The Phillips Group

Detection and Signal Amplification


A primary area of focus is the design and synthesis of thermally-stable reagents that are capable of detecting specific chemical signals and then amplifying a response to that signal. Few reagents are capable of this type of dual response, and even fewer are thermally stable. Reagents that provide these capabilities will be useful in many applications ranging from diagnostic assays to stimuli-responsive materials.

Our research incorporates three interconnected areas of investigation that all benefit from our new reagents, polymers, and strategies for signal and target amplification.

Examples of our recent publications in this area:

  1. "A Thermally-Stable Enzyme Detection Assay that Amplifies Signal Autonomously in Water Without Assistance from Biological Reagents", Yeung, K.; Schmid, K. M.; Phillips, S. T.*, Chem. Commun., 2013, 49, 394–396.

  2. "Phase Switching to Enable Highly Selective Activity-Based Assays", Mohapatra, H.; Phillips, S. T.*, Anal. Chem., 2012, 84, 8927–8931.

  3. "Using Smell to Triage Samples in Point-of-Care Assays", Mohapatra, H.; Phillips, S. T.*, Angew. Chem. Int. Ed., 2012, 51, 11145–11148.

  4. "A Small Molecule Sensor for Fluoride Based on an Autoinductive, Colorimetric Signal Amplification Reaction", Baker, M. S.; Phillips, S. T.*, Org. Biomol. Chem., 2012, 10, 3595–3599.

  5. "Design of small molecule reagents that enable signal amplification via an autocatalytic, base-mediated cascade elimination reaction", Mohapatra, H.; Schmid, K. M.; Phillips, S. T.*, Chem. Commun. 2012, 48, 3018–3020.

  6. "A Structurally Simple Self-Immolative Reagent That Provides Three Distinct, Simultaneous Responses per Detection Event", Nuñez, S. A.; Yeung, K.; Fox, N. S.; Phillips, S. T.*, J. Org. Chem., 2011, 76, 10099–10113.

  7. "A Two-Component Small Molecule System for Activity-Based Detection and Signal Amplification: Application to the Visual Detection of Threshold Levels of Pd(II)", Baker, M.S.; Phillips, S. T.*, J. Am. Chem. Soc. 2011, 133, 5170–5173.

  8. "Use of Catalytic Fluoride under Neutral Conditions for Cleaving Silicon-Oxygen Bonds", DiLauro, A.; Seo, W.; Phillips, S. T.*, J. Org. Chem. 2011, 76, 7352–7358.

Point-of-Care Diagnostics


Low-cost diagnostics are urgently needed for diagnosing disease and detecting pollution in resource-limited settings. In addition to being both sensitive and selective, such diagnostics must be thermally stable, inexpensive, and easy to use. Standard antibodies, enzymes, nucleic acids, and silver(I) salts are too thermally unstable for use in extremely resource-limited environments (such as remote villages), and batteries and electronics are too expensive. Consequently, we view this problem as a unique opportunity to transform analytical chemistry for point-of-care diagnostics by developing entirely new types of assays, reagents, and assay platforms that enable highly sensitive and selective assays, yet overcome the difficult issues associated with conducting assays in resource-limited environments.

Video of a paper-based microfluidic timer for use with time based assays (16x speed)

Three-dimensional representation of analog dial device. The video shows the assembly of the device and then the response of the device after the addition of sample containing analyte. Representative results are shown for samples containing 30, 50 and 80 mM H2O2. The video shows an increased number of colored bars in response to increasing concentrations of H2O2. The video is further described in article 3.

Video of analog dial devices following the addition of sample containing H2O2 with a fixed assay time of 10 minutes. The three devices shown are exposed to 25, 50 and 100 mM H2O2 respectively. The video shows an increased number of colored bars in response to increasing concentrations of H2O2. The video is further described in article 3.

Examples of our recent publications in this area:

  1. "A Point-of-Use Assay That Measures Heavy Metal Contamination in Water Using Time as a Quantitative Readout", Lewis, G. G.; Robbins, J. S.; Phillips, S. T.*, Chem. Commun., DOI: 10.1039/C3CC47698G.

  2. "Quantitative Fluorescence Assays Using a Self-Powered Paper-Based Microfluidic Device and a Camera-Equipped Cellular Phone", Thom, N. K.; Lewis, G. G.; Yeung, K.; Phillips, S. T.*, RSC Adv., accepted. DOI:10.1039/C3RA44717K.

  3. "A Rapid Point-of-Care Assay Platform for Quantifying Active Enzymes to Femtomolar Levels Using Measurements of Time as the Readout", Lewis, G. G.; Robbins, J. S.; Phillips, S. T.*, Analytical Chemistry, 2013, 85, 10432–10439.

  4. "Phase-Switching Depolymerizable Poly(carbamate) Oligomers for Signal Amplification in Quantitative Time-Based Assays", Lewis, G. G.; Robbins, J. S.; Phillips, S. T.*, Macromolecules, 46, 5177–5183.

  5. "Reagents and Assay Strategies for Quantifying Active Enzyme Analytes Using a Personal Glucose Meter", Mohapatra, H.; Phillips, S. T.*, Chem. Commun., 2013, 49, 6134–6136.

  6. "Two General Designs for Fluidic Batteries in Paper-Based Microfluidic Devices That Provide Predictable and Tunable Sources of Power for On-Chip Assays", Thom, N. K.; Lewis, G. G.; DiTucci, M. J.; Phillips, S. T.*, RSC Adv., 2013, 3, 6888–6895.

