Bio


Tony Ricco received BS and PhD degrees in Chemistry from UC Berkeley (1980) and MIT (1984), respectively. In Sandia National Laboratories’ Microsensor R&D Department (1984 – 1998), he developed chemical microsensors and integrated microsystems. He was guest professor at the University of Heidelberg's Applied Physical Chemistry Institute (winter 1996 – 1997). From 1999 – 2003, he was ACLARA BioSciences’ Director of Microtechnologies and Materials, developing consumable plastic microfluidic systems for genetic analysis, high-throughput pharmaceutical discovery, proteomics, and pathogen detection. He directed Stanford’s National Center for Space Biological Technologies from 2004 – 2007; since 2007, he has served as NASA Ames Research Center’s Chief Technologist for Small Payloads while on assignment from Stanford University. From 2003 - 2016, he was a founding member, then adjunct professor, at the Biomedical Diagnostics Institute (BDI, Dublin City University), developing single-platform point-of-care medical diagnostic devices for platelet function, infectious disease, and cardiovascular health.

Dr. Ricco is co-author of some 400 presentations, 250 publications, and 20 patents. He is a Fellow of the American Institute for Medical & Biological Engineering (AIMBE) and of The Electrochemical Society (ECS), former president of ECS's Sensor Division, and, since 2004, Vice President of the Transducer Research Foundation (TRF). He has been an editor of the Journal of Microelectromechanical Systems (JMEMS) since 2000.

At NASA, Tony works with teams that develop, launch, and operate remote, autonomous bioanalytical and spectroscopy systems for fundamental space biological and astrobiological studies, serving as chief technologist for multiple successful "cubesat" spaceflight missions incorporating living organisms. He is presently adapting these spaceflight technologies to the challenge of searching for molecular indicators of the presence of life on our solar system's "icy worlds", in particular Europa, Enceladus, and Mars' permafrost regions.

Current Role at Stanford


On assignment to NASA Ames Research Center as Chief Technologist for Small Payloads

Education & Certifications


  • BS, UC Berkeley, Chemistry (1980)
  • PhD, MIT, Chemistry (1984)

All Publications


  • EcAMSat spaceflight measurements of the role of σs in antibiotic resistance of stationary phase Escherichia coli in microgravity. Life sciences in space research Padgen, M. R., Lera, M. P., Parra, M. P., Ricco, A. J., Chin, M. n., Chinn, T. N., Cohen, A. n., Friedericks, C. R., Henschke, M. B., Snyder, T. V., Spremo, S. M., Wang, J. H., Matin, A. C. 2020; 24: 18–24

    Abstract

    We report the results of the EcAMSat (Escherichia coli Antimicrobial Satellite) autonomous space flight experiment, investigating the role of σs in the development of antibiotic resistance in uropathogenic E. coli (UPEC) in microgravity (µ-g). The presence of σs, encoded by the rpoS gene, has been shown to increase antibiotic resistance in Earth gravity, but it was unknown if this effect occurs in µ-g. Two strains, wildtype (WT) UPEC and its isogenic ΔrpoS mutant, were grown to stationary phase aboard EcAMSat, an 11-kg small satellite, and in a parallel ground-based control experiment; cell growth rates for the two strains were found to be unaltered by µ-g. After starvation for over 24 h, stationary-phase cells were incubated with three doses of gentamicin (Gm), a common treatment for urinary tract infections (which have been reported in astronauts). Cellular metabolic activity was measured optically using the redox-based indicator alamarBlue (aB): both strains exhibited slower metabolism in µ-g, consistent with results from previous smallsat missions. The results also showed that µ-g did not enhance UPEC resistance to Gm; in fact, both strains were more susceptible to Gm in µ-g. It was also found, via a second ground-control experiment, that multi-week storage in the payload hardware stressed the cells, potentially obscuring small differential effects of the antibiotic between WT and mutant and/or between µ-g and ground. Overall, results showed that the ∆rpoS mutant was 34-37% less metabolically active than the WT for four different sets of conditions: ground without Gm, ground with Gm; µ-g without Gm, µ-g with Gm. We conclude therefore that the rpoS gene and its downstream products are important therapeutic targets for treating bacterial infections in space, much as they are on the ground.

    View details for DOI 10.1016/j.lssr.2019.10.007

    View details for PubMedID 31987476

  • Nanosatellites for Biology in Space: In Situ Measurement of Bacillus subtilis Spore Germination and Growth after 6 Months in Low Earth Orbit on the O/OREOS Mission. Life (Basel, Switzerland) Nicholson, W. L., Ricco, A. J. 2019; 10 (1)

    Abstract

    We report here complete 6-month results from the orbiting Space Environment Survivability of Living Organisms (SESLO) experiment. The world's first and only long-duration live-biology cubesat experiment, SESLO was executed by one of two 10-cm cube-format payloads aboard the 5.5-kg O/OREOS (Organism/Organic Exposure to Orbital Stresses) free-flying nanosatellite, which launched to a 72°-inclination, 650-km Earth orbit in 2010. The SESLO experiment measured the long-term survival, germination, metabolic, and growth responses of Bacillus subtilis spores exposed to microgravity and ionizing radiation including heavy-ion bombardment. A pair of radiation dosimeters (RadFETs, i.e., radiation-sensitive field-effect transistors) within the SESLO payload provided an in-situ dose rate estimate of 6-7.6 mGy/day throughout the mission. Microwells containing samples of dried spores of a wild-type B. subtilis strain and a radiation-sensitive mutant deficient in Non-Homologoous End Joining (NHEJ) were rehydrated after 14, 91, and 181 days in space with nutrient medium containing with the redox dye alamarBlue (aB), which changes color upon reaction with cellular metabolites. Three-color transmitted light intensity measurements of all microwells were telemetered to Earth within days of each 24-hour growth experiment. At 14 and 91 days, spaceflight samples germinated, grew, and metabolized significantly more slowly than matching ground-control samples, as measured both by aB reduction and optical density changes; these rate differences notwithstanding, the final optical density attained was the same in both flight and ground samples. After 181 days in space, spore germination and growth appeared hindered and abnormal. We attribute the differences not to an effect of the space environment per se, as both spaceflight and ground-control samples exhibited the same behavior, but to a pair of ~15-day thermal excursions, after the 91-day measurement and before the 181-day experiment, that peaked above 46 °C in the SESLO payload. Because the payload hardware operated nominally at 181 days, the growth issues point to heat damage, most likely to component(s) of the growth medium (RPMI 1640 containing aB) or to biocompatibility issues caused by heat-accelerated outgassing or leaching of harmful compounds from components of the SESLO hardware and electronics.

    View details for DOI 10.3390/life10010001

    View details for PubMedID 31905771

  • Dynamic platelet function is markedly different in patients with cancer compared to healthy donors PLATELETS Cowman, J., Richter, L., Walsh, R., Keegan, N., Tinago, W., Ricco, A. J., Hennessy, B. T., Kenny, D., Dunne, E. 2019; 30 (6): 737–42

    Abstract

    Despite a fivefold increased risk of thromboembolism in patients with cancer, the mechanism of arterial thromboembolism is poorly understood. To address this, we investigated platelet function in cancer patients and healthy controls using an assay that mimics the arterial vasculature. Blood samples from cancer patients (n = 36) and healthy controls (n = 22) were perfused through custom-made parallel-plate flow chambers coated with von Willebrand factor (VWF) under arterial shear (1,500 s-1). Multiparameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analyzed using custom-designed platelet-tracking software. Six measured parameters that characterize in detail the surface motion and surface binding of several hundred platelets per blood sample differed significantly in those with cancer from the healthy donors. In particular, it was found that patients with cancer had decreased numbers of platelets interacting, translocating and adhering to VWF. There were also reductions in the speed and distances that platelets traveled on VWF in comparison to healthy controls. Platelet function differed between those with early-stage cancer compared to those with later stage cancer. Patients with advanced cancer had an increased number of platelets stably adhering to VWF and greater platelet surface coverage after a given time of interaction. To the best of our knowledge, our results demonstrate for the first time that dynamic platelet function is markedly different in patients with cancer compared to healthy donors.

    View details for DOI 10.1080/09537104.2018.1513475

    View details for Web of Science ID 000475649100008

    View details for PubMedID 30252557

  • Quantitative Detection of Complex Mixtures using a Single Chemical Sensor: Analysis of Response Transients using Multi-Stage Estimation ACS SENSORS Sothivelr, K., Bender, F., Josse, F., Yaz, E. E., Ricco, A. J. 2019; 4 (6): 1682–90

    Abstract

    Most chemical sensors are only partially selective to any specific target analyte(s), making identification and quantification of analyte mixtures challenging, a problem often addressed using arrays of partially selective sensors. This work presents and experimentally verifies a signal-processing technique based on estimation theory for online identification and quantification of multiple analytes using only the response data collected from a single polymer-coated sensor device. The demonstrated technique, based on multiple stages of exponentially weighted recursive least-squares estimation (EW-RLSE), first determines which of the analytes included in the sensor response model are absent from the mixture being analyzed; these are then eliminated from the model prior to executing the final stage of EW-RLSE, in which the sample's constituent analytes are more accurately quantified. The overall method is based on a sensor response model with specific parameters describing each coating-analyte pair and requires no initial assumptions regarding the concentrations of the analytes in a given sample. The technique was tested using the measured responses of polymer-coated shear-horizontal surface acoustic wave devices to multi-analyte mixtures of benzene, toluene, ethylbenzene, xylenes, and 1,2,4-trimethylbenzene in water. The results demonstrate how this method accurately identifies and quantifies the analytes present in a sample using the measured response of just a single sensor device. This effective, simple, lower-cost alternative to sensor arrays needs no arduous training protocol, just measurement of the response characteristics of each individual target analyte and the likely interferents and/or classes thereof.

    View details for DOI 10.1021/acssensors.9b00564

    View details for Web of Science ID 000473827800028

    View details for PubMedID 31117366

  • Blood group alters platelet binding kinetics to von Willebrand factor and consequently platelet function BLOOD Dunne, E., Qi, Q. M., Shaqfeh, E. S., O'Sullivan, J. M., Schoen, I., Ricco, A. J., O'Donnell, J. S., Kenny, D. 2019; 133 (12): 1371–77
  • In Vitro Measurement and Modeling of Platelet Adhesion on VWF-Coated Surfaces in Channel Flow BIOPHYSICAL JOURNAL Qi, Q. M., Dunne, E., Oglesby, I., Schoen, I., Ricco, A. J., Kenny, D., Shaqfeh, E. G. 2019; 116 (6): 1136–51
  • DESIGN OF CHEMICAL SENSOR COATINGS BASED ON BLENDS OF A SINGLE POLYMER-PLASTICIZER PAIR FOR DETECTION OF SINGLE OR MULTI-ANALYTE AQUEOUS SOLUTIONS Post, N. D., Sothivelr, K., Bender, F., Josse, F., Ricco, A. J., Yaz, E. E., IEEE IEEE. 2019: 693–96
  • Obtaining Chemical Selectivity from a Single, Nonselective Sensing Film: Two-Stage Adaptive Estimation Scheme with Multiparameter Measurement to Quantify Mixture Components and Interferents ACS SENSORS Sothivelr, K., Bender, F., Josse, F., Yaz, E. E., Ricco, A. J. 2018; 3 (9): 1656–65

    Abstract

    A new approach is reported to detect and quantify the members of a group of small-aromatic-molecule target analytes: benzene, toluene, ethylbenzene, and xylenes (BTEX), dissolved in water, in the presence of interferents, using only the data collected from a single polymer-coated SH-SAW (shear horizontal surface acoustic wave) device and a two-stage adaptive estimation scheme. This technique is composed of exponentially weighted recursive least-squares estimation (EW-RLSE) and a bank of Kalman filters (BKFs) and does not require any prior knowledge of the initial concentration range of the target analytes. The proposed approach utilizes the transient sensor response to sorption and/or desorption of the analytes as well as the error range associated with the response time constants to provide more information about the analyte-specific interactions with the polymer film. The approach assumes that the sensor response to contaminated groundwater is a linear combination of the responses to the single target analytes, the interferents that interact with the selected polymer sensor coatings, and measurement noise. The proposed technique was tested using actual sensor responses to contaminated groundwater samples containing multiple BTEX compounds with concentrations ranging from 10 to 2000 parts per billion, as well as common interferents including ethanol, 1,2,4-trimethylbenzene, naphthalene, n-heptane, and MTBE (methyl tert-butyl ether). Estimated concentration values, accurate to ±10% for benzene/toluene and ±15% for ethylbenzene/xylenes, are obtained in near-real time. The utilization of sorption and/or desorption data enables detection and quantification of BTEX compounds with improved accuracy, high tolerance to measurement noise, and improved chemical selectivity.

