli rod shape into multichromosome-containing filaments. We show that at subminimal inhibitory concentrations of ciprofloxacin the bacterial filament divides asymmetrically repeatedly at the tip. Chromosome-containing buds are made that, if resistant, propagate nonfilamenting progeny with enhanced resistance to ciprofloxacin as the parent filament dies. We propose that the multinucleated filament creates an environmental niche where evolution can proceed via generation of improved mutant chromosomes due to the mutagenic SOS response and possible recombination of the new alleles between chromosomes. Our data provide a better understanding of the processes underlying the origin of resistance at the single-cell level and suggest an analogous role to the eukaryotic aneuploidy condition in cancer.

D'Silva J, Austin RH, Sturm JC.Inhibition of clot formation in deterministic lateral displacement arrays for processing large volumes of blood for rare cell capture.Lab Chip. 2015 May 21;15(10):2240-7. doi: 10.1039/c4lc01409j. (2015). Publisher's VersionAbstract

Microfluidic deterministic lateral displacement (DLD) arrays have been applied for fractionation and analysis of cells in quantities of ~100 μL of blood, with processing of larger quantities limited by clogging in the chip. In this paper, we (i) demonstrate that this clogging phenomenon is due to conventional platelet-driven clot formation, (ii) identify and inhibit the two dominant biological mechanisms driving this process, and (iii) characterize how further reductions in clot formation can be achieved through higher flow rates and blood dilution. Following from these three advances, we demonstrate processing of 14 mL equivalent volume of undiluted whole blood through a single DLD array in 38 minutes to harvest PC3 cancer cells with ~86% yield. It is possible to fit more than 10 such DLD arrays on a single chip, which would then provide the capability to process well over 100 mL of undiluted whole blood on a single chip in less than one hour.

Chen Y, D'Silva J, Austin RH Sturm JC.Microfluidic chemical processing with on-chip washing by deterministic lateral displacement arrays with separator walls.Biomicrofluidics. 2015 Sep 9;9(5):054105. doi: 10.1063/1.4930863. eCollection 2015 Sep. (2015). Publisher's VersionAbstract

We describe a microfluidic device for on-chip chemical processing, such as staining, and subsequent washing of cells. The paper introduces "separator walls" to increase the on-chip incubation time and to improve the quality of washing. Cells of interest are concentrated into a treatment stream of chemical reagents at the first separator wall for extended on-chip incubation without causing excess contamination at the output due to diffusion of the unreacted treatment chemicals, and then are directed to the washing stream before final collections. The second separator wall further reduces the output contamination from diffusion to the washing stream. With this approach, we demonstrate on-chip leukocyte staining with Rhodamine 6G and washing. The results suggest that other conventional biological and analytical processes could be replaced by the proposed device.

Lambert G, Vyawahare S, Austin RH.Bacteria and game theory: the rise and fall of cooperation in spatially heterogeneous environments.” Interface Focus. 2014 Aug 6;4(4):20140029. doi: 10.1098/rsfs.2014.0029. Review. (2014). Publisher's VersionAbstract

One of the predictions of game theory is that cooperative behaviours are vulnerable to exploitation by selfish individuals, but this result seemingly contradicts the survival of cooperation observed in nature. In this review, we will introduce game theoretical concepts that lead to this conclusion and show how the spatial competition dynamics between microorganisms can be used to model the survival and maintenance of cooperation. In particular, we focus on how Escherichia coli bacteria with a growth advantage in stationary phase (GASP) phenotype maintain a proliferative phenotype when faced with overcrowding to gain a fitness advantage over wild-type populations. We review recent experimental approaches studying the growth dynamics of competing GASP and wild-type strains of E. coli inside interconnected microfabricated habitats and use a game theoretical approach to analyse the observed inter-species interactions. We describe how the use of evolutionary game theory and the ideal free distribution accurately models the spatial distribution of cooperative and selfish individuals in spatially heterogeneous environments. Using bacteria as a model system of cooperative and selfish behaviours may lead to a better understanding of the competition dynamics of other organisms-including tumour-host interactions during cancer development and metastasis.

