Hsiang-Hua Hung

All Publications

• Tunable Applicator for Microneedle-Based Medical Devices ADVANCED MATERIALS TECHNOLOGIES Ilyn, D., Hwang, J., Coates, I. A., Dobson, J., Hung, A. H., Kamat, N. U., Tumbleston, J. R., Dulay, M. T., Jacobson, G. B., DeSimone, J. M. 2026

  View details for DOI 10.1002/admt.202502525

  View details for Web of Science ID 001687405100001

• A microneedle device for rapid dermal interstitial fluid sampling. Science advances Hung, A. H., Kamat, N. U., Bermudez, A., Boczek, S. M., Garcia-Marqués, F. J., Tan, Y. L., Hwang, J. L., Sinawang, P. D., Ilyin, D., Jacobson, G. B., Demirci, U., Poplack, S. P., Pitteri, S. J., DeSimone, J. M. 2025; 11 (39): eadx5492

  Abstract

  Dermal interstitial fluid (ISF) offers a promising alternative to invasive blood tests and opportunities for skin diagnostics. Progress in both the understanding and adoption of ISF tests is hindered by sampling challenges, including lengthy collection times, non-negligible failure rates, variable collection volumes, and inconsistent bioanalyte levels. The causes of many of these issues are not well understood. We demonstrate a microneedle device that is several times faster than state of the art, collecting an average of 15.5 mg of ISF in 5 minutes in humans with near-zero failure rate. This improvement was achieved by designing the spatial pressure gradient driving ISF flow. The influence of penetration depth, collection time, pressure, and age on ISF collection was elucidated, with Darcy's law explaining multiple observations. A data-driven acceptance criterion of <1% blood contamination for ISF is proposed. The device and findings presented will empower researchers to better conduct robust studies in the development of ISF diagnostics.

  View details for DOI 10.1126/sciadv.adx5492

  View details for PubMedID 40991687

  View details for PubMedCentralID PMC12459406

• 3D-Printed Latticed Microneedle Array Patches for Tunable and Versatile Intradermal Delivery. Advanced materials (Deerfield Beach, Fla.) Rajesh, N. U., Luna Hwang, J., Xu, Y., Saccone, M. A., Hung, A. H., Hernandez, R. A., Coates, I. A., Driskill, M. M., Dulay, M. T., Jacobson, G. B., Tian, S., Perry, J. L., DeSimone, J. M. 2024: e2404606

  Abstract

  Using high-resolution 3D printing, a novel class of microneedle array patches (MAPs) is introduced, called latticed MAPs (L-MAPs). Unlike most MAPs which are composed of either solid structures or hollow needles, L-MAPs incorporate tapered struts that form hollow cells capable of trapping liquid droplets. The lattice structures can also be coated with traditional viscous coating formulations, enabling both liquid- and solid-state cargo delivery, on a single patch. Here, a library of 43 L-MAP designs is generated and in-silico modeling is used to down-select optimal geometries for further characterization. Compared to traditionally molded and solid-coated MAPs, L-MAPs can load more cargo with fewer needles per patch, enhancing cargo loading and drug delivery capabilities. Further, L-MAP cargo release kinetics into the skin can be tuned based on formulation and needle geometry. In this work, the utility of L-MAPs as a platform is demonstrated for the delivery of small molecules, mRNA lipid nanoparticles, and solid-state ovalbumin protein. In addition, the production of programmable L-MAPs is demonstrated with tunable cargo release profiles, enabled by combining needle geometries on a single patch.

  View details for DOI 10.1002/adma.202404606

  View details for PubMedID 39221508

• Magnetic Barcode Imaging for Contrast Agents MAGNETIC RESONANCE IN MEDICINE Hung, A. H., Lilley, L. M., Hu, F., Harrison, V. S. R., Meade, T. J. 2017; 77 (3): 970-978

  Abstract

  To demonstrate a new MR imaging approach that unambiguously identifies and quantitates contrast agents based on intrinsic agent properties such as r1 , r2 , r2*, and magnetic susceptibility. The approach is referred to as magnetic barcode imaging (MBI).Targeted and bioresponsive contrast agents were imaged in agarose phantoms to generate T1 , T2 , T2*, and quantitative susceptibility maps. The parameter maps were processed by a machine learning algorithm that is trained to recognize the contrast agents based on these parameters. The output is a quantitative map of contrast agent concentration, identity, and functional state.MBI allowed the quantitative interpretation of intensities, removed confounding backgrounds, enabled contrast agent multiplexing, and unambiguously detected the activation and binding states of bioresponsive and targeted contrast agents.MBI has the potential to overcome significant limitations in the interpretation, quantitation, and multiplexing of contrast enhancement by MR imaging probes. Magn Reson Med 77:970-978, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26175

  View details for Web of Science ID 000397407800007

  View details for PubMedID 27062518

  View details for PubMedCentralID PMC5055837

• Graphene Oxide Enhances Cellular Delivery of Hydrophilic Small Molecules by Co-incubation ACS NANO Hung, A. H., Holbrook, R. J., Rotz, M. W., Glasscock, C. J., Mansukhani, N. D., MacRenaris, K. W., Manus, L. M., Duch, M. C., Dam, K. T., Hersam, M. C., Meade, T. J. 2014; 8 (10): 10168-10177