  7. "Phase Switching to Enable Highly Selective Activity-Based Assays", Mohapatra, H.; Phillips, S. T.*, Anal. Chem., 2012, 84, 8927–8931.

  8. "Quantifying Analytes in Paper-Based Microfluidic Devices Without Using External Electronic Readers", Lewis, G. G.; DiTucci, M. J.; Phillips, S. T.*, Angew. Chem. Int. Ed., 2012, 51, 12707–12710.

  9. "Using Smell to Triage Samples in Point-of-Care Assays", Mohapatra, H.; Phillips, S. T.*, Angew. Chem. Int. Ed., 2012, 44, 11145–11148.

  10. "High Throughput Method for Prototyping Three-Dimensional, Paper-Based Microfluidic Devices", Lewis, G. G.; DiTucci, M. J.; Baker, M. S.; Phillips, S. T.*, Lab Chip, 2012, 12, 2630–2633.

  11. "Fluidic Batteries in Paper-Based Microfluidic Devices", Thom, N. K., Yeung, K., Pillion, M. B., Phillips, S. T.* Lab Chip, 2012, 12, 1768–1770.

  12. "A Small Molecule Sensor for Fluoride Based on an Autoinductive, Colorimetric Signal Amplification Reaction", Baker, M. S.; Phillips, S. T.*, Org. Biomol. Chem., 2012, 10, 3595–3599.

  13. "Fluidic "Timers" for Paper-Based Microfluidic Devices", Noh, H., Phillips, S. T.*, Anal. Chem. 2010, 82, 8071–8078.

  14. "Metering the Capillary-driven Flow of Fluids in Paper-Based Microfluidic Devices", Noh, H., Phillips, S. T.*, Anal. Chem. 2010, 82, 4181–4187.

Stimuli-Responsive Materials


We seek to create new approaches for designing plastics that change their shape, function, surface properties, etc. in response to their environment. Traditional materials made out of plastics are static objects with a single use. Plastics with autonomous response properties, however, should be capable of more than one function. Moreover, if designed correctly, these autonomous plastics will be easy to recycle. In pursuit of these characteristics, we are developing polymers (and plastics made from them) that detect specific signals in the environment and then respond to those signals quickly with amplified responses. Example applications that are currently being explored in the group include: (i) shape-shifting, remodeling, and vanishing materials; (ii) low-energy strategies for recycling plastics; (iii) corrosion-indicator coatings; and (iv) smart biomedical materials.

Video of fluoride responsive poly(phthalaldehyde) depolymerizing in the presence of fluoride (16x speed)

Video of poly(phthalaldehyde) depolymerizing in response to beta-D-glucuronidase. Released monomers create a concentration gradient that pumps microscopic tracer particles away from the site (25x speed)

Examples of our recent publications in this area:

  1. "Improving the Accessibility of Responsive End-Caps in Films Composed of Stimuli-Responsive Depolymerizable Poly(phthalaldehydes)", DiLauro, A. M.; Zhang, H.; Baker, M. S.; Wong, F.; Sen, A.; Phillips, S. T.*, Macromolecules, 2013, 46, 7257–7265.

  2. "A Self-Powered Polymeric Material that Responds Autonomously and Continuously to Fleeting Stimuli", Baker, M. S.; Yadav, V.; Sen, A.*; Phillips, S. T.*, Angew. Chem. Int. Ed., 52, 10295–10299.

  3. "End-Capped Poly(benzyl ethers): Acid and Base Stable Polymers That Depolymerize Rapidly from Head-to-Tail in Response to Specific Applied Signals", Olah, M. G.; Robbins, J. S.; Baker, M. S.; Phillips, S. T.*, Macromolecules, 2013, 46, 5924–5928.

  4. "Stimuli-Responsive Core-Shell Microcapsules With Tunable Rates of Release by Using a Depolymerizable Poly(phthalaldehyde) Membrane", DiLauro, A. M.; Abbaspourrad, A.; Weitz, D. A.; Phillips, S. T.*, Macromolecules, 2013, 46, 3309–3313.

  5. "Effect of Aromaticity on the Rate of Azaquinone Methide-Mediated Release of Benzylic Phenols", Schmid, K. M.; Phillips, S. T.*, J. Phys. Org. Chem., 2013, 26, 608–610.

  6. "Effects of Electronics, Aromaticity, and Solvent Polarity on the Rate of Azaquinone-Methide-Mediated Depolymerization of Aromatic Carbamate Oligomers", Robbins, J. S.; Schmid, K. M; Phillips, S. T.*, J. Org. Chem., 2013, 3159–3169.

  7. "Reproducible and Scalable Synthesis of End-Cap-Functionalized Depolymerizable Poly(phthalaldehydes)", DiLauro, A.; Robbins, J. S.; Phillips, S. T.*, Macromolecules, 2013, 46, 2963–2968.

  8. "A Self-Immolative Spacer that Enables Tunable Controlled Release of Phenols under Neutral Conditions", Schmid, K. M.; Jensen, L.; Phillips, S. T.*, J. Org. Chem., 2012, 77, 4363–4374.

  9. "Self-Powered Microscale Pumps Based on Analyte-Initiated Depolymerization Reactions", Zhang, H.; Yeung, K.; Robbins, J. S.; Pavlick, R. A.; Wu, M.; Liu, R.; Sen*, A.; Phillips, S. T.*, Angew. Chem. Int. Ed. 2012, 51, 2400–2404.

  10. "Patterned Plastics that Change Physical Structure in Response to Applied Chemical Signals", Seo, W.; Phillips, S. T.*, J. Am. Chem. Soc. 2010, 132, 9234–9235.

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