Wu A, Liao D, Tlsty TD Sturm JC Austin RH.Game theory in the death galaxy: interaction of cancer and stromal cells in tumour microenvironment.PMID: 25097749 (2014). Publisher's VersionAbstract

Preventing relapse is the major challenge to effective therapy in cancer. Within the tumour, stromal (ST) cells play an important role in cancer progression and the emergence of drug resistance. During cancer treatment, the fitness of cancer cells can be enhanced by ST cells because their molecular signalling interaction delays the drug-induced apoptosis of cancer cells. On the other hand, competition among cancer and ST cells for space or resources should not be ignored. We explore the population dynamics of multiple myeloma (MM) versus bone marrow ST cells by using an experimental microecology that we call the death galaxy, with a stable drug gradient and connected microhabitats. Evolutionary game theory is a quantitative way to capture the frequency-dependent nature of interactive populations. Therefore, we use evolutionary game theory to model the populations in the death galaxy with the gradients of pay-offs and successfully predict the future densities of MM and ST cells. We discuss the possible clinical use of such analysis for predicting cancer progression.

Vyawahare S, Zhang Q, Lau Austin RH. A. “In vitro microbial culture models and their application in drug development.Adv Drug Deliv Rev. 2014 Apr;69-70:217-24. doi: 10.1016/j.addr.2014.02.005. Epub 2014 Feb 21. (2014). Publisher's VersionAbstract

Drug development faces its nemesis in the form of drug resistance. The rate of bacterial resistance to antibiotics, or tumor resistance to chemotherapy decisively depends on the surrounding heterogeneous tissue. However, in vitro drug testing is almost exclusively done in well stirred, homogeneous environments. Recent advancements in microfluidics and microfabrication introduce opportunities to develop in vitro culture models that mimic the complex in vivo tissue environment. In this review, we will first discuss the design principles underlying such models. Then we will demonstrate two types of microfluidic devices that combine stressor gradients, cell motility, large population of competing/cooperative cells and time varying dosage of drugs. By incorporating ideas from how natural selection and evolution move drug resistance forward, we show that drug resistance can occur at much greater rates than in well-stirred environments. Finally, we will discuss the future direction of in vitro microbial culture models and how to extend the lessons learned from microbial systems to eukaryotic cells.

Sturm JC, Cox EC, Comella Austin RH. B. “Ratchets in hydrodynamic flow: more than waterwheels.Interface Focus. 2014 Dec 6;4(6):20140054. doi: 10.1098/rsfs.2014.0054. Review. (2014). Publisher's VersionAbstract

The transport of objects in microfluidic arrays of obstacles is a surprisingly rich area of physics and statistical mechanics. Tom Duke's mastery of these areas had a major impact in the development of biotechnology which uses these ideas at an increasing scale. We first review how biological objects are transported in fluids at low Reynolds numbers, including a discussion of electrophoresis, then concentrate on the separation of objects in asymmetric arrays, sometimes called Brownian ratchets when diffusional symmetry is broken by the structures. We move beyond this to what are called deterministic arrays where non-hydrodynamic forces in asymmetric arrays allow for extraordinary separation, and we look to the future of using these unusual arrays at the nanoscale and at the hundreds of micrometre scale. The emphasis is on how the original ideas of Tom Duke drove this work forward.

RH., Austin. “Rejoice in the hubris: useful things biologists could do for physicists.Phys Biol. 2014 Oct 8;11(5):053015. doi: 10.1088/1478-3975/11/5/053015. (2014). Publisher's VersionAbstract

Political correctness urges us to state how wonderful it is to work with biologists and how, just as the lion will someday lie down with the lamb, so will interdisciplinary work, where biologists and physicists are mixed together in light, airy buildings designed to force socialization, give rise to wonderful new science. But it has been said that the only drive in human nature stronger than the sex drive is the drive to censor and suppress, and so I claim that it is OK for physicists and biologists to maintain a wary distance from each other, so that neither one censors or suppresses the wild ideas of the other.

Kessler DA, Austin RH, Levine H. “Resistance to chemotherapy: patient variability and cellular heterogeneity.Cancer Res. 2014 Sep 1;74(17):4663-70. doi: 10.1158/0008-5472.CAN-14-0118. (2014). Publisher's VersionAbstract

The issue of resistance to targeted drug therapy is of pressing concern, as it constitutes a major barrier to progress in managing cancer. One important aspect is the role of stochasticity in determining the nature of the patient response. We examine two particular experiments. The first measured the maximal response of melanoma to targeted therapy before the resistance causes the tumor to progress. We analyze the data in the context of a Delbruck-Luria type scheme, wherein the continued growth of preexistent resistant cells are responsible for progression. We show that, aside from a finite fraction of resistant cell-free patients, the maximal response in such a scenario would be quite uniform. To achieve the measured variability, one is necessarily led to assume a wide variation from patient to patient of the sensitive cells' response to the therapy. The second experiment is an in vitro system of multiple myeloma cells. When subject to a spatial gradient of a chemotherapeutic agent, the cells in the middle of the system acquire resistance on a rapid (two-week) timescale. This finding points to the potential important role of cell-to-cell differences, due to differing local environments, in addition to the patient-to-patient differences encountered in the first part. See all articles in this Cancer Research section, "Physics in Cancer Research."