  Abstract

  The delivery of bioactive molecules into cells has broad applications in biology and medicine. Polymer-modified graphene oxide (GO) has recently emerged as a de facto noncovalent vehicle for hydrophobic drugs. Here, we investigate a different approach using native GO to deliver hydrophilic molecules by co-incubation in culture. GO adsorption and delivery were systematically studied with a library of 15 molecules synthesized with Gd(III) labels to enable quantitation. Amines were revealed to be a key chemical group for adsorption, while delivery was shown to be quantitatively predictable by molecular adsorption, GO sedimentation, and GO size. GO co-incubation was shown to enhance delivery by up to 13-fold and allowed for a 100-fold increase in molecular incubation concentration compared to the alternative of nanoconjugation. When tested in the application of Gd(III) cellular MRI, these advantages led to a nearly 10-fold improvement in sensitivity over the state-of-the-art. GO co-incubation is an effective method of cellular delivery that is easily adoptable by researchers across all fields.

  View details for DOI 10.1021/nn502986e

  View details for Web of Science ID 000343952600050

  View details for PubMedID 25226566

  View details for PubMedCentralID PMC4212791

• Cell Labeling via Membrane-Anchored Lipophilic MR Contrast Agents BIOCONJUGATE CHEMISTRY Carney, C. E., MacRenaris, K. W., Mastarone, D. J., Kasjanski, D. R., Hung, A. H., Meade, T. J. 2014; 25 (5): 945-954

  Abstract

  Cell tracking in vivo with MR imaging requires the development of contrast agents with increased sensitivity that effectively label and are retained by cells. Most clinically approved Gd(III)-based contrast agents require high incubation concentrations and prolonged incubation times for cellular internalization. Strategies to increase contrast agent permeability have included conjugating Gd(III) complexes to cell penetrating peptides, nanoparticles, and small molecules which have greatly improved cell labeling but have not resulted in improved cellular retention. To overcome these challenges, we have synthesized a series of lipophilic Gd(III)-based MR contrast agents that label cell membranes in vitro. Two of the agents were synthesized with a multiplexing strategy to contain three Gd(III) chelates (1 and 2) while the third contains a single Gd(III) chelate (3). These new agents exhibit significantly enhanced labeling and retention in HeLa and MDA-MB-231-mcherry cells compared to agents that are internalized by cells (4 and Prohance).

  View details for DOI 10.1021/bc500083t

  View details for Web of Science ID 000336416800013

  View details for PubMedID 24787689

  View details for PubMedCentralID PMC4033656

• High Dynamic Range Processing for Magnetic Resonance Imaging PLOS ONE Hung, A. H., Liang, T., Sukerkar, P. A., Meade, T. J. 2013; 8 (11): e77883

  Abstract

  To minimize feature loss in T1- and T2-weighted MRI by merging multiple MR images acquired at different TR and TE to generate an image with increased dynamic range.High Dynamic Range (HDR) processing techniques from the field of photography were applied to a series of acquired MR images. Specifically, a method to parameterize the algorithm for MRI data was developed and tested. T1- and T2-weighted images of a number of contrast agent phantoms and a live mouse were acquired with varying TR and TE parameters. The images were computationally merged to produce HDR-MR images. All acquisitions were performed on a 7.05 T Bruker PharmaScan with a multi-echo spin echo pulse sequence.HDR-MRI delineated bright and dark features that were either saturated or indistinguishable from background in standard T1- and T2-weighted MRI. The increased dynamic range preserved intensity gradation over a larger range of T1 and T2 in phantoms and revealed more anatomical features in vivo.We have developed and tested a method to apply HDR processing to MR images. The increased dynamic range of HDR-MR images as compared to standard T1- and T2-weighted images minimizes feature loss caused by magnetization recovery or low SNR.

  View details for DOI 10.1371/journal.pone.0077883

  View details for Web of Science ID 000327216200009

  View details for PubMedID 24250788

  View details for PubMedCentralID PMC3826760

• Mechanisms of Gadographene-Mediated Proton Spin Relaxation JOURNAL OF PHYSICAL CHEMISTRY C Hung, A. H., Duch, M. C., Parigi, G., Rotz, M. W., Manus, L. M., Mastarone, D. J., Dam, K. T., Gits, C. C., MacRenaris, K. W., Luchinat, C., Hersam, M. C., Meade, T. J. 2013; 117 (31): 16263-16273

  Abstract

  Gd(III) associated with carbon nanomaterials relaxes water proton spins at an effectiveness that approaches or exceeds the theoretical limit for a single bound water molecule. These Gd(III)-labeled materials represent a potential breakthrough in sensitivity for Gd(III)-based contrast agents used for magnetic resonance imaging (MRI). However, their mechanism of action remains unclear. A gadographene library encompassing GdCl3, two different Gd(III)-complexes, graphene oxide (GO), and graphene suspended by two different surfactants and subjected to varying degrees of sonication was prepared and characterized for their relaxometric properties. Gadographene was found to perform comparably to other Gd(III)-carbon nanomaterials; its longitudinal (r1) and transverse (r2) relaxivity is modulated between 12-85 mM-1s-1 and 24-115 mM-1s-1, respectively, depending on the Gd(III)-carbon backbone combination. The unusually large relaxivity and its variance can be understood under the modified Florence model incorporating the Lipari-Szabo approach. Changes in hydration number (q), water residence time (τM), molecular tumbling rate (τR), and local motion (τfast) sufficiently explain most of the measured relaxivities. Furthermore, results implicated the coupling between graphene and Gd(III) as a minor contributor to proton spin relaxation.