    View details for DOI 10.1021/acssensors.8b00353

    View details for Web of Science ID 000446276300009

    View details for PubMedID 30117735

  • Payload hardware and experimental protocol development to enable future testing of the effect of space microgravity on the resistance to gentamicin of uropathogenic Escherichia coli and its sigma(s)-deficient mutant LIFE SCIENCES IN SPACE RESEARCH Matin, A. C., Wang, J., Keyhan, M., Singh, R., Benoit, M., Parra, M. P., Padgen, M. R., Ricco, A. J., Chin, M., Friedericks, C. R., Chinn, T. N., Cohen, A., Henschke, M. B., Snyder, T. V., Lera, M. P., Ross, S. S., Mayberry, C. M., Choi, S., Wu, D. T., Tan, M. X., Boone, T. D., Beasley, C. C., Piccini, M. E., Spremo, S. M. 2017; 15: 1–10

    Abstract

    Human immune response is compromised and bacteria can become more antibiotic resistant in space microgravity (MG). We report that under low-shear modeled microgravity (LSMMG), stationary-phase uropathogenic Escherichia coli (UPEC) become more resistant to gentamicin (Gm), and that this increase is dependent on the presence of σs (a transcription regulator encoded by the rpoS gene). UPEC causes urinary tract infections (UTIs), reported to afflict astronauts; Gm is a standard treatment, so these findings could impact astronaut health. Because LSMMG findings can differ from MG, we report preparations to examine UPEC's Gm sensitivity during spaceflight using the E. coli Anti-Microbial Satellite (EcAMSat) as a free-flying "nanosatellite" in low Earth orbit. Within EcAMSat's payload, a 48-microwell fluidic card contains and supports study of bacterial cultures at constant temperature; optical absorbance changes in cell suspensions are made at three wavelengths for each microwell and a fluid-delivery system provides growth medium and predefined Gm concentrations. Performance characterization is reported here for spaceflight prototypes of this payload system. Using conventional microtiter plates, we show that Alamar Blue (AB) absorbance changes can assess the Gm effect on E. coli viability, permitting telemetric transfer of the spaceflight data to Earth. Laboratory results using payload prototypes are consistent with wellplate and flask findings of differential sensitivity of UPEC and its ∆rpoS strain to Gm. if σs plays the same role in space MG as in LSMMG and Earth gravity, countermeasures discovered in recent Earth studies (aimed at weakening the UPEC antioxidant defense) to control UPEC infections would prove useful also in space flights. Further, EcAMSat results should clarify inconsistencies from previous space experiments on bacterial antibiotic sensitivity and other issues.

    View details for DOI 10.1016/j.lssr.2017.05.001

    View details for Web of Science ID 000416873500001

    View details for PubMedID 29198308

  • Platelet behaviour on von Willebrand Factor changes in pregnancy: Consequences of haemodilution and intrinsic changes in platelet function SCIENTIFIC REPORTS Cowman, J., Muellers, S., Dunne, E., Ralph, A., Ricco, A. J., Malone, F. D., Kenny, D. 2017; 7: 6354

    Abstract

    Platelet function in pregnancy is poorly understood. Previous studies of platelet function in pregnancy have used non-physiological assays of platelet function with conflicting results. This study using a physiological assay of platelet function investigated platelet interactions with von Willebrand Factor (VWF) in blood from healthy pregnant women and healthy non-pregnant controls. Blood samples (200 µl) from third-trimester pregnancies (n = 21) and non-pregnant controls (n = 21) were perfused through custom-made parallel-plate flow chambers coated with VWF under arterial shear (1,500 s-1). Multi-parameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analysed using custom-designed platelet-tracking software. Platelet interactions with VWF decreased in healthy third-trimester pregnant participants relative to controls. This effect is most likely due to haemodilution which occurs physiologically during pregnancy. Interestingly, platelets in blood from pregnant participants translocated more slowly on VWF under arterial-shear conditions. These decreases in platelet translocation speed were independent of haemodilution, suggesting intrinsic changes in platelet function with pregnancy.

    View details for DOI 10.1038/s41598-017-06959-6

    View details for Web of Science ID 000425906200001

    View details for PubMedID 28743915

    View details for PubMedCentralID PMC5527092

  • Space as a Tool for Astrobiology: Review and Recommendations for Experimentations in Earth Orbit and Beyond SPACE SCIENCE REVIEWS Cottin, H., Kotler, J., Billi, D., Cockell, C., Demets, R., Ehrenfreund, P., Elsaesser, A., d'Hendecourt, L., van Loon, J. A., Martins, Z., Onofri, S., Quinn, R. C., Rabbow, E., Rettberg, P., Ricco, A. J., Slenzka, K., de la Torre, R., de Vera, J., Westall, F., Carrasco, N., Fresneau, A., Kawaguchi, Y., Kebukawa, Y., Dara Nguyen, Poch, O., Saiagh, K., Stalport, F., Yamagishi, A., Yano, H., Klamm, B. A. 2017; 209 (1-4): 83–181
  • Earth as a Tool for Astrobiology-A European Perspective SPACE SCIENCE REVIEWS Martins, Z., Cottin, H., Kotler, J., Carrasco, N., Cockell, C. S., de la Torre Noetzel, R., Demets, R., de Vera, J., d'Hendecourt, L., Ehrenfreund, P., Elsaesser, A., Foing, B., Onofri, S., Quinn, R., Rabbow, E., Rettberg, P., Ricco, A. J., Slenzka, K., Stalport, F., ten Kate, I. L., van Loon, J. A., Westall, F. 2017; 209 (1-4): 43–81
  • An autonomous lab on a chip for space flight calibration of gravity-induced transcellular calcium polarization in single-cell fern spores LAB ON A CHIP Park, J., Salmi, M. L., Salim, W., Rademacher, A., Wickizer, B., Schooley, A., Benton, J., Cantero, A., Argote, P. F., Ren, M., Zhang, M., Porterfield, D. M., Ricco, A. J., Roux, S. J., Rickus, J. L. 2017; 17 (6): 1095–1103

    Abstract

    This report describes the development of lab-on-a-chip device designed to measure changes in cellular ion gradients that are induced by changes in gravitational (g) forces. The bioCD presented here detects differential calcium ion concentrations outside of individual cells. The device includes sufficient replicates for statistical analysis of the gradients around multiple single cells and around control wells that are empty or include dead cells. In the data presented, the degree of the cellular response correlates with the magnitude of the g-force applied via rotation of the bioCD. The experiments recorded the longest continuous observation of a cellular response to hypergravity made to date, and they demonstrate the potential utility of this device for assaying the threshold of cells' g-force responses in spaceflight conditions.

    View details for DOI 10.1039/c6lc01370h

    View details for Web of Science ID 000398571600012

    View details for PubMedID 28205656

  • Microgravity validation of a novel system for RNA isolation and multiplex quantitative real time PCR analysis of gene expression on the International Space Station. PloS one Parra, M. n., Jung, J. n., Boone, T. D., Tran, L. n., Blaber, E. A., Brown, M. n., Chin, M. n., Chinn, T. n., Cohen, J. n., Doebler, R. n., Hoang, D. n., Hyde, E. n., Lera, M. n., Luzod, L. T., Mallinson, M. n., Marcu, O. n., Mohamedaly, Y. n., Ricco, A. J., Rubins, K. n., Sgarlato, G. D., Talavera, R. O., Tong, P. n., Uribe, E. n., Williams, J. n., Wu, D. n., Yousuf, R. n., Richey, C. S., Schonfeld, J. n., Almeida, E. A. 2017; 12 (9): e0183480

    Abstract

    The International Space Station (ISS) National Laboratory is dedicated to studying the effects of space on life and physical systems, and to developing new science and technologies for space exploration. A key aspect of achieving these goals is to operate the ISS National Lab more like an Earth-based laboratory, conducting complex end-to-end experimentation, not limited to simple microgravity exposure. Towards that end NASA developed a novel suite of molecular biology laboratory tools, reagents, and methods, named WetLab-2, uniquely designed to operate in microgravity, and to process biological samples for real-time gene expression analysis on-orbit. This includes a novel fluidic RNA Sample Preparation Module and fluid transfer devices, all-in-one lyophilized PCR assays, centrifuge, and a real-time PCR thermal cycler. Here we describe the results from the WetLab-2 validation experiments conducted in microgravity during ISS increment 47/SPX-8. Specifically, quantitative PCR was performed on a concentration series of DNA calibration standards, and Reverse Transcriptase-quantitative PCR was conducted on RNA extracted and purified on-orbit from frozen Escherichia coli and mouse liver tissue. Cycle threshold (Ct) values and PCR efficiencies obtained on-orbit from DNA standards were similar to Earth (1 g) controls. Also, on-orbit multiplex analysis of gene expression from bacterial cells and mammalian tissue RNA samples was successfully conducted in about 3 h, with data transmitted within 2 h of experiment completion. Thermal cycling in microgravity resulted in the trapping of gas bubbles inside septa cap assay tubes, causing small but measurable increases in Ct curve noise and variability. Bubble formation was successfully suppressed in a rapid follow-up on-orbit experiment using standard caps to pressurize PCR tubes and reduce gas release during heating cycles. The WetLab-2 facility now provides a novel operational on-orbit research capability for molecular biology and demonstrates the feasibility of more complex wet bench experiments in the ISS National Lab environment.

    View details for PubMedID 28877184

    View details for PubMedCentralID PMC5587110

  • Investigation of Polymer-Plasticizer Blends as SH-SAW Sensor Coatings for Detection of Benzene in Water with High Sensitivity and Long-Term Stability ACS SENSORS Adhikari, P., Alderson, L., Bender, F., Ricco, A. J., Josse, F. 2017; 2 (1): 157–64

    Abstract

    We report the first-ever direct detection of benzene in water at concentrations below 100 ppb (parts per billion) using acoustic wave (specifically, shear-horizontal surface acoustic wave, SH-SAW) sensors with plasticized polymer coatings. Two polymers and two plasticizers were studied as materials for sensor coatings. For each polymer-plasticizer combination, the influence of the mixing ratio of the blend on the sensitivity to benzene was measured and compared to commercially available polymers that were used for BTEX (benzene, toluene, ethylbenzene, and xylene) detection in previous work. After optimizing the coating parameters, the highest sensitivity and lowest detection limit for benzene were found for a 1.25 μm thick sensor coating of 17.5%-by-weight diisooctyl azelate-polystyrene on the tested acoustic wave device. The calculated detection limit was 45 ppb, with actual sensor responses to concentrations down to 65 ppb measured directly. Among the sensor coatings that showed good sensitivity to benzene, the best long-term stability was found for a 1.0 μm thick coating of 23% diisononyl cyclohexane-1,2-dicarboxylate-polystyrene, which was studied here because it is known to show no detectable leaching in water. The present work demonstrates that, by varying type of plasticizer, mixing ratio, and coating thickness, the mechanical and chemical properties of the coatings can be conveniently tailored to maximize analyte sorption and partial chemical selectivity for a given class of analytes as well as to minimize acoustic-wave attenuation in contact with an aqueous phase at the operating frequency of the sensor device.