©2014 American Association for Cancer Research.

Zhang Q, Bos J, Tarnopolskiy Sturm JC Kim Pourmand Austin RH. GHN. “You cannot tell a book by looking at the cover: Cryptic complexity in bacterial evolution.Biomicrofluidics. 2014 Sep 9;8(5):052004. doi: 10.1063/1.4894410. eCollection 2014 Sep. (2014). Publisher's VersionAbstract

Do genetically closely related organisms under identical, but strong selection pressure converge to a common resistant genotype or will they diverge to different genomic solutions? This question gets at the heart of how rough is the fitness landscape in the local vicinity of two closely related strains under stress. We chose a Growth Advantage in Stationary Phase (GASP) E scherichia coli strain to address this question because the GASP strain has very similar fitness to the wild-type (WT) strain in the absence of metabolic stress but in the presence of metabolic stress continues to divide and does not enter into stationary phase. We find that under strong antibiotic selection pressure by the fluoroquinolone antibiotic ciprofloxacin in a complex ecology that the GASP strain rapidly evolves in under 20 h missense mutation in gyrA only 2 amino acids removed from the WT strain indicating a convergent solution, yet does not evolve the other 3 mutations of the WT strain. Further the GASP strain evolves a prophage e14 excision which completely inhibits biofilm formation in the mutant strain, revealing the hidden complexity of E. coli evolution to antibiotics as a function of selection pressure. We conclude that there is a cryptic roughness to fitness landscapes in the absence of stress.

Wu A, Loutherback K, Lambert Estévez-Salmerón Tlsty TD Austin RH Sturm JC. GL. “Cell motility and drug gradients in the emergence of resistance to chemotherapy.Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16103-8. doi: 10.1073/pnas.1314385110. Epub 2013 Sep 17. (2013). Publisher's VersionAbstract

The emergence of resistance to chemotherapy by cancer cells, when combined with metastasis, is the primary driver of mortality in cancer and has proven to be refractory to many efforts. Theory and computer modeling suggest that the rate of emergence of resistance is driven by the strong selective pressure of mutagenic chemotherapy and enhanced by the motility of mutant cells in a chemotherapy gradient to areas of higher drug concentration and lower population competition. To test these models, we constructed a synthetic microecology which superposed a mutagenic doxorubicin gradient across a population of motile, metastatic breast cancer cells (MDA-MB-231). We observed the emergence of MDA-MB-231 cancer cells capable of proliferation at 200 nM doxorubicin in this complex microecology. Individual cell tracking showed both movement of the MDA-MB-231 cancer cells toward higher drug concentrations and proliferation of the cells at the highest doxorubicin concentrations within 72 h, showing the importance of both motility and drug gradients in the emergence of resistance.

Liu L, Duclos G, Sun Lee Wu Kam Sontag ED Stone HA Sturm JC Gatenby RA Austin RH. BJAY. “Minimization of thermodynamic costs in cancer cell invasion.Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1686-91. doi: 10.1073/pnas.1221147110. Epub 2013 Jan 14. (2013). Publisher's VersionAbstract

Metastasis, the truly lethal aspect of cancer, occurs when metastatic cancer cells in a tumor break through the basement membrane and penetrate the extracellular matrix. We show that MDA-MB-231 metastatic breast cancer cells cooperatively invade a 3D collagen matrix while following a glucose gradient. The invasion front of the cells is a dynamic one, with different cells assuming the lead on a time scale of 70 h. The front cell leadership is dynamic presumably because of metabolic costs associated with a long-range strain field that precedes the invading cell front, which we have imaged using confocal imaging and marker beads imbedded in the collagen matrix. We suggest this could be a quantitative assay for an invasive phenotype tracking a glucose gradient and show that the invading cells act in a cooperative manner by exchanging leaders in the invading front.

Davis BH, Pan J, Tung CK Austin RH Riehn R. “SENSING DNA WITH ALTERNATING CURRENTS USING A NANOGAP SENSOR EMBEDDED IN A NANOCHANNEL DEVICE.Nano Life. 2013 Mar;3(1). doi: 10.1142/S1793984413400072. (2013). Publisher's VersionAbstract

We report an integrated nanochannel/nanoelectrode sensor for the detection of DNA using alternating currents. We find that DNA can be detected using platinum as the metal for the detecting electrodes, with a signal to noise ratio exceeding 10. We argue that the signal is at least in part electrochemical in nature, thus holds the promise to yield a sequence-dependent signal. However, we also find that for large voltages, DNA attaches irreversibly to the driving electrodes.