  View details for DOI 10.1021/jp406909b

  View details for Web of Science ID 000323082300049

  View details for PubMedID 24298299

  View details for PubMedCentralID PMC3843495

• Analytical Methods for Characterizing Magnetic Resonance Probes ANALYTICAL CHEMISTRY Manus, L. M., Strauch, R. C., Hung, A. H., Eckermann, A. L., Meade, T. J. 2012; 84 (15): 6278-6287

  Abstract

  The efficiency of Gd(III) contrast agents in magnetic resonance image enhancement is governed by a set of tunable structural parameters. Understanding and measuring these parameters requires specific analytical techniques. This Feature describes strategies to optimize each of the critical Gd(III) relaxation parameters for molecular imaging applications and the methods employed for their evaluation.

  View details for DOI 10.1021/ac300527z

  View details for Web of Science ID 000307159200002

  View details for PubMedID 22624599

  View details for PubMedCentralID PMC3418482

• Hydrogel-elastomer composite biomaterials: 4. Experimental optimization of hydrogel-elastomer composite fibers for use as a wound dressing Peng, H. T., Martineau, L., Hung, A. SPRINGER. 2008: 1803-1813

  Abstract

  We report a novel 3-D cavity wound dressing based on a hydrogel-elastomer Interpenetrating Polymer Network (IPN) fabricated into an open-mesh architecture. IPN fibers used to form the dressing were produced by a wet spinning method and optimized in two steps. A factorial experiment was first conducted to identify key parameters that controlled fiber properties. We observed that gelatin wt% played a major role in determining fiber yield, swelling, strength and stability. Other contributing factors included coagulation solution composition, gelatin type, and pre- and post-UV irradiation time. The key factors were then further evaluated individually to achieve a condition that provided a combination of good swelling, mechanical properties and stability. The concentration of the gelatin/HydroThane extrusion solution significantly affected fiber formation and properties, presumably due to the changes in solution viscosity. The effects of pre-UV irradiation were also ascribed to its impact on the solution viscosity and became negligible at higher concentrations when viscosity is mainly controlled by concentration. The composition of the coagulation bath influenced the fiber swelling and wet stress. These results, taken together with our previous studies, suggest that our biomaterial would provide a combination of mechanical and swelling properties suitable for wound dressing applications.

  View details for DOI 10.1007/s10856-007-3324-y

  View details for Web of Science ID 000253976200048

  View details for PubMedID 18058199

• Toward the accurate read-out of quantum dot barcodes: Design of deconvolution algorithms and assessment of fluorescence signals in buffer ADVANCED MATERIALS Lee, J. A., Mardyani, S., Hung, A., Rhee, A., Klostranec, J., Mu, Y., Li, D., Chan, W. C. W. 2007; 19 (20): 3113-+

  View details for DOI 10.1002/adma.200701955

  View details for Web of Science ID 000250735600005

• Controlling methicillin resistant <i>Staphyloccocus aureus</i> and <i>Pseudomonas aeruginosa</i> wound infections with a novel biomaterial JOURNAL OF INVESTIGATIVE SURGERY Martineau, L., Davis, S. C. 2007; 20 (4): 217-227

  Abstract

  Wound infections, especially those associated with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, offer considerable challenges for clinicians. Our laboratory has recently developed novel composite biomaterials (DRDC) for wound dressing applications, and demonstrated their in vitro bactericidal efficacy. In the present study, we assessed the proliferation of planktonic and sessile Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in porcine full-thickness wounds covered for up to 48 h with either saline- or mafenide acetate-loaded DRDC puffs and meshes. All biomaterials were applied 4 h following bacterial inoculation of the wounds with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, to allow colonization of the tissues and initiation of biofilm formation. The drug-loaded biomaterials eradicated both the planktonic and biofilm bacteria in the wounds within 24 h (p <. 05), irrespective of the bacterial strain or architecture of the dressing. While the wound bioburdens increased in the ensuing 24 h, they remained approximately 2 log(10) colony-forming units (CFU) below (p <. 05) their respective baseline values. Similarly, less than 4 log(10) CFU was recovered in the drug-loaded DRDC biomaterials throughout the study. These data show that the DRDC puffs and meshes are effective in delivering certain medications, such as antimicrobial agents, to the wound bed, suggesting considerable value of this material for treating wounds, especially those with irregular shapes, contours, and depths.

  View details for DOI 10.1080/10717540701481275

  View details for Web of Science ID 000248809700003

  View details for PubMedID 17710602