    View details for DOI 10.1021/acssensors.6b00659

    View details for Web of Science ID 000393088300021

    View details for PubMedID 28722439

  • Computational Tracking of Shear-Mediated Platelet Interactions with von Willebrand Factor CARDIOVASCULAR ENGINEERING AND TECHNOLOGY Ralph, A., Somers, M., Cowman, J., Voisin, B., Hogan, E., Dunne, H., Dunne, E., Byrne, B., Kent, N., Ricco, A. J., Kenny, D., Wong, S. 2016; 7 (4): 389–405

    Abstract

    The imaging of shear-mediated dynamic platelet behavior interacting with surface-immobilized von Willebrand factor (vWF) has tremendous potential in characterizing changes in platelet function for clinical diagnostics purposes. However, the imaging output, a series of images representing platelets adhering and rolling on the surface, poses unique, non-trivial challenges for software algorithms that reconstruct the positional trajectories of platelets. We report on an algorithm that tracks platelets using the output of such flow run experiments, taking into account common artifacts encountered by previously-published methods, and we derive seven key metrics of platelet dynamics that can be used to characterize platelet function. Extensive testing of our method using simulated platelet flow run data was carried out to validate our tracking method and derived metrics in capturing key platelet-vWF interaction-dynamics properties. Our results show that while the number of platelets present on the imaged area is the leading cause of errors, flow run data from two experiments using whole blood samples showed that our method and metrics can detect platelet property changes/differences that are concordant with the expected biological outcome, such as inhibiting key platelet receptors such as P2Y1, glycoprotein (GP)Ib and GPIIb/IIIa. These findings support the use of our methodologies to characterize platelet function among a wide range of healthy and disease cohorts.

    View details for DOI 10.1007/s13239-016-0282-x

    View details for Web of Science ID 000389342700005

    View details for PubMedID 27743349

  • Dynamic platelet function on von Willebrand factor is different in preterm neonates and full-term neonates: changes in neonatal platelet function JOURNAL OF THROMBOSIS AND HAEMOSTASIS Cowman, J., Quinn, N., Geoghegan, S., Mullers, S., Oglesby, I., Byrne, B., Somers, M., Ralph, A., Voisin, B., Ricco, A. J., Molloy, E. J., Kenny, D. 2016; 14 (10): 2027–35

    Abstract

    Essentials It is unclear if platelet function differs between preterm and full-term neonates. Platelet behavior was characterized using a flow-based assay on von Willebrand Factor (VWF). Preterms had increased platelet interaction with VWF and glycoprotein Ibα expression. Platelets from preterm neonates behave differently on VWF compared to full-term neonates.Background Very low birth weight (VLBW) preterm neonates have an increased risk of hemorrhage-related morbidity and mortality as compared with their full-term counterparts. It is unclear whether platelet function differs between preterm and full-term neonates. This is partly because of the large volumes of blood required to perform standard platelet function tests, and the difficulty in obtaining such samples in neonates. Objectives This study was designed to characterize platelet behavior in neonates with a physiologic flow-based assay that quantifies platelet function in microliter volumes of blood under arterial shear. Methods Blood from VLBW preterm neonates of ≤ 32 weeks' gestation (n = 15) and full-term neonates (n = 13) was perfused under arterial shear over surface-immobilized von Willebrand factor (VWF). Platelet behavior was recorded by digital-image microscopy and analyzed. Surface expression of platelet glycoprotein (GP) Ibα and GPIIIa of VLBW preterm and full-term neonates was also measured. Results VLBW preterm neonates had increased numbers of platelets interacting with VWF, and increased GPIbα expression on the platelet surface. Despite the increased numbers of VWF interactions as reflected by flow-driven platelet translocation along the protein surface, no significant differences were observed in the numbers of platelets that adhered in a stationary fashion to VWF. Platelets from VLBW preterm neonates and those from full-term neonates behaved differently on VWF. Conclusions These differences in platelet function may contribute to the higher incidence of bleeding observed in VLBW preterm neonatal populations, or may represent a compensatory mechanism to counteract this risk of bleeding.

    View details for DOI 10.1111/jth.13414

    View details for Web of Science ID 000386956200016

    View details for PubMedID 27416003

  • Self-Powered Microfluidic Device for Rapid Assay of Antiplatelet Drugs LANGMUIR Jose, B., McCluskey, P., Gilmartin, N., Somers, M., Kenny, D., Ricco, A. J., Kent, N. J., Basabe-Desmonts, L. 2016; 32 (11): 2820-2828

    Abstract

    We report the development of a microfluidic device for the rapid assay in whole blood of interfacial platelet-protein interactions indicative of the efficacy of antiplatelet drugs, for example, aspirin and Plavix, two of the world's most widely used drugs, in patients with cardiovascular disease (CVD). Because platelet adhesion to surface-confined protein matrices is an interfacial phenomenon modulated by fluid shear rates at the blood/protein interface, and because such binding is a better indicator of platelet function than platelet self-aggregation, we designed, fabricated, and characterized the performance of a family of disposable, self-powered microfluidic chips with well-defined flow and interfacial shear rates suitable for small blood volumes (≤200 μL). This work demonstrates that accurate quantification of cell adhesion to protein matrices, an important interfacial biological phenomenon, can be used as a powerful diagnostic tool in those with CVD, the world's leading cause of death. To enable such measurements, we developed a simple technique to fabricate single-use self-powered chips incorporating shear control (SpearChips). These parallel-plate flow devices integrate on-chip vacuum-driven blood flow, using a predegassed elastomer component to obviate active pumping, with microcontact-printed arrays of 6-μm-diameter fluorescently labeled fibrinogen dots on a cyclic olefin polymer base plate as a means to quantitatively count platelet-protein binding events. The use of SpearChips to assess in whole blood samples the effects of GPIIb/IIIa and P2Y12 inhibitors, two important classes of "antiplatelet" drugs, is reported.

    View details for DOI 10.1021/acs.langmuir.5b03540

    View details for Web of Science ID 000372856800033

    View details for PubMedID 26910300

  • Online Chemical Sensor Signal Processing Using Estimation Theory: Quantification of Binary Mixtures of Organic Compounds in the Presence of Linear Baseline Drift and Outliers IEEE SENSORS JOURNAL Sothivelr, K., Bender, F., Josse, F., Yaz, E. E., Ricco, A. J., Mohler, R. E. 2016; 16 (3): 750-761
  • Click Chemistry as an Immobilization Method to Improve Oligonucleotide Hybridization Efficiency for Nucleic Acid Assays Sensors and Actuators B: Chemical McKenna, M., Soberon, F., Ricco, A. J., Daniels, S., Kelleher, S. M. 2016; 236: 286-293
  • Detection and Quantification of Aromatic Hydrocarbon Compounds in Water Using SH-SAW Sensors and Estimation-Theory-Based Signal Processing ACS Sensors Sothivelr, K., Bender, F., Josse, F., Ricco, A. J., Yaz, E. E., Mohler, R. E., Kolhatkar, R. 2016; 1: 63-72
  • Examining platelet adhesion via Stokes flow simulations and microfluidic experiments. Soft matter FitzGibbon, S., Cowman, J., Ricco, A. J., Kenny, D., Shaqfeh, E. S. 2015; 11 (2): 355-367

    Abstract

    While critically important, the platelet function at the high shear rates typical of the microcirculation is relatively poorly understood. Using a large scale Stokes flow simulation, Zhao et al. recently showed that RBC-induced velocity fluctuations cause platelets to marginate into the RBC free near-wall region [Zhao et al., Physics of Fluids, 2012, 24, 011902]. We extend their work by investigating the dynamics of platelets in shear after margination. An overall platelet adhesion model is proposed in terms of a continuous time Markov process and the transition rates are established with numerical simulations involving platelet-wall adhesion. Hydrodynamic drag and Brownian forces are calculated with the boundary element method, while the RBC collisions are incorporated through an autoregressive process. Hookean springs with first order bond kinetics are used to model receptor-ligand bonds formed between the platelet and the wall. The simulations are compared with in vitro microfluidic experiments involving platelet adhesion to Von Willebrand Factor (VWF) coated surfaces.

    View details for DOI 10.1039/c4sm01450b

    View details for PubMedID 25382632

  • Age-related changes in platelet function are more profound in women than in men. Scientific reports Cowman, J., Dunne, E., Oglesby, I., Byrne, B., Ralph, A., Voisin, B., Müllers, S., Ricco, A. J., Kenny, D. 2015; 5: 12235-?

    Abstract

    Age is a risk factor for cardiovascular disease (CVD), however the effect of age on platelet function remains unclear. Ideally, platelet function should be assayed under flow and shear conditions that occur in vivo. Our study aimed to characterise the effect of age on platelet translocation behaviour using a novel flow-based assay that measures platelet function in less than 200 μl of blood under conditions of arterial shear. Blood from males (n = 53) and females (n = 56), ranging in age from 19-82 and 21-70 respectively were perfused through custom-made parallel plate flow chambers coated with immobilised human von Willebrand Factor (VWF) under arterial shear (1,500 s(-1)). Platelet translocation behaviour on VWF was recorded by digital-image microscopy and analysed. The study showed that aging resulted in a significant decrease in the number of platelet tracks, translocating platelets and unstable platelet interactions with VWF. These age related changes in platelet function were more profound in women than in men indicating that age and gender significantly impacts on platelet interactions with VWF.

    View details for DOI 10.1038/srep12235

    View details for PubMedID 26179119

    View details for PubMedCentralID PMC4503960

  • Examining platelet adhesion via Stokes flow simulations and microfluidic experiments SOFT MATTER FitzGibbon, S., Cowman, J., Ricco, A. J., Kenny, D., Shaqfeh, E. S. 2015; 11 (2): 355-367

    Abstract

    While critically important, the platelet function at the high shear rates typical of the microcirculation is relatively poorly understood. Using a large scale Stokes flow simulation, Zhao et al. recently showed that RBC-induced velocity fluctuations cause platelets to marginate into the RBC free near-wall region [Zhao et al., Physics of Fluids, 2012, 24, 011902]. We extend their work by investigating the dynamics of platelets in shear after margination. An overall platelet adhesion model is proposed in terms of a continuous time Markov process and the transition rates are established with numerical simulations involving platelet-wall adhesion. Hydrodynamic drag and Brownian forces are calculated with the boundary element method, while the RBC collisions are incorporated through an autoregressive process. Hookean springs with first order bond kinetics are used to model receptor-ligand bonds formed between the platelet and the wall. The simulations are compared with in vitro microfluidic experiments involving platelet adhesion to Von Willebrand Factor (VWF) coated surfaces.

    View details for DOI 10.1039/c4sm01450b

    View details for Web of Science ID 000346060400015

  • Fabrication and characterisation of spin coated oxidised PMMA to provide a robust surface for on-chip assays JOURNAL OF MATERIALS CHEMISTRY B Rowinska, M., Kelleher, S. M., Soberon, F., Ricco, A. J., Daniels, S. 2015; 3 (1): 135-143

    View details for DOI 10.1039/c4tb01748j

    View details for Web of Science ID 000346003300018

  • Analysis of Binary Mixtures of Aqueous Aromatic Hydrocarbons with Low-Phase-Noise Shear-Horizontal Surface Acoustic Wave Sensors Using Multielectrode Transducer Designs ANALYTICAL CHEMISTRY Bender, F., Mohler, R. E., Ricco, A. J., Josse, F. 2014; 86 (22): 11464-11471

    Abstract

    The present work investigates a compact sensor system that provides rapid, real-time, in situ measurements of the identities and concentrations of aromatic hydrocarbons at parts-per-billion concentrations in water through the combined use of kinetic and thermodynamic response parameters. The system uses shear-horizontal surface acoustic wave (SH-SAW) sensors operating directly in the liquid phase. The 103 MHz SAW sensors are coated with thin sorbent polymer films to provide the appropriate limits of detection as well as partial selectivity for the analytes of interest, the BTEX compounds (benzene, toluene, ethylbenzene, and xylenes), which are common indicators of fuel and oil accidental releases in groundwater. Particular emphasis is placed on benzene, a known carcinogen and the most challenging BTEX analyte with regard to both regulated levels and its solubility properties. To demonstrate the identification and quantification of individual compounds in multicomponent aqueous samples, responses to binary mixtures of benzene with toluene as well as ethylbenzene were characterized at concentrations below 1 ppm (1 mg/L). The use of both thermodynamic and kinetic (i.e., steady-state and transient) responses from a single polymer-coated SH-SAW sensor enabled identification and quantification of the two BTEX compounds in binary mixtures in aqueous solution. The signal-to-noise ratio was improved, resulting in lower limits of detection and improved identification at low concentrations, by designing and implementing a type of multielectrode transducer pattern, not previously reported for chemical sensor applications. The design significantly reduces signal distortion and root-mean-square (RMS) phase noise by minimizing acoustic wave reflections from electrode edges, thus enabling limits of detection for BTEX analytes of 9-83 ppb (calculated from RMS noise); concentrations of benzene in water as low as ~100 ppb were measured directly. Reliable quantification of BTEX analytes in binary mixtures is demonstrated in the sub-parts-per-million concentration range.