Oncology Centers Network, Agus DB, Alexander JF Arap Ashili Aslan JE Austin RH Backman Bethel KJ Bonneau Chen WC WSV. “A physical sciences network characterization of non-tumorigenic and metastatic cells.PMID: 23618955 [PubMed - indexed for MEDLINE] PMCID: PMC3636513 (2013). Publisher's VersionAbstract

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

Loutherback K1, D'Silva J, Liu Wu Austin RH Sturm JC. LA. “Deterministic separation of cancer cells from blood at 10 mL/min.AIP Adv. 2012 Dec;2(4):42107. Epub 2012 Oct 3. (2012). Publisher's VersionAbstract

Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters of cancer cells with their associated stroma cells. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement (DLD) arrays. We show here that a DLD array device can isolate CTCs from blood with capture efficiency greater than 85% CTCs at volumetric flow rates of up to 10 mL/min with no effect on cell viability.

Reisner W1, Pedersen JN, Austin RH.DNA confinement in nanochannels: physics and biological applications.Rep Prog Phys (2012). Publisher's VersionAbstract

DNA is the central storage molecule of genetic information in the cell, and reading that information is a central problem in biology. While sequencing technology has made enormous advances over the past decade, there is growing interest in platforms that can readout genetic information directly from long single DNA molecules, with the ultimate goal of single-cell, single-genome analysis. Such a capability would obviate the need for ensemble averaging over heterogeneous cellular populations and eliminate uncertainties introduced by cloning and molecular amplification steps (thus enabling direct assessment of the genome in its native state). In this review, we will discuss how the information contained in genomic-length single DNA molecules can be accessed via physical confinement in nanochannels. Due to self-avoidance interactions, DNA molecules will stretch out when confined in nanochannels, creating a linear unscrolling of the genome along the channel for analysis. We will first review the fundamental physics of DNA nanochannel confinement--including the effect of varying ionic strength--and then discuss recent applications of these systems to genomic mapping. Apart from the intense biological interest in extracting linear sequence information from elongated DNA molecules, from a physics view these systems are fascinating as they enable probing of single-molecule conformation in environments with dimensions that intersect key physical length-scales in the 1 nm to 100 µm range.

Zhang, Qiucen, and Robert H Austin. “Applications of Microfluidics in Stem Cell Biology.” Bionanoscience 2 (2012).
Zhang, Qiucen, and Robert H Austin. “Physics of Cancer: The Impact of Heterogeneity.” Annual Review of Condensed Matter Physics 5 (2012): 363-382.
Zhang, Qiucen, Kristelle Robin, David Liao, Guillaume Lambert, and Robert H Austin. “The Goldilocks Principle and Antibiotic Resistance in Bacteria.” Molecular Pharmaceutics 8 (2011). Abstract
Zhang, Qiucen, Guillaume Lambert, David Liao, Hyunsung Kim, Kristelle Robin, Chih-Kuan Tung, Nader Pourmand, and Robert H Austin. “Acceleration of Emergence of Bacterial Antibiotic Resistance in Connected Microenvironments.” Science 333 (2011): 1764-1767. Abstract
Lambert, Guillaume, Luis Estévez-Salmeron, Steve Oh, David Liao, Beverly M Emerson, Thea D Tlsty, and Robert H Austin. “An analogy between the evolution of drug resistance in bacterial communities and malignant tissues.” Nat Rev Cancer 11 (2011): 375-382.
Lambert, Guillaume, David Liao, Saurabh Vyawahare, and Robert H Austin. “Anomalous Spatial Redistribution of Competing Bacteria under Starvation Conditions.” J. Bacteriol 193 (2011): 1878-1883. Abstract
Zhou, Chunda, Walter W Reisner, Rory J Staunton, Amir Ashan, Robert H Austin, and Robert Riehn. “Collapse of {DNA} in ac Electric Fields.” Physical Review Letters 106, no. 248103 (2011). Abstract
Liu, Liyu, Bo Sun, Jonas N Pedersen, {Koh-Meng} Aw Yong, Robert H Getzenberg, Howard A Stone, and Robert H Austin. “Probing the invasiveness of prostate cancer cells in a {3D} microfabricated landscape.” Proceedings of the National Academy of Sciences 108 (2011): 6853-6856. Abstract
Budijono, Stephanie J, Jingning Shan, Nan Yao, Yutaka Miura, Thomas Hoye, Robert H Austin, Yiguang Ju, and Robert K Prud'homme. “Synthesis of Stable Block-Copolymer-Protected NaYF4:Yb3+, Er3+ Up-Converting Phosphor Nanoparticles.” CHEMISTRY OF MATERIALS 22 (2010): 311-318. DownloadAbstract
Lim, Shuang Fang, William S Ryu, and Robert H Austin. “Particle size dependence of the dynamic photophysical properties of NaYF4:Yb, Er nanocrystals.” OPTICS EXPRESS 18 (2010): 2309-2316. DownloadAbstract
Lambert, Guillaume, David Liao, and Robert H Austin. “Collective Escape of Chemotactic Swimmers through Microscopic Ratchets.” American Physical Society 104, no. Phys. Rev. Lett. (2010). DownloadAbstract
Morton, K, OKC Tsui, CK} Tung, JC Sturm, SY Chou, and R Austin. “The anti-lotus leaf effect in nanohydrodynamic bump arrays.” NEW JOURNAL OF PHYSICS 12 (2010). Abstract
Loutherback, K, KS Chou, J Newman, J Puchalla, RH Austin, and JC Sturm. “Improved performance of deterministic lateral displacement arrays with triangular posts.” MICROFLUIDICS AND NANOFLUIDICS 9 (2010): 1143-1149. Abstract
Austin, Robert H, Chih-Kuan Tung, Guillaume Lambert, David Liao, and Xiuqing Gong. “An introduction to micro-ecology patches.” CHEMICAL SOCIETY REVIEWS 39 (2010): 1049-1059. DownloadAbstract
Liu, Liyu, Kevin Loutherback, David Liao, David Yeater, Guillaume Lambert, Andre Estevez-Torres, James C Sturm, Getzenberg, and Robert H Austin. “A microfluidic device for continuous cancer cell culture and passage with hydrodynamic forces.” Lab on a Chip 10 (2010): 1807-1813. DownloadAbstract
Tung, Chih-Kuan, Robert Riehn, and Robert H Austin. “Complementary metal oxide semiconductor compatible fabrication and characterization of parylene-C covered nanofluidic channels with integrated nanoelectrodes.” BIOMICROFLUIDICS 3 (2009). DownloadAbstract
Ungun, Baris, Robert K Prud'homme, Stephanie J Budijono, Jingning Shan, Shuang Fang Lim, Yiguang Ju, and Robert Austin. “Nanofabricated upconversion nanoparticles for photodynamic therapy.” Optics Express 17 (2009): 80-86.Abstract nanofabricated-upconversion-nanoparticles-for-photodynamic-therapy.pdf
Loutherback, Kevin, Jason Puchalla, RH Austin, and James C Sturm. “Deterministic Microfluidic Ratchet.” Physical Review Letters 102 (2009). DownloadAbstract
Austin, Robert H. “Alwyn C. Scott, a subversive character in Biological Physics.” JOURNAL OF BIOLOGICAL PHYSICS 35 (2009): 1-3. Download