    View details for DOI 10.1021/ac503701b

    View details for Web of Science ID 000345263300068

    View details for PubMedID 25346184

  • Organics Exposure in Orbit (OREOcube): A Next-Generation Space Exposure Platform LANGMUIR Elsaesser, A., Quinn, R. C., Ehrenfreund, P., Mattioda, A. L., Ricco, A. J., Alonzo, J., Breitenbach, A., Chan, Y. K., Fresneau, A., Salama, F., Santos, O. 2014; 30 (44): 13217-13227

    Abstract

    The OREOcube (ORganics Exposure in Orbit cube) experiment on the International Space Station (ISS) will investigate the effects of solar and cosmic radiation on organic thin films supported on inorganic substrates. Probing the kinetics of structural changes and photomodulated organic-inorganic interactions with real-time in situ UV-visible spectroscopy, this experiment will investigate the role played by solid mineral surfaces in the (photo)chemical evolution, transport, and distribution of organics in our solar system and beyond. In preparation for the OREOcube ISS experiment, we report here laboratory measurements of the photostability of thin films of the 9,10-anthraquinone derivative anthrarufin (51 nm thick) layered upon ultrathin films of iron oxides magnetite and hematite (4 nm thick), as well as supported directly on fused silica. During irradiation with UV and visible light simulating the photon flux and spectral distribution on the surface of Mars, anthrarufin/iron oxide bilayer thin films were exposed to CO2 (800 Pa), the main constituent (and pressure) of the martian atmosphere. The time-dependent photodegradation of anthrarufin thin films revealed the inhibition of degradation by both types of underlying iron oxides relative to anthrarufin on bare fused silica. Interactions between the organic and inorganic thin films, apparent in spectral shifts of the anthrarufin bands, are consistent with presumed free-electron quenching of semiquinone anion radicals by the iron oxide layers, effectively protecting the organic compound from photodegradation. Combining such in situ real-time kinetic measurements of thin films in future space exposure experiments on the ISS with postflight sample return and analysis will provide time-course studies complemented by in-depth chemical analysis. This will facilitate the characterization and modeling of the chemistry of organic species associated with mineral surfaces in astrobiological contexts.

    View details for DOI 10.1021/la501203g

    View details for Web of Science ID 000344905100012

    View details for PubMedID 24851720

  • Three-Dimensional Wax Patterning of Paper Fluidic Devices LANGMUIR Renault, C., Koehne, J., Ricco, A. J., Crooks, R. M. 2014; 30 (23): 7030-7036

    Abstract

    In this paper we describe a method for three-dimensional wax patterning of microfluidic paper-based analytical devices (μPADs). The method is rooted in the fundamental details of wax transport in paper and provides a simple way to fabricate complex channel architectures such as hemichannels and fully enclosed channels. We show that three-dimensional μPADs can be fabricated with half as much paper by using hemichannels rather than ordinary open channels. We also provide evidence that fully enclosed channels are efficiently isolated from the exterior environment, decreasing contamination risks, simplifying the handling of the device, and slowing evaporation of solvents.

    View details for DOI 10.1021/la501212b

    View details for Web of Science ID 000337644200048

    View details for PubMedID 24896490

  • Identification and Quantification of Aqueous Aromatic Hydrocarbons Using SH-Surface Acoustic Wave Sensors ANALYTICAL CHEMISTRY Bender, F., Mohler, R. E., Ricco, A. J., Josse, F. 2014; 86 (3): 1794-1799

    Abstract

    A need exists for compact sensor systems capable of in situ monitoring of groundwater for accidental releases of fuel and oil. The work reported here addresses this need, using shear horizontal surface acoustic wave (SH-SAW) sensors, which function effectively in liquid environments. To achieve enhanced sensitivity and partial selectivity for hydrocarbons, the devices are coated with thin chemically sensitive polymer films. Various polymer materials are investigated with the goal of identifying a set of coatings suitable for a sensor array. The system is tested with compounds indicative of fuel and oil releases, in particular, the BTEX compounds (benzene, toluene, ethylbenzene, and xylenes), in the low milligrams/liters to high micrograms/liters concentration range. Particular emphasis is placed on detection of benzene, a known carcinogen. It was observed that within the above concentration range, responses to multiple analytes in a mixture are additive, and there is a characteristic response time for each coating/analyte pair, which is largely independent of concentration. With the use of both the steady-state and transient-response information of SH-SAW sensor devices coated with three different polymer materials, poly(ethyl acrylate), poly(epichlorohydrin), and poly(isobutylene), a response pattern was obtained for benzene that is easily distinguishable from those of the other BTEX compounds. The time courses of the responses to binary analyte mixtures were modeled accurately using dual-exponential fits, yielding a characteristic concentration-independent time constant for each analyte/coating pair. Benzene concentration was quantified in the aqueous phase in the presence of the other BTEX compounds.

    View details for DOI 10.1021/ac403724f

    View details for Web of Science ID 000331014800066

    View details for PubMedID 24392747

  • The Organism/Organic Exposure to Orbital Stresses (O/OREOS) Satellite: Radiation Exposure in Low-Earth Orbit and Supporting Laboratory Studies of Iron Tetraphenylporphyrin Chloride ASTROBIOLOGY Cook, A. M., Mattioda, A. L., Ricco, A. J., Quinn, R. C., Elsaesser, A., Ehrenfreund, P., Ricca, A., Jones, N. C., Hoffmann, S. V. 2014; 14 (2): 87-101

    Abstract

    We report results from the exposure of the metalloporphyrin iron tetraphenylporphyrin chloride (FeTPPCl) to the outer space environment, measured in situ aboard the Organism/Organic Exposure to Orbital Stresses nanosatellite. FeTPPCl was exposed for a period of 17 months (3700 h of direct solar exposure), which included broad-spectrum solar radiation (∼122 nm to the near infrared). Motivated by the potential role of metalloporphyrins as molecular biomarkers, the exposure of thin-film samples of FeTPPCl to the space environment in low-Earth orbit was monitored in situ via ultraviolet/visible spectroscopy and reported telemetrically. The space data were complemented by laboratory exposure experiments that used a high-fidelity solar simulator covering the spectral range of the spaceflight measurements. We found that thin-film samples of FeTPPCl that were in contact with a humid headspace gas (0.8-2.3% relative humidity) were particularly susceptible to destruction upon irradiation, degrading up to 10 times faster than identical thin films in contact with dry headspace gases; this degradation may also be related to the presence of oxides of nitrogen in those cells. In the companion terrestrial experiments, simulated solar exposure of FeTPPCl films in contact with either Ar or CO2:O2:Ar (10:0.01:1000) headspace gas resulted in growth of a band in the films' infrared spectra at 1961 cm(-1). We concluded that the most likely carriers of this band are allene (C3H4) and chloropropadiene (C3H3Cl), putative molecular fragments of the destruction of the porphyrin ring. The thin films studied in space and in solar simulator-based experiments show qualitatively similar spectral evolution as a function of contacting gaseous species but display significant differences in the time dependence of those changes. The relevance of our findings to planetary science, biomarker research, and the photostability of organic materials in astrobiologically relevant environments is discussed.

    View details for DOI 10.1089/ast.2013.0998

    View details for Web of Science ID 000331460600002

    View details for PubMedID 24512475

  • SEVO ON THE GROUND: DESIGN OF A LABORATORY SOLAR SIMULATION IN SUPPORT OF THE O/OREOS MISSION ASTROPHYSICAL JOURNAL SUPPLEMENT SERIES Cook, A. M., Mattioda, A. L., Quinn, R. C., Ricco, A. J., Ehrenfreund, P., Bramall, N. E., Minelli, G., Quigley, E., Walker, R., Walker, R. 2014; 210 (2)
  • The O/OREOS mission-Astrobiology in low Earth orbit ACTA ASTRONAUTICA Ehrenfreund, P., Ricco, A. J., Squires, D., Kitts, C., Agasid, E., Bramall, N., Bryson, K., Chittenden, J., Conley, C., Cook, A., Mancinelli, R., Mattioda, A., Nicholson, W., Quinn, R., Santos, O., Tahu, G., VOYTEK, M., Beasley, C., Bica, L., Diaz-Aguado, M., Friedericks, C., Henschke, M., Landis, D., Luzzi, E., Ly, D., Mai, N., Minelli, G., McIntyre, M., Neumann, M., Parra, M., Piccini, M., Rasay, R., RICKS, R., Schooley, A., Stackpole, E., Timucin, L., Yost, B., Young, A. 2014; 93: 501-508
  • Biological System Development for GraviSat: A New Platform for Studying Photosynthesis and Microalgae in Space Life Sciences in Space Research Fleming, E. M., Bebout, B. M., Tan, M. X., Selch, F., Ricco, A. J. 2014; 3: 63-75
  • Individual Platelet Adhesion Assay: Measuring Platelet Function and Antiplatelet Therapies in Whole Blood via Digital Quantification of Cell Adhesion ANALYTICAL CHEMISTRY Lopez-Alonso, A., Jose, B., Somers, M., Egan, K., Foley, D. P., Ricco, A. J., Ramstrom, S., Basabe-Desmonts, L., Kenny, D. 2013; 85 (13): 6497-6504

    Abstract

    Widespread monitoring of platelet function and the effect of antiplatelet drugs will improve outcomes in cardiovascular patients, but platelet function testing is not routine in clinical practice. We report a rapid, accurate methodology to quantify platelet-protein interactions: a microarray of contact-printed 6-μm fibrinogen dots on a transparent substrate binds platelets from whole blood, one platelet per dot. The fractional occupancy of an array of fibrinogen dots after a predefined incubation time quantitatively assays platelet adhesion to the protein matrix. We demonstrate this technique by measurement of platelet adhesion to fibrinogen as a means to quantify the effect of the P2Y12 and αIIbβ3 receptor inhibitors cangrelor and abciximab, respectively, both in vitro--by incubating the drug with a freshly drawn blood sample--and in blood from patients treated with antiplatelet agents. The effects of single- and dual-antiplatelet therapy are also assessed. Results from this platelet-binding assay are well correlated with standard techniques including flow cytometry and light transmission aggregometry. This assay technology, readily integrated with microfluidic platforms, is generally applicable to the assay of cell-protein interactions and promises more effective, rapid assay of drug effects in cardiovascular disease patients.