Austin, Robert H, Aihua Xie, Dan Fu, W Warren, Britta Redlich, and Lex van der Meer. “Tilting after Dutch windmills: probably no long-lived Davydov solitons in proteins.” JOURNAL OF BIOLOGICAL PHYSICS 35 (2009): 91-101. DownloadAbstract
Lim, Shuang Fang, Robert Riehn, Chih-Kuan Tung, William S Ryu, Rui Zhuo, Joanna Dalland, and Robert H Austin. “Upconverting Nanophosphors for Bioimaging.” NANOTECHNOLOGY 20 (2009). DownloadAbstract
Morton, KJ, K Loutherback, DW Inglis, OK Tsui, JC Sturm, SY Chou, and RH Austin. “Crossing microfluidic streamlines to lyse, label and wash cells.” Lab on a Chip 8, no. 9 (2008): 1448-1453. DownloadAbstract
Austin, RH. “Nanoscale hydrodynamics in the cell: balancing motorized transport with diffusion.” Hfsp Journal 2, no. 5 (2008): 262-265. DownloadAbstract
Austin, RH, and SF Lim. “The Sackler Colloquium on promises and perils in nanotechnology for medicine.” Proceedings of the National Academy of Sciences of the United States of America 105, no. 45 (2008): 17217-17221. DownloadAbstract
Xia, QF, KJ Morton, RH Austin, and SY Chou. “Sub-10 nm Self-Enclosed Self-Limited Nanofluidic Channel Arrays.” Nano Letters 8, no. 11 (2008): 3830-3833. DownloadAbstract
Morton, KJ, K Loutherback, DW Inglis, OK Tsui, JC Sturm, SY Chou, and RH Austin. “Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials.” Proceedings of the National Academy of Sciences of the United States of America 105, no. 21 (2008): 7434-7438. DownloadAbstract
Liao, D, P Galajda, R Riehn, R Ilic, JL Puchalla, HG Yu, HG Craighead, and RH Austin. “Single molecule correlation spectroscopy in continuous flow mixers with zero-mode waveguides.” Optics Express 16, no. 14 (2008): 10077-10090. DownloadAbstract
Inglis, DW, JA Davis, TJ Zieziulewicz, DA Lawrence, RH Austin, and JC Sturm. “Determining blood cell size using microfluidic hydrodynamics.” Journal of Immunological Methods 329, no. 1-2 (2008): 151-156. DownloadAbstract
Keymer, JE, P Galajda, G Lambert, D Liao, and RH Austin. “Computation of mutual fitness by competing bacteria.” Proceedings of the National Academy of Sciences of the United States of America 105, no. 51 (2008): 20269-20273. DownloadAbstract
Park, Sungsu, Hyejin Hwang, Seong-Won Nam, Fernando Martinez, Robert H Austin, and William S Ryu. “Enhanced Caenorhabditis elegans Locomotion in a Structured Microfluidic Environment.” PLoS ONE 3, no. e2550 (2008). DownloadAbstract
Galajda, P, JE Keymer, J Dalland, S Park, S Kou, and RH Austin. “Funnel ratchets in biology at low Reynolds number: choanotaxis.” Journal Of Modern Optics 55 (2008): 3413-3422. DownloadAbstract
Inglis, DW, KJ Morton, JA Davis, TJ Zieziulewicz, DA Lawrence, RH Austin, and JC Sturm. “Microfluidic device for label-free measurement of platelet activation.” Lab on a Chip 8, no. 6 (2008): 925-931. DownloadAbstract
Austin, R. “Nanofluidics - A fork in the nano-road.” Nature Nanotechnology 2, no. 2 (2007): 79-80. nanofluidics-a-fork-in-the-nano-road.pdf
Liang, XG, KJ Morton, RH Austin, and SY Chou. “Single sub-20 nm wide, centimeter-long nanofluidic channel fabricated by novel nanoimprint Mold fabrication and direct imprinting.” Nano Letters 7, no. 12 (2007): 3774-3780. DownloadAbstract
Galajda, P, JE Keymer, P Chaikin, and RH Austin. “A wall of funnels concentrates swimming bacteria.” Journal of Bacteriology 189, no. 23 (2007): 8704-8707. DownloadAbstract
Austin, R, and K Krishana. “New opportunities with VUV and soft-X-ray free electron lasers: Biological systems.” Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment (2007). DownloadAbstract
Riehn, R, RH Austin, and JC Sturm. “A nanofluidic railroad switch for DNA.” Nano Letters 6, no. 9 (2006): 1973-1976. DownloadAbstract
Davis, JA, DW Inglis, KJ Morton, DA Lawrence, LR Huang, SY Chou, JC Sturm, and RH Austin. “Deterministic hydrodynamics: Taking blood apart.” Proceedings of the National Academy of Sciences of the United States of America 103, no. 40 (2006): 14779-14784. DownloadAbstract
Keymer, JE, P Galajda, C Muldoon, S Park, and RH Austin. “Bacterial metapopulations in nanofabricated landscapes.” Proceedings of the National Academy of Sciences of the United States of America 103, no. 46 (2006): 17290-17295. DownloadAbstract
Metzler, R, W Reisner, R Riehn, R Austin, JO Tegenfeldt, and IM Sokolov. “Diffusion mechanisms of localised knots along a polymer.” Europhysics Letters 76, no. 4 (2006): 696-702. DownloadAbstract
Wang, YM, RH Austin, and EC Cox. “Single molecule measurements of repressor protein 1D diffusion on DNA.” Physical Review Letters 97, no. 4 (2006): 4. DownloadAbstract
Lim, SF, R Riehn, WS Ryu, N Khanarian, CK Tung, D Tank, and RH Austin. “In vivo and scanning electron microscopy imaging of upconverting nanophosphors in Caenorhabditis elegans.” Nano Letters 6, no. 2 (2006): 169-174. DownloadAbstract
Bakajin, G, E Fountain, K Morton, SY Chou, JC Sturm, and RH Austin. “Materials aspects in micro- and nanofluidic systems applied to biology.Mrs Bulletin 31, no. 2 (2006): 108-113.Abstract
Riehn, R, and RH Austin. “Wetting micro- and nanofluidic devices using supercritical water.” Analytical Chemistry 78, no. 16 (2006): 5933-5934.Abstract
Inglis, DW, R Riehn, JC Sturm, and RH Austin. “Microfluidic high gradient magnetic cell separation.” Journal of Applied Physics 99, no. 8 (2006): 3.Abstract
Inglis, DW, JA Davis, RH Austin, and JC Sturm. “Critical particle size for fractionation by deterministic lateral displacement.” Lab on a Chip 6, no. 5 (2006): 655-658.Abstract
Wang, YM, JO Tegenfeldt, J Sturm, and RH Austin. “Long-range interactions between transcription factors.” Nanotechnology 16, no. 10 (2005): 1993-1999.Abstract
Reisner, W, KJ Morton, R Riehn, YM Wang, ZN Yu, M Rosen, JC Sturm, SY Chou, E Frey, and RH Austin. “Statics and dynamics of single DNA molecules confined in nanochannels.” Physical Review Letters 94, no. 19 (2005): 4.Abstract
Riehn, R, MC Lu, YM Wang, SF Lim, EC Cox, and RH Austin. “Restriction mapping in nanofluidic devices.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 29 (2005): 10012-10016.Abstract
Wang, YM, JO Tegenfeldt, W Reisner, R Riehn, XJ Guan, L Guo, I Golding, EC Cox, J Sturm, and RH Austin. “Single-molecule studies of repressor-DNA interactions show long-range interactions.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 28 (2005): 9796-9801. DownloadAbstract
Galajda, P, J Puchalla, R Riehn, and RH Austin. “Studying protein reaction kinetics by fluorescence correlation spectroscopy in microfluidic mixers.” Febs Journal 272 (2005): 339.
Saez, A, B Ladoux, O du Roure, P Silberzan, A Buguin, P Chavrier, and RH Austin. “An array of micro fabricated pillars to map forces during epithelial cell migration.” Biophysical Journal 88 1 (2005): 518A.
du Roure, O, A Saez, A Buguin, RH Austin, P Chavrier, P Siberzan, and B Ladoux. “Force mapping in epithelial cell migration.” Proceedings of the National Academy of Sciences of the United States of America 102, no. 7 (2005): 2390-2395. DownloadAbstract
Austin, RH, AH Xie, L van der Meer, B Redlich, PA Lindgard, H Frauenfelder, and D Fu. “Picosecond thermometer in the amide I band of myoglobin.” Physical Review Letters 94, no. 12 (2005): 4. DownloadAbstract
Inglis, DW, R Riehn, RH Austin, and JC Sturm. “Continuous microfluidic immunomagnetic cell separation.” Applied Physics Letters 85, no. 21 (2004): 5093-5095. DownloadAbstract
Huang, LR, EC Cox, RH Austin, and JC Sturm. “Continuous particle separation through deterministic lateral displacement.” Science 304, no. 5673 (2004): 987-990.Abstract
Wei, CH, PH Tsao, W Farm, PK Wei, JO Tegenfeldt, and RH Austin. “Polarization dependence of light intensity distribution near a nanometric aluminum slit.” Journal of the Optical Society of America B-Optical Physics 21, no. 5 (2004): 1005-1012.Abstract
Austin, R. “Complete biosequence patent search: Mission impossible?Abstracts of Papers of the American Chemical Society 226 (2004): U702.
Tegenfeldt, JO, C Prinz, H Cao, S Chou, WW Reisner, R Riehn, YM Wang, EC Cox, JC Sturm, and Silberzan P et al.The dynamics of genomic-length DNA molecules in 100-nm channels.” Proceedings of the National Academy of Sciences of the United States of America 101, no. 30 (2004): 10979-10983.Abstract
Tegenfeldt, JO, H Cao, WW Reisner, C Prinz, RH Austin, SY Chou, EC Cox, and JC Sturm. “Stretching DNA in nanochannels.” Biophysical Journal 86, no. 1 (2004).