    View details for DOI 10.1021/ac401076s

    View details for Web of Science ID 000321521700050

    View details for PubMedID 23713824

  • Assaying the efficacy of dual-antiplatelet therapy: use of a controlled-shear-rate microfluidic device with a well-defined collagen surface to track dynamic platelet adhesion ANALYTICAL AND BIOANALYTICAL CHEMISTRY Lucitt, M. B., O'Brien, S., Cowman, J., Meade, G., Basabe-Desmonts, L., Somers, M., Kent, N., Ricco, A. J., Kenny, D. 2013; 405 (14): 4823-4834

    Abstract

    We report the development and demonstration of an assay that distinguishes the pharmacological effects of two widely used antiplatelet therapies, aspirin (COX-1 inhibitor) and clopidogrel (P2Y12 inhibitor). Whole blood is perfused through a low-volume microfluidic device in contact with a well-characterized (ellipsometry, atomic force microscopy) acid-soluble type I collagen surface. Whole human blood treated in vitro with a P2Y12 inhibitor 2-methylthioadenosine 5'-monophosphate triethylammonium salt (2-MeSAMP) extended the time to the start of platelet recruitment, i.e., platelet binding to the collagen surface. Treatment with 2-MeSAMP also slowed the rate of aggregate buildup, with an overall reduced average platelet aggregate area after 8 min of constant blood flow. A far smaller effect was observed for in vitro treatment with aspirin, for which the rate of change of surface coverage is indistinguishable from controls. In whole blood obtained from patients under treatment with dual-antiplatelet therapy (aspirin and clopidogrel), a significant extension of time to platelet recruitment was observed along with a slowed rate of aggregate buildup and an average aggregate size approximately half that of control measurements. Differentiation of the pharmacological effects of these two well-targeted antiplatelet pathways suggests a role for this assay in determining the antiplatelet effects of these and related new therapeutics in clinical settings.

    View details for DOI 10.1007/s00216-013-6897-y

    View details for Web of Science ID 000318312400015

    View details for PubMedID 23535745

  • Microfluidic impedance cytometer for platelet analysis LAB ON A CHIP Evander, M., Ricco, A. J., Morser, J., Kovacs, G. T., Leung, L. L., Giovangrandi, L. 2013; 13 (4): 722-729

    Abstract

    We present the design and performance characteristics of a platelet analysis platform based on a microfluidic impedance cytometer. Dielectrophoretic focusing is used to centre cells in a fluid stream, which then forms the core of a two-phase flow (dielectric focusing). This flow then passes between electrodes for analysis by differential impedance spectroscopy at multiple frequencies from 280 kHz to 4 MHz. This approach increases the signal-to-noise ratio relative to a single-phase, unfocused stream, while minimising the shear forces to which the cells are subjected. The percentage of activated platelets before and after passage through the chip was measured using flow cytometry, and no significant change was measured. Measuring the in-phase amplitude at a single frequency is sufficient to distinguish platelets from erythrocytes. Using multi-frequency impedance measurements and discriminant analysis, resting platelets can be discriminated from activated platelets. This multifrequency impedance cytometer therefore allows ready determination of the degree of platelet activation in blood samples.

    View details for DOI 10.1039/c2lc40896a

    View details for Web of Science ID 000313971300028

    View details for PubMedID 23282651

  • CubeSats as Innovative Science Platforms JOURNAL OF SMALL SATELLITES Ehrenfreund, P., Quinn, R. C., Ricco, A. J. 2013; 2 (1): 79-81
  • Reactive deposition of nano-films in deep polymeric microcavities LAB ON A CHIP Riaz, A., Gandhiraman, R. P., Dimov, I. K., Basabe-Desmonts, L., Ducree, J., Daniels, S., Ricco, A. J., Lee, L. P. 2012; 12 (22): 4877-4883

    Abstract

    We report the controlled diffusion of gas-phase high-reactivity chemical species into long polymeric microcavities to form glass-like, low-permeability barrier films on the interior surfaces of the microcavities. Reactive species created from fragmentation of O(2) and hexamethyldisiloxane (HMDSO) in a radio-frequency (RF) plasma environment are allowed to diffuse into the microcavities of polydimethylsiloxane (PDMS), where surface reactions lead to the formation of an effective, glass-like thin-film barrier. Reactive species including silicon radicals and elemental oxygen maintain their reactivity for sufficient times (up to 7000 s) and survive the random diffusional walk through the microcavities to form glass barriers as much as 65 mm from the cavity entrance. The barrier thickness and the growth length can be controlled by the reaction time and chamber operating pressure. Increasing the cross sectional area of the cavity inlet and/or decreasing the mean free path was found to increase the thickness of the barrier film. Optical emission spectroscopic analysis was used to characterize the reactive fragments formed from HMDSO, and energy-dispersive X-ray analysis revealed that the barrier composition is consistent with oxides of silicon (SiO(x)). Formed inside PDMS microcavities, the glass barrier blocks the penetration or absorption of small molecules such as rhodamine B (RhB) and biotin, and also resists permeation of organic solvents such as toluene, preventing the PDMS microfluidic structures from swelling and deforming. Moreover, formation of glass-like thin films in PDMS microcavities enhances the stability of electroosmotic flow (EOF) relative to uncoated PDMS devices, in which EOF instabilities are significant; this enables separation by electrophoresis with reproducibility (relative standard deviation 3%, n = 5) and baseline peak resolution (R:1.3) comparable to that obtained in conventional fused-silica capillaries.

    View details for DOI 10.1039/c2lc40296c

    View details for Web of Science ID 000310865200038

    View details for PubMedID 23032697

  • The O/OREOS Mission: First Science Data from the Space Environment Viability of Organics (SEVO) Payload ASTROBIOLOGY Mattioda, A., Cook, A., Ehrenfreund, P., Quinn, R., Ricco, A. J., Squires, D., Bramall, N., Bryson, K., Chittenden, J., Minelli, G., Agasid, E., Allamandola, L., Beasley, C., Burton, R., Defouw, G., Diaz-Aguado, M., Fonda, M., Friedericks, C., Kitts, C., Landis, D., Mclntyre, M., Neumann, M., Rasay, M., Ricks, R., Salama, F., Santos, O., Schooley, A., Yost, B., Young, A. 2012; 12 (9): 841-853

    Abstract

    We report the first science results from the Space Environment Viability of Organics (SEVO) payload aboard the Organism/Organic Exposure to Orbital Stresses (O/OREOS) free-flying nanosatellite, which completed its nominal spaceflight mission in May 2011 but continues to acquire data biweekly. The SEVO payload integrates a compact UV-visible-NIR spectrometer, utilizing the Sun as its light source, with a 24-cell sample carousel that houses four classes of vacuum-deposited organic thin films: polycyclic aromatic hydrocarbon (PAH), amino acid, metalloporphyrin, and quinone. The organic films are enclosed in hermetically sealed sample cells that contain one of four astrobiologically relevant microenvironments. Results are reported in this paper for the first 309 days of the mission, during which the samples were exposed for ∼2210 h to direct solar illumination (∼1080 kJ/cm(2) of solar energy over the 124-2600 nm range). Transmission spectra (200-1000 nm) were recorded for each film, at first daily and subsequently every 15 days, along with a solar spectrum and the dark response of the detector array. Results presented here include eight preflight and 16 in-flight spectra of eight SEVO sample cells. Spectra from the PAH thin film in a water-vapor-containing microenvironment indicate measurable change due to solar irradiation in orbit, while three other nominally water-free microenvironments show no appreciable change. The quinone anthrarufin showed high photostability and no significant spectroscopically measurable change in any of the four microenvironments during the same period. The SEVO experiment provides the first in situ real-time analysis of the photostability of organic compounds and biomarkers in orbit.

    View details for DOI 10.1089/ast.2012.0861

    View details for Web of Science ID 000309055200004

    View details for PubMedID 22984872

  • Effective Hydrodynamic Shaping of Sample Streams in a Microfluidic Parallel-Plate Flow-Assay Device: Matching Whole Blood Dynamic Viscosity IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING O'Brien, S., Kent, N. J., Lucitt, M., Ricco, A. J., McAtamney, C., Kenny, D., Meade, G. 2012; 59 (2): 374-382

    Abstract

    We report the development of an aqueous buffer system tailored to the fluidic and hemodynamic requirements of our recently reported microfluidic platelet dynamic assay device, which uses hydrodynamic focusing to "shape" a blood sample into a thin flowing layer adjacent to its protein-functionalized surface. By matching the dynamic viscosity of whole blood (3.13 ± 0.08 mPa·s, from healthy donors), the selected buffer minimizes interfacial fluid mixing and better controls shear rate within the device, permitting platelet/protein-surface interaction assays with as little as 50 μL of whole blood. Buffers containing the viscosity-enhancing components bovine serum albumin (BSA), gelofusine/glycine, or histopaque (Ficoll gradient solution) were found not to activate platelets when incubated with blood at concentrations up to 50%, as assessed by flow cytometry quantitation of P-selectin expression and αIIbβ (3) activation. In contrast, glycerol-based buffer activated platelets (two-fold increase in P-selectin levels) at concentrations as low as 10% by volume. BSA- and gelofusine/glycine-based buffers were problematic in preparation and use, and therefore, were not used beyond initial characterization. The histopaque solution selected as the best choice for flow studies stabilizes sample contact with the device's thrombogenic surface, does not activate platelets, and does not interfere with the action of agonists added to deliberately activate platelets.

    View details for DOI 10.1109/TBME.2011.2172607

    View details for Web of Science ID 000300507800010

    View details for PubMedID 22020664

  • Point of Care Diagnostics: Status and Future ANALYTICAL CHEMISTRY Gubala, V., Harris, L. F., Ricco, A. J., Tan, M. X., Williams, D. E. 2012; 84 (2): 487-515

    View details for DOI 10.1021/ac2030199

    View details for Web of Science ID 000299134400002

    View details for PubMedID 22221172

  • The development of the Space Environment Viability of Organics (SEVO) experiment aboard the Organism/Organic Exposure to Orbital Stresses (O/OREOS) satellite PLANETARY AND SPACE SCIENCE Bramall, N. E., Quinn, R., Mattioda, A., Bryson, K., Chittenden, J. D., Cook, A., Taylor, C., Minelli, G., Ehrenfreund, P., Ricco, A. J., Squires, D., Santos, O., Friedericks, C., Landis, D., Jones, N. C., Salama, F., Allamandola, L. J., Hoffmann, S. V. 2012; 60 (1): 121-130
  • The ORGANIC experiment on EXPOSE-R on the ISS: Flight sample preparation and ground control spectroscopy ADVANCES IN SPACE RESEARCH Bryson, K. L., Peeters, Z., Salama, F., Foing, B., Ehrenfreund, P., Ricco, A. J., JESSBERGER, E., Bischoff, A., Breitfellner, M., Schmidt, W., Robert, F. 2011; 48 (12): 1980-1996
  • The O/OREOS Mission: First Science Data from the Space Environment Survivability of Living Organisms (SESLO) Payload ASTROBIOLOGY Nicholson, W. L., Ricco, A. J., Agasid, E., Beasley, C., Diaz-Aguado, M., Ehrenfreund, P., Friedericks, C., Ghassemieh, S., Henschke, M., Hines, J. W., Kitts, C., Luzzi, E., Ly, D., Mai, N., Mancinelli, R., McIntyre, M., Minelli, G., Neumann, M., Parra, M., Piccini, M., Rasay, R. M., Ricks, R., Santos, O., Schooley, A., Squires, D., Timucin, L., Yost, B., Young, A. 2011; 11 (10): 951-958

    Abstract

    We report the first telemetered spaceflight science results from the orbiting Space Environment Survivability of Living Organisms (SESLO) experiment, executed by one of the two 10 cm cube-format payloads aboard the 5.5 kg Organism/Organic Exposure to Orbital Stresses (O/OREOS) free-flying nanosatellite. The O/OREOS spacecraft was launched successfully to a 72° inclination, 650 km Earth orbit on 19 November 2010. This satellite provides access to the radiation environment of space in relatively weak regions of Earth's protective magnetosphere as it passes close to the north and south magnetic poles; the total dose rate is about 15 times that in the orbit of the International Space Station. The SESLO experiment measures the long-term survival, germination, and growth responses, including metabolic activity, of Bacillus subtilis spores exposed to the microgravity, ionizing radiation, and heavy-ion bombardment of its high-inclination orbit. Six microwells containing wild-type (168) and six more containing radiation-sensitive mutant (WN1087) strains of dried B. subtilis spores were rehydrated with nutrient medium after 14 days in space to allow the spores to germinate and grow. Similarly, the same distribution of organisms in a different set of microwells was rehydrated with nutrient medium after 97 days in space. The nutrient medium included the redox dye Alamar blue, which changes color in response to cellular metabolic activity. Three-color transmitted intensity measurements of all microwells were telemetered to Earth within days of each of the 48 h growth experiments. We report here on the evaluation and interpretation of these spaceflight data in comparison to delayed-synchronous laboratory ground control experiments.