Zhang, Y, RH Austin, EC Cox, and NP Ong. “Comment on "Insulating Behavior of lambda-DNA on the Micron Scale" - Reply.” Physical Review Letters 93, no. 23 (2004).
Puchalla, J, D Adamek, and R Austin. “Towards measurement of the time-resolved heat release of protein conformation dynamics.” Chemical Physics 307, no. 2-3 (2004): 285-290.Abstract
Tegenfeldt, JO, C Prinz, H Cao, RL Huang, RH Austin, SY Chou, EC Cox, and JC Sturm. “Micro- and nanofluidics for DNA analysis.” Analytical and Bioanalytical Chemistry 378, no. 7 (2004): 1678-1692.Abstract
Xie, AH, L Kelemen, B Redlich, L van der Meer, and R Austin. “Picosecond visible/IR pump-probe dynamics of photoactive yellow protein.” In, 2004.Abstract
Austin, R. “Nanopores - The art of sucking spaghetti.” Nature Materials 2, no. 9 (2003): 567-568.
Park, S, PM Wolanin, EA Yuzbashyan, H Lin, NC Darnton, JB Stock, P Silberzan, and R Austin. “Influence of topology on bacterial social interaction.” Proceedings of the National Academy of Sciences of the United States of America 100, no. 24 (2003): 13910-13915.Abstract
Li, WL, JO Tegenfeldt, L Chen, RH Austin, SY Chou, PA Kohl, J Krotine, and JC Sturm. “Sacrificial polymers for nanofluidic channels in biological applications.” Nanotechnology 14, no. 6 (2003): 578-583.Abstract
Edwards, GS, RH Austin, FE Carroll, ML Copeland, ME Couprie, WE Gabella, RF Haglund, BA Hooper, MS Hutson, and Jansen ED et al.Free-electron-laser-based biophysical and biomedical instrumentation.” Review of Scientific Instruments 74, no. 7 (2003): 3207-3245.Abstract
Park, S, PM Wolanin, EA Yuzbashyan, P Silberzan, JB Stock, and RH Austin. “Motion to form a quorum.” Science 301, no. 5630 (2003): 188.
Gifford, SC, MG Frank, J Derganc, C Gabel, RH Austin, T Yoshida, and MW Bitensky. “Parallel microchannel-based measurements of individual erythrocyte areas and volumes.” Biophysical Journal 84, no. 2 (2003): 623-633.Abstract
Austin, RH, and SS Chan. “Of spherical cows, cloudy crystal balls, and proteins.” Biochemical and Biophysical Research Communications 312, no. 1 (2003): 215-221.Abstract
Huang, LR, EC Cox, RH Austin, and JC Sturm. “Tilted Brownian ratchet for DNA analysis.” Analytical Chemistry 75, no. 24 (2003): 6963-6967.Abstract
Austin, RH, AH Xie, L van der Meer, M Shinn, and G Neil. “Self-trapped states in proteins?Journal of Physics: Condensed Matter 15, no. 18 (2003).Abstract
Cabodi, M, YF Chen, SWP Turner, HG Craighead, and RH Austin. “Continuous separation of biomolecules by the laterally asymmetric diffusion array with out-of-plane sample injection.” Electrophoresis 23, no. 20 (2002): 3496-3503.Abstract
Huang, LR, JO Tegenfeldt, JJ Kraeft, JC Sturm, RH Austin, and EC Cox. “A DNA prism for high-speed continuous fractionation of large DNA molecules.” Nature Biotechnology 20, no. 10 (2002): 1048-1051.Abstract
Chou, CF, JO Tegenfeldt, O Bakajin, SS Chan, EC Cox, N Darnton, T Duke, and RH Austin. “Electrodeless dielectrophoresis of single- and double-stranded DNA.” Biophysical Journal 83, no. 4 (2002): 2170-2179.Abstract
Cao, H, JO Tegenfeldt, RH Austin, and SY Chou. “Gradient nanostructures for interfacing microfluidics and nanofluidics.” Applied Physics Letters 81, no. 16 (2002): 3058-3060.Abstract
Huang, LR, P Silberzan, JO Tegenfeldt, EC Cox, JC Sturm, RH Austin, and H Craighead. “Role of molecular size in ratchet fractionation.” Physical Review Letters 89, no. 17 (2002): 4.Abstract
Zhang, Y, RH Austin, J Kraeft, EC Cox, and NP Ong. “Insulating behavior of lambda-DNA on the micron scale.” Physical Review Letters 89, no. 19 (2002).Abstract
Austin, RH, JO Tegenfeldt, H Cao, SY Chou, and EC Cox. “Scanning the controls: Genomics and nanotechnology.” Ieee Transactions on Nanotechnology 1, no. 1 (2002): 12-18.Abstract
Cao, H, ZN Yu, J Wang, JO Tegenfeldt, RH Austin, E Chen, W Wu, and SY Chou. “Fabrication of 10 nm enclosed nanofluidic channels.” Applied Physics Letters 81, no. 1 (2002): 174-176.Abstract
Xie, AH, AFG van der Meer, and RH Austin. “Excited-state lifetimes of far-infrared collective modes in proteins.” Physical Review Letters 88, no. 1 (2002).Abstract