    View details for DOI 10.1089/ast.2011.0714

    View details for Web of Science ID 000298345600002

    View details for PubMedID 22091486

  • Shear-Mediated Platelet Adhesion Analysis in Less Than 100 mu L of Blood: Toward a POC Platelet Diagnostic IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Kent, N. J., O'Brien, S., Basabe-Desmonts, L., Meade, G. R., MacCraith, B. D., Corcoran, B. G., Kenny, D., Ricco, A. J. 2011; 58 (3): 826-830

    Abstract

    We report a microfluidic chip-based hydrodynamic focusing approach that minimizes sample volume for the analysis of cell-surface interactions under controlled fluid-shear conditions. Assays of statistically meaningful numbers of translocating platelets interacting with immobilized von Willebrand factor at arterial shear rates (∼1500 s(-1)) are demonstrated. By controlling spatial disposition and relative flow rates of two contacting fluid streams, e.g., sample (blood) and aqueous buffer, on-chip hydrodynamic focusing guides the cell-containing stream across the protein surface as a thin fluid layer, consuming ∼50 μL of undiluted whole blood for a 2-min platelet assay. Control of wall shear stress is independent of sample consumption for a given flow time. The device design implements a mass-manufacturable fabrication approach. Fluorescent labeling of cells enables readout using standard microscopy tools. Customized image-analysis software rapidly quantifies cellular surface coverage and aggregate size distributions as a function of time during blood-flow analyses, facilitating assessment of drug treatment efficacy or diagnosis of disease state.

    View details for DOI 10.1109/TBME.2010.2090659

    View details for Web of Science ID 000287663100023

    View details for PubMedID 21342809

  • Cubesats: Cost-effective science and technology platforms for emerging and developing nations ADVANCES IN SPACE RESEARCH Woellert, K., Ehrenfreund, P., Ricco, A. J., Hertzfeld, H. 2011; 47 (4): 663-684
  • Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS) LAB ON A CHIP Dimov, I. K., Basabe-Desmonts, L., Garcia-Cordero, J. L., Ross, B. M., Ricco, A. J., Lee, L. P. 2011; 11 (5): 845-850

    Abstract

    We present a self-powered integrated microfluidic blood analysis system (SIMBAS) that does not require any external connections, tethers, or tubing to deliver and analyze a raw whole-blood sample. SIMBAS only requires the user to place a 5 μL droplet of whole-blood at the inlet port of the device, whereupon the stand-alone SIMBAS performs on-chip removal of red and white cells, without external valving or pumping mechanisms, followed by analyte detection in platelet-containing plasma. Five complete biotin-streptavidin sample-to-answer assays are performed in 10 min; the limit of detection is 1.5 pM. Red and white blood cells are removed by trapping them in an integral trench structure. Simulations and experimental data show 99.9% to 100% blood cell retention in the passive structure. Powered by pre-evacuation of its PDMS substrate, SIMBAS' guiding design principle is the integration of the minimal number of components without sacrificing effectiveness in performing rapid complete bioassays, a critical step towards point-of-care molecular diagnostics.

    View details for DOI 10.1039/c0lc00403k

    View details for Web of Science ID 000287409600010

    View details for PubMedID 21152509

  • Microfluidic device to study arterial shear-mediated platelet-surface interactions in whole blood: reduced sample volumes and well-characterised protein surfaces BIOMEDICAL MICRODEVICES Kent, N. J., Basabe-Desmonts, L., Meade, G., MacCraith, B. D., Corcoran, B. G., Kenny, D., Ricco, A. J. 2010; 12 (6): 987-1000

    Abstract

    We report a novel device to analyze cell-surface interactions under controlled fluid-shear conditions on well-characterised protein surfaces. Its performance is demonstrated by studying platelets interacting with immobilised von Willebrand Factor at arterial vascular shear rates using just 200 μL of whole human blood per assay. The device's parallel-plate flow chamber, with 0.1 mm² cross sectional area and height-to-width ratio of 1:40, provides uniform, well-defined shear rates along the chip surface with negligible vertical wall effects on the fluid flow profile while minimizing sample volumetric flow. A coating process was demonstrated by ellipsometry, atomic force microscopy, and fluorescent immunostaining to provide reproducible, homogeneous, uniform protein layers over the 0.7 cm² cell-surface interaction area. Customized image processing quantifies dynamic cellular surface coverage vs. time throughout the whole-blood-flow assay for a given drug treatment or disease state. This device can track the dose response of anti-platelet drugs, is suitable for point-of-care diagnostics, and is designed for adaptation to mass manufacture.

    View details for DOI 10.1007/s10544-010-9453-y

    View details for Web of Science ID 000283246500004

    View details for PubMedID 20652753

  • Microfluidic sedimentation cytometer for milk quality and bovine mastitis monitoring BIOMEDICAL MICRODEVICES Garcia-Cordero, J. L., Barrett, L. M., O'Kennedy, R., Ricco, A. J. 2010; 12 (6): 1051-1059

    Abstract

    We report a rapid, low-cost, portable microfluidic sedimentation cytometer (SeCy) for assessing the somatic cell count and fat content of milk in 15 min using a "sample-in, answer-out" approach. The system consists of 12 independent microfluidic devices, essentially flattened funnel structures, fabricated on the footprint of a single plastic compact disc (CD). Each funnel structure holds 150 μL of milk, has an inlet for milk filling and an outlet for air to escape, and ends in a narrow, closed-end microfluidic channel that facilitates packing of the cells into a column whose length is proportional to cell count. The closed-end channel provides accurate cell counts over the range 50,000->3,000,000 cells per mL. The assay separates cells and fat globules based on their densities (by differential sedimentation), concentrating white cells in the closed-end channel near the outer rim of the CD for estimation of total "cell pellet" volume, while fat globules move toward the center of disc rotation, forming a fat "band" in the funnel. After adding milk to two or more microfluidic devices, the CD is loaded onto a custom-built reader unit that spins the disc for 15 min. Two low-cost microscopes in the reader image the centrifuged cell pellet and the fat band, providing a sufficiently accurate cell count to diagnose mastitis and measuring fat content as an indication of health and nutritional status.

    View details for DOI 10.1007/s10544-010-9459-5

    View details for Web of Science ID 000283246500010

    View details for PubMedID 20680463

  • Detection of Water in the LCROSS Ejecta Plume SCIENCE Colaprete, A., Schultz, P., Heldmann, J., Wooden, D., Shirley, M., Ennico, K., Hermalyn, B., Marshall, W., Ricco, A., Elphic, R. C., Goldstein, D., Summy, D., Bart, G. D., Asphaug, E., Korycansky, D., Landis, D., Sollitt, L. 2010; 330 (6003): 463-468

    Abstract

    Several remote observations have indicated that water ice may be presented in permanently shadowed craters of the Moon. The Lunar Crater Observation and Sensing Satellite (LCROSS) mission was designed to provide direct evidence. On 9 October 2009, a spent Centaur rocket struck the persistently shadowed region within the lunar south pole crater Cabeus, ejecting debris, dust, and vapor. This material was observed by a second "shepherding" spacecraft, which carried nine instruments, including cameras, spectrometers, and a radiometer. Near-infrared absorbance attributed to water vapor and ice and ultraviolet emissions attributable to hydroxyl radicals support the presence of water in the debris. The maximum total water vapor and water ice within the instrument field of view was 155 ± 12 kilograms. Given the estimated total excavated mass of regolith that reached sunlight, and hence was observable, the concentration of water ice in the regolith at the LCROSS impact site is estimated to be 5.6 ± 2.9% by mass. In addition to water, spectral bands of a number of other volatile compounds were observed, including light hydrocarbons, sulfur-bearing species, and carbon dioxide.

    View details for DOI 10.1126/science.1186986

    View details for Web of Science ID 000283329100028

    View details for PubMedID 20966242

  • Integrated system investigating shear-mediated platelet interactions with von Willebrand factor using microliters of whole blood ANALYTICAL BIOCHEMISTRY Lincoln, B., Ricco, A. J., Kent, N. J., Basabe-Desmonts, L., Lee, L. P., MacCraith, B. D., Kenny, D., Meade, G. 2010; 405 (2): 174-183

    Abstract

    We report an integrated platelet translocation analysis system that measures complex dynamic platelet-protein surface interactions in microliter volumes of unmodified anticoagulated whole blood under controlled fluid shear conditions. The integrated system combines customized platelet-tracking image analysis with a custom-designed microfluidic parallel plate flow chamber and defined von Willebrand factor surfaces to assess platelet trajectories. Using a position-based probability function that accounts for image noise and preference for downstream movement, outputs include instantaneous and mean platelet velocities, periods of motion and stasis, and bond dissociation kinetics. Whole blood flow data from healthy donors at an arterial shear rate (1500 s(-1)) show mean platelet velocities from 8.9+/-1.0 to 12+/-4 microm s(-1). Platelets in blood treated with the antiplatelet agent c7E-Fab fragment spend more than twice as much time in motion as platelets from untreated control blood; the bond dissociation rate constant (k(off)) increases 1.3-fold, whereas mean translocation velocities do not differ. Blood from healthy unmedicated donors was used to assess flow assay reproducibility, donor variability, and the effects of antiplatelet treatment. This integrated system enables reliable, rapid populational quantification of platelet translocation under pathophysiological vascular fluid shear using as little as 150 microl of blood.

    View details for DOI 10.1016/j.ab.2010.05.030

    View details for Web of Science ID 000281296300005

    View details for PubMedID 20513436

  • Liquid recirculation in microfluidic channels by the interplay of capillary and centrifugal forces MICROFLUIDICS AND NANOFLUIDICS Garcia-Cordero, J. L., Basabe-Desmonts, L., Ducree, J., Ricco, A. J. 2010; 9 (4-5): 695-703
  • Single-Step Separation of Platelets from Whole Blood Coupled with Digital Quantification by Interfacial Platelet Cytometry (iPC) LANGMUIR Basabe-Desmonts, L., Ramstrom, S., Meade, G., O'Neill, S., Riaz, A., Lee, L. P., Ricco, A. J., Kenny, D. 2010; 26 (18): 14700-14706

    Abstract

    We report the efficient single-step separation of individual platelets from unprocessed whole blood, enabling digital quantification of platelet function using interfacial platelet cytometry (iPC) on a chip. iPC is accomplished by the precision micropatterning of platelet-specific protein surfaces on solid substrates. By separating platelets from whole blood using specific binding to protein spots of a defined size, iPC implements a simple incubate-and-rinse approach, without sample preparation, that enables (1) the study of platelets in the physiological situation of interaction with a protein surface, (2) the choice of the number of platelets bound on each protein spot, from one to many, (3) control of the platelet-platelet distance, including the possibility to study noninteracting single platelets, (4) digital quantification (counting) of platelet adhesion to selected protein matrices, enabling statistical characterization of platelet subpopulations from meaningfully large numbers of single platelets, (5) the study of platelet receptor expression and spatial distribution, and (6) a detailed study of the morphology of isolated single platelets at activation levels that can be manipulated. To date, we have demonstrated 1-4 of the above list. Platelets were separated from whole blood using iPC with fibrinogen, von Willebrand factor (VWF), and anti-CD42b antibody printed "spots" ranging from a fraction of one to several platelet diameters (2-24 μm). The number of platelets captured per spot depends strongly on the protein matrix and the surface area of the spot, together with the platelet volume, morphology, and activation state. Blood samples from healthy donors, a May-Hegglin-anomaly patient, and a Glanzmann's Thrombasthenia patient were analyzed via iPC to confirm the specificity of the interaction between protein matrices and platelets. For example, the results indicate that platelets interact with fibrinogen spots only through the fibrinogen receptor (αIIbβ3) and, relevant to diagnostic applications, platelet adhesion correlates strongly with normal versus abnormal platelet function. A critical function of platelets is to adhere to regions of damage on blood vessel walls; in contrast to conventional flow cytometry, where platelets are suspended in solution, iPC enables physiologically relevant platelet bioassays based on platelet/protein-matrix interactions on surfaces. This technology should be inexpensive to implement in clinical assay format, is readily integrable into fluidic microdevices, and paves the way for high-throughput platelet assays from microliter volumes of whole blood.

    View details for DOI 10.1021/la9039682

    View details for Web of Science ID 000281690600047

    View details for PubMedID 20108942

  • Optically addressable single-use microfluidic valves by laser printer lithography LAB ON A CHIP Garcia-Cordero, J. L., Kurzbuch, D., Benito-Lopez, F., Diamond, D., Lee, L. P., Ricco, A. J. 2010; 10 (20): 2680-2687

    Abstract

    We report the design, fabrication, and characterization of practical microfluidic valves fabricated using laser printer lithography. These optofluidic valves are opened by directing optical energy from a solid-state laser, with similar power characteristics to those used in CD/DVD drives, to a spot of printed toner where localized heating melts an orifice in the polymer layer in as little as 500 ms, connecting previously isolated fluidic components or compartments. Valve functionality, response time, and laser input energy dependence of orifice size are reported for cyclo-olefin polymer (COP) and polyethylene terephthalate (PET) films. Implementation of these optofluidic valves is demonstrated on pressure-driven and centrifugal microfluidic platforms. In addition, these "one-shot" valves comprise a continuous polymer film that hermetically isolates on-chip fluid volumes within fluidic devices using low-vapor-permeability materials; we confirmed this for a period of one month. The fabrication and integration of optofluidic valves are compatible with a range of polymer microfabrication technologies and should facilitate the development of fully integrated, reconfigurable, and automated lab-on-a-chip systems, particularly when reagents must be stored on chip for extended periods, e.g. for medical diagnostic devices, lab-on-a-chip synthetic systems, or hazardous biochemical analysis platforms.

    View details for DOI 10.1039/c004980h

    View details for Web of Science ID 000282314200006

    View details for PubMedID 20740236

  • Evolving Point-of-Care Diagnostics Using Up-Converting Phosphor Bioanalytical Systems ANALYTICAL CHEMISTRY Ouellette, A. L., Li, J. J., Cooper, D. E., Ricco, A. J., Kovacs, G. T. 2009; 81 (9): 3216-3221

    Abstract

    Up-converting phosphors promise simpler readout systems with less background at a given signal level than many other popular approaches. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs.acs.org/journal/ancham.).

    View details for DOI 10.1021/ac900475u

    View details for Web of Science ID 000265632400007

    View details for PubMedID 19368339

  • Optical scanner for immunoassays with up-converting phosphorescent labels IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Li, J. J., Ouellette, A. L., Giovangrandi, L., Cooper, D. E., Ricco, A. J., Kovacs, G. T. 2008; 55 (5): 1560-1571

    Abstract

    A 2-D optical scanner was developed for the imaging and quantification of up-converting phosphor (UCP) labels in immunoassays. With resolution better than 500 microm, a scan rate of 0.4 mm/s, and a 1-2% coefficient of variation for repeatability, this scanner achieved a detection limit of fewer than 100 UCP particles in an 8.8. x 10(4) microm(2) area and a dynamic range that covered more than three orders of magnitude. Utilizing this scanner, a microfluidic chip immunoassay for the cytokine interferon-gamma (IFN-gamma) was developed: concentrations as low as 3 pM (50 pg/mL) were detected from 100 microL samples with a total assay time of under an hour, including the 8 min readout. For this UCP-based assay, 2-D images of the capture antibody lines were scanned, image processing techniques were employed to extract the UCP emission signals, a response curve that spanned 3-600 pM IFN-gamma was generated, and a five-parameter logistic mathematical model was fitted to the data for determination of unknown IFN-gamma concentrations. Relative to common single-point or 1-D scanning optical measurements, our results suggest that a simple 2-D imaging system can speed assay development, reduce errors, and improve accuracy by characterizing the spatial distribution and uniformity of surface-captured optical labels as a function of assay conditions and device parameters.

    View details for DOI 10.1109/TBME.2007.914674

    View details for Web of Science ID 000255148600011

    View details for PubMedID 18440902

  • Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics LAB ON A CHIP Dimov, I. K., Garcia-Cordero, J. L., O'Grady, J., Poulsen, C. R., Viguier, C., Kent, L., Daly, P., Lincoln, B., Maher, M., O'Kennedy, R., Smith, T. J., Ricco, A. J., Lee, L. P. 2008; 8 (12): 2071–78

    Abstract

    We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process.

    View details for DOI 10.1039/b812515e

    View details for Web of Science ID 000261686200012

    View details for PubMedID 19023470

  • Autonomous genetic analysis system to study space effects on microorganisms: Results from orbit 14th International Conference on Solid-State Sensors, Actuators and Microsystems/21st European Conference on Solid-State Transducers Ricco, A. J., Hines, J. W., Piccini, M., Parra, M., Timucin, L., Barker, V., Storment, C., Friedericks, C., Agasid, E., Beasley, C., Giovangrandi, L., Henschke, M., Kitts, C., Levine, L., Luzzi, E., Ly, D., Mas, I., McIntyre, M., Oswell, D., Rasay, R., RICKS, R., Ronzano, K., Squires, D., Swaiss, G., Tucker, J., Yost, B. IEEE. 2007
  • Integrating polymerase chain reaction, valving, and electrophoresis in a plastic device for bacterial detection ANALYTICAL CHEMISTRY Koh, C. G., Tan, W., Zhao, M. Q., Ricco, A. J., Fan, Z. H. 2003; 75 (17): 4591–98

    Abstract

    An integrated plastic microfluidic device was designed and fabricated for bacterial detection and identification. The device, made from poly(cyclic olefin) with integrated graphite ink electrodes and photopatterned gel domains, accomplishes DNA amplification, microfluidic valving, sample injection, on-column labeling, and separation. Polymerase chain reaction (PCR) is conducted in a channel reactor containing a volume as small as 29 nL; thermal cycling utilizes screen-printed graphite ink resistors. In situ gel polymerization was employed to form local microfluidic valves that minimize convective flow of the PCR mixture into other regions. After PCR, amplicons (products) are electrokinetically injected through the gel valve, followed by on-chip electrophoretic separation. An intercalating dye is admixed to label the amplicons; they are detected using laser-induced fluorescence. Two model bacteria, Escherichia coli O157 and Salmonella typhimurium, were chosen to demonstrate bacterial detection and identification based on amplification of several of their unique DNA sequences. The limit of detection is about six copies of target DNA.

    View details for DOI 10.1021/ac0343836

    View details for Web of Science ID 000185192300042

    View details for PubMedID 14632069

  • Use of floating electrodes in transient isotachophoresis to increase the sensitivity of detection LAB ON A CHIP Kurnik, R. T., Boone, T. D., Nguyen, U., Ricco, A. J., Williams, S. J. 2003; 3 (2): 86–92

    Abstract

    We report a protocol for on-chip electrophoretic sample loading and sample component separation in which each operation requires simultaneous control of the potential of only two electrodes: during the sample-loading phase, the potentials at the ends of the separation channel are electrically floating; during electrophoresis of the sample mixture down the separation channel, the potentials at the ends of the sample-introduction channel are floating. This method, which we call "floating-stacking," avoids the dispersion/distortion of the sample plug that is commonly associated with simultaneous electrical control of only two electrodes in a crossed-channel or offset-double-tee injection system. Further, when this floating loading/separation is done in the presence of back-transient-isotachophoresis, sample loss from the plug of material being injected is minimal and a significant concentration increase--up to 13x--of the sample components in the separated bands occurs relative to the commonly used "pinch-and-pull-back" technique (which requires simultaneous electrical control of four electrodes).

    View details for DOI 10.1039/b212729f

    View details for Web of Science ID 000182988000011

    View details for PubMedID 15100788

  • Mars Atmospheric Oxidant Sensor (MAOS): an In-Situ Heterogeneous Chemistry Analysis PLANETARY AND SPACE SCIENCE Zent, A. P., Quinn, R. C., Grunthaner, F. C., Hecht, M. H., Buehler, M. G., McKay, C. P., Ricco, A. J. 2003; 51 (3): 167-175
  • Miniaturized capillary isoelectric focusing in plastic microfluidic devices ELECTROPHORESIS Tan, W., Fan, Z. H., Qiu, C. X., Ricco, A. J., Gibbons 2002; 23 (20): 3638–45

    Abstract

    We report the demonstration of miniaturized capillary isoelectric focusing (CIEF) in plastic microfluidic devices. Conventional CIEF technique was adapted to the microfluidic devices to separate proteins and to detect protein-protein interactions. Both acidic and basic proteins with isoelectric points (pI) ranging from 5.4 to 11.0 were rapidly focused, mobilized, and detected in a 1.2 cm long channel (50 microm deep x 120 microm wide) with a total analysis time of 150 s. In a device with a focusing distance of 4.7 cm, the separation efficiency for a basic protein, lysozyme, was achieved as high as 1.5 x 10(5) plates, corresponding to 3.2 million plates per meter. We also experimentally confirmed that IEF resolution is essentially independent of focusing length when the applied voltage is kept the same and within a range that it does not cause Joule heating. Further, we demonstrated the use of miniaturized CIEF to study the interactions between two pairs of proteins, immunoglobulin G (IgG) with protein G and anti-six histidine (anti-6xHis) with 6xHis-tagged green fluorescent protein (GFP). Using this approach, protein-protein interactions can be detected for as little as 50 fmol of protein. We believe miniaturized CIEF is useful for studying protein-protein interactions when there is a difference in pI between a protein-protein complex and its constitutent proteins.

    View details for DOI 10.1002/1522-2683(200210)23:20<3638::AID-ELPS3638>3.0.CO;2-Y

    View details for Web of Science ID 000179159400024

    View details for PubMedID 12412135

  • Plastic advances microfluidic devices. ANALYTICAL CHEMISTRY Boone, T., Fan, Z. H., Hooper, H., Ricco, A., Tan, H. D., Williams, S. 2002; 74 (3): 78A–86A

    View details for DOI 10.1021/ac021943c

    View details for Web of Science ID 000173668200015

    View details for PubMedID 11838703

  • Use of linear salvation energy relationships for modeling responses from polymer-coated acoustic-wave vapor sensors ANALYTICAL CHEMISTRY Hierlemann, A., Zellers, E. T., Ricco, A. J. 2001; 73 (14): 3458–66

    Abstract

    The applicability and performance of linear solvation energy relationships (LSERs) as models of responses from polymer-coated acoustic-wave vapor sensors are critically examined. Criteria for the use of these thermodynamic models with thickness-shear-mode resonator (TSMR) and surface-acoustic-wave (SAW) vapor sensors are clarified. Published partition coefficient values derived from gas-liquid chromatography (GLC) are found to be consistently lower than those obtained gravimetrically, in accordance with previous reports, suggesting that LSERs based on GLC-derived partition coefficients will not provide accurate estimates of acoustic-wave sensor responses. The development of LSER models directly from polymer-coated TSMR vapor sensor response data is demonstrated and a revised model developed from SAW vapor sensor response data, which takes account of viscoelastic changes in polymeric coating films, is presented and compared to those developed by other methods.

    View details for DOI 10.1021/ac010083h

    View details for Web of Science ID 000169880300033

    View details for PubMedID 11476248

  • Conferring selectivity to chemical sensors via polymer side-chain selection: Thermodynamics of vapor sorption by a set of polysiloxanes on thickness-shear mode resonators ANALYTICAL CHEMISTRY Hierlemann, A., Ricco, A. J., Bodenhofer, K., Dominik, A., Gopel, W. 2000; 72 (16): 3696–3708

    Abstract

    Entropy of mixing is shown to be the driving interaction for the endothermic physisorption process of organic vapor partitioning into seven systematically side-chain-modified (polar, acidic, basic, polarizable side groups and groups interacting via H-bridges) polysiloxanes on thickness-shear mode resonators. Each sensor was exposed to seven analytes, selected for their diversity of functional groups. This systematic investigation of sorption yields benchmarking data on physisorption selectivity: response data and modeling reveal a direct correlation of partition coefficients with interactions between specific polymer side chains and analyte functional groups. Partition coefficients were determined for every polymer/analyte pairing over the 273-343 K range at 10 K intervals; from partition coefficient temperature dependence, overall absorption enthalpies and entropies were calculated. By subtracting the enthalpy and entropy of condensation for a given pure analyte, its mixing entropy (primarily combinatorial) and mixing enthalpy (associated with intermolecular interactions) with each polymer matrix were determined. These two crucial thermodynamic parameters determine the chemical selectivity patterns of the polymers for the analytes. Simple molecular modeling based on the polymer contact surface share of the modified side group or the introduced functional group reveals a direct correlation between the partition coefficients and the side-group variation.

    View details for DOI 10.1021/ac991298i

    View details for Web of Science ID 000088709200003

    View details for PubMedID 10959952

  • Differentiation of chemical components in a binary solvent vapor mixture using carbon/polymer composite-based chemiresistors ANALYTICAL CHEMISTRY Patel, S. V., Jenkins, M. W., Hughes, R. C., Yelton, W. G., Ricco, A. J. 2000; 72 (7): 1532–42

    Abstract

    We demonstrate a "universal solvent sensor" constructed from a small array of carbon/polymer composite chemiresistors that respond to solvents spanning a wide range of Hildebrand solubility parameters. Conductive carbon particles provide electrical continuity in these composite films. When the polymer matrix absorbs solvent vapors, the composite film swells, the average separation between carbon particles increases, and an increase in film resistance results, as some of the conduction pathways are broken. The adverse effects of contact resistance at high solvent concentrations are reported. Solvent vapors including isooctane, ethanol, diisopropylmethylphosphonate (DIMP), and water are correctly identified ("classified") using three chemiresistors, their composite coatings chosen to span the full range of solubility parameters. With the same three sensors, binary mixtures of solvent vapor and water vapor are correctly classified; following classification, two sensors suffice to determine the concentrations of both vapor components. Poly(ethylenevinyl acetate) and poly(vinyl alcohol) (PVA) are two such polymers that are used to classify binary mixtures of DIMP with water vapor; the PVA/carbon particle composite films are sensitive to less than 0.25% relative humidity. The Sandia-developed visual-empirical region of influence (VERI) technique is used as a method of pattern recognition to classify the solvents and mixtures and to distinguish them from water vapor. In many cases, the response of a given composite sensing film to a binary mixture deviates significantly from the sum of the responses to the isolated vapor components at the same concentrations. While these nonlinearities pose significant difficulty for (primarily) linear methods such as principal component analysis, VERI handles both linear and nonlinear data with equal ease. In the present study, the maximum speciation accuracy is achieved by an array containing three or four sensor elements, with the addition of more sensors resulting in a measurable accuracy decrease.

    View details for DOI 10.1021/ac990830z

    View details for Web of Science ID 000086225500032

    View details for PubMedID 10763250

  • Characteristics of acoustic plate modes on rotated Y-cuts of quarts utilised for biosensing applications ANALYTICAL CHEMISTRY Bender, F., Dahint, R., Josse, F., Ricco, A. J., Martin, S. J. 1999; 71 (22): 5064–68

    Abstract

    Acoustic plate modes (APM) on various quartz substrates have been investigated in order to determine their usefulness for liquid-sensing applications. The modes have been characterized in terms of their mass sensitivity, mode separation, temperature sensitivity, and reproducibility of the experimental results. Promising characteristics are found for rotated Y-cuts of quartz with the direction of acoustic mode propagation being perpendicular to the X-axis of the quartz crystal. Experiments on the detection of immunochemical reactions are performed using different quartz APM sensors, and the results are compared to similar experiments utilizing APM devices on ZX-LiNbO3.

    View details for DOI 10.1021/ac990559l

    View details for Web of Science ID 000083647100009

    View details for PubMedID 10575962

  • Application of the solubility parameter concept to the design of chemiresistor arrays JOURNAL OF THE ELECTROCHEMICAL SOCIETY Eastman, M. P., Hughes, R. C., Yelton, G., Ricco, A. J., Patel, S. V., Jenkins, M. W. 1999; 146 (10): 3907–13

    View details for DOI 10.1149/1.1392571

    View details for Web of Science ID 000083126400061

  • Reflectance infrared spectroscopy on operating surface acoustic wave chemical sensors during exposure to gas-phase analytes ANALYTICAL CHEMISTRY Thomas, R. C., Hierlemann, A., Staton, A. W., Hill, M., Ricco, A. J. 1999; 71 (16): 3615–21

    View details for DOI 10.1021/ac981447h

    View details for Web of Science ID 000082075100044

  • Effective use of molecular recognition in gas sensing: Results from acoustic wave and in situ FT-IR measurements ANALYTICAL CHEMISTRY Hierlemann, A., Ricco, A. J., Bodenhofer, K., Gopel, W. 1999; 71 (15): 3022–35

    Abstract

    To probe directly the analyte/film interactions that characterize molecular recognition in gas sensors, we recorded changes to the in situ surface vibrational spectra of specifically functionalized surface acoustic wave (SAW) devices concurrently with analyte exposure and SAW measurement of the extent of sorption. Fourier transform infrared external-reflectance spectra (FT-IR-ERS) were collected from operating 97-MHz SAW delay lines during exposure to a range of analytes as they interacted with thin-film coatings previously shown to be selective: cyclodextrins for chiral recognition, nickel camphorates for Lewis bases such as pyridine or organophosphonates, and phthalocyanines for aromatic compounds. In most cases where specific chemical interactions--metal coordination, "cage" compound inclusion, or pi-stacking--were expected, analyte dosing caused distinctive changes in the IR spectra, together with anomalously large SAW sensor responses. In contrast, control experiments involving the physisorption of the same analytes by conventional organic polymers did not cause similar changes in the IR spectra, and the SAW responses were smaller. For a given conventional polymer, the partition coefficients (or SAW sensor signals) roughly followed the analyte fraction of saturation vapor pressure. These SAW/FT-IR results support earlier conclusions derived from thickness-shear mode resonator data.

    View details for DOI 10.1021/ac981311j

    View details for Web of Science ID 000081877100025

    View details for PubMedID 10450152

  • Structural distortion of dendrimers on gold surfaces: A tapping-mode AFM investigation JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Hierlemann, A., Campbell, J. K., Baker, L. A., Crooks, R. M., Ricco, A. J. 1998; 120 (21): 5323–24

    View details for DOI 10.1021/ja974283f

    View details for Web of Science ID 000074039100026

  • SAW sensors for the room-temperature measurement of CO2 and relative humidity ANALYTICAL CHEMISTRY Hoyt, A. E., Ricco, A. J., Bartholomew, J. W., Osbourn, G. C. 1998; 70 (10): 2137–45

    View details for DOI 10.1021/ac971095z

    View details for Web of Science ID 000073666700019

  • Surface acoustic wave chemical sensor arrays: New chemically sensitive interfaces combined with novel cluster analysis to detect volatile organic compounds and mixtures ACCOUNTS OF CHEMICAL RESEARCH Ricco, A. J., Crooks, R. M., Osbourn, G. C. 1998; 31 (5): 289–96

    View details for DOI 10.1021/ar9600749

    View details for Web of Science ID 000073776300012

  • New organic materials suitable for use in chemical sensor arrays ACCOUNTS OF CHEMICAL RESEARCH Crooks, R. M., Ricco, A. J. 1998; 31 (5): 219–27

    View details for DOI 10.1021/ar970246h

    View details for Web of Science ID 000073776300005

  • Visual-empirical region-of-influence pattern recognition applied to chemical microsensor array selection and chemical analysis ACCOUNTS OF CHEMICAL RESEARCH Osbourn, G. C., Bartholomew, J. W., Ricco, A. J., Frye, G. C. 1998; 31 (5): 297–305

    View details for DOI 10.1021/ar970070j

    View details for Web of Science ID 000073776300013

  • The Mars Oxidant Experiment (MOx) for Mars '96 PLANETARY AND SPACE SCIENCE McKay, C. P., Grunthaner, F. J., Lane, A. L., Herring, M., Bartman, R. K., Ksendzov, A., Manning, C. M., Lamb, J. L., Williams, R. M., Ricco, A. J., Butler, M. A., Murray, B. C., Quinn, R. C., Zent, A. P., Klein, H. P., Levin, G. V. 1998; 46 (6-7): 769-777
  • Synthetic infrared spectra OPTICS LETTERS Sinclair, M. B., Butler, M. A., Kravitz, S. H., Zubrzycki, W. J., Ricco, A. J. 1997; 22 (13): 1036–38

    Abstract

    We have designed, microfabricated, and characterized a diffractive optical element that reproduces the infrared spectrum of HF from 3600 to 4300 cm(-1) . The reflection-mode diffractive optic consists of 4096 lines, each 4.5mum wide, at 16 discrete depths relative to the substrate from 0 to 1.2 mum and was fabricated upon a silicon wafer by anisotropic reactive ion-beam etching in a four-mask-level process. We envisage the use of diffractive optical elements of this type as the basis for a new class of miniaturized, remote chemical sensor systems based on correlation spectroscopy.

    View details for DOI 10.1364/OL.22.001036

    View details for Web of Science ID A1997XG25300032

    View details for PubMedID 18185744

  • Synthetic spectra: A tool for correlation spectroscopy APPLIED OPTICS Sinclair, M. B., Butler, M. A., Ricco, A. J., Senturia, S. D. 1997; 36 (15): 3342–48

    Abstract

    We show that computer-generated diffractive optical elements can be used to synthesize the infrared spectra of important compounds, and we describe a modified phase-retrieval algorithm useful for the design of elements of this type. In particular, we present the results of calculations of diffractive elements that are capable of synthesizing portions of the infrared spectra of gaseous hydrogen fluoride (HF) and trichloroethylene (TCE). Further, we propose a new type of correlation spectrometer that uses these diffractive elements rather than reference cells for the production of reference spectra. Storage of a large number of diffractive elements, each producing a synthetic spectrum corresponding to a different target compound, in compact-disk-like format will allow a spectrometer of this type to rapidly determine the composition of unknown samples. Other advantages of the proposed correlation spectrometer are also discussed.

    View details for DOI 10.1364/AO.36.003342

    View details for Web of Science ID A1997WZ08000024

    View details for PubMedID 18253347

  • Single-monolayer in situ modulus measurements using a SAW device - Photocrosslinking of a diacetylenic thiol-based monolayer Ricco, A. J., Staton, A. W., Crooks, R. M., Kim, T. ROYAL SOC CHEMISTRY. 1997: 247–58

    View details for DOI 10.1039/a704232i

    View details for Web of Science ID 000072767200016

  • Interactions between self-assembled monolayers and an organophosphonate - Detailed study using surface acoustic wave-based mass analysis, polarization modulation FTIR spectroscopy and ellipsometry Crooks, R. M., Yang, H. C., McEllistrem, L. J., Thomas, R. C., Ricco, A. J. ROYAL SOC CHEMISTRY. 1997: 285–305

    View details for DOI 10.1039/a704586g

    View details for Web of Science ID 000072767200018

  • Interactions between organized, surface-confined monolayers and vapor-phase probe molecules .9. Structure/reactivity relationship between three surface-confined isomers of mercaptobenzoic acid and vapor-phase decylamine LANGMUIR Wells, M., Dermody, D. L., Yang, H. C., Kim, T., Crooks, R. M., Ricco, A. J. 1996; 12 (8): 1989–96

    View details for DOI 10.1021/la9507951

    View details for Web of Science ID A1996UF82200009

  • Molecular interactions between organized, surface-confined monolayers and vapor-phase probe molecules .8. Reactions between acid-terminated self-assembled monolayers and vapor-phase bases LANGMUIR Yang, H. C., Dermody, D. L., Xu, C. J., Ricco, A. J., Crooks, R. M. 1996; 12 (3): 726–35

    View details for DOI 10.1021/la9505226

    View details for Web of Science ID A1996TV46600016