Michael Cima | Massachusetts Institute of Technology (MIT) (original) (raw)

Papers by Michael Cima

Science translational medicine, Jan 22, 2015

Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic marker... more Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure...

PLOS ONE, 2015

Atherosclerosis and malignancy are pervasive pathological conditions that account for the bulk of... more Atherosclerosis and malignancy are pervasive pathological conditions that account for the bulk of morbidity and mortality in developed countries. Our current understanding of the patholobiology of these fundamental disorders suggests that inflammatory processes may differentially affect them; thus, atherosclerosis can be largely driven by inflammation, where as cancer often flourishes as inflammatory responses are modulated. A corollary of this hypothesis is that cancer (or its treatment may significantly attenuate atherosclerotic disease by diminishing host inflammatory response, suggesting potential therapeutic approaches. To evaluate the relationship between cancer and cardiovascular atherosclerotic disease, we assessed 1,024 autopsy reports from Brigham and Women's Hospital and performed correlative analyses on atherosclerotic severity and cancer prevalence. In gender- and age-matched populations, there is a statistically significant inverse correlation between history of malignancy and autopsy-proven atherosclerotic disease. In a second analysis, we evaluated 147,779 patients through analysis of the Harvard Catalyst SHRINE database and demonstrated a reduced non-coronary atherosclerotic disease rate: control (27.40%), leukemia/lymphoma (12.57%), lung (17.63%), colorectal (18.17%), breast (9.79%), uterus/cervix (11.47%), and prostate (18.40%). We herein report that, based on two separate medical records analysis, an inverse correlation between cancer and atherosclerosis. Furthermore, this correlation is not uniformly associated with anti-neoplastic treatment, suggesting that the inverse relationship may be in part attributable to an individual's intrinsic inflammatory propensity, and/or to inflammation-modulatory properties of neoplasms.

Materials & Design, 1999

Solid Freeform Fabrication SFF processes have demonstrated the ability to produce parts with loca... more Solid Freeform Fabrication SFF processes have demonstrated the ability to produce parts with locally controlled composition. In the limit, processes such as 3D Printing can create parts with composition control on a length scale of 100 m. To exploit this potential, new methods to model, exchange, and process parts with local composition control need to be developed. An approach to modeling a part's geometry, topology, and composition is presented. This approach is based on subdividing the solid model into sub-regions and associating analytic composition blending functions with each region. These blending functions de ne the composition throughout the model as mixtures of the primary materials available to the SFF machine. Design tools based u p on distance functions are also introduced, such as the speci cation of composition as a function of the distance from the surface of a part. Finally, the role of design rules restricting maximum and minimum concentrations is discussed.

Biomaterials, 2005

The component materials of controlled-release drug delivery systems are often selected based on t... more The component materials of controlled-release drug delivery systems are often selected based on their degradation rates. The release time of a drug from a system will strongly depend on the degradation rates of the component polymers. We have observed that some poly(lactic-co-glycolic acid) polymers (PLGA) exhibit degradation rates that depend on the size of the polymer object and the temperature

Journal of Materials Research, 1994

Heteroepitxial growth of Ba2YCu3O7-x (BYC) thin films prepared by postdeposition annealing on (00... more Heteroepitxial growth of Ba2YCu3O7-x (BYC) thin films prepared by postdeposition annealing on (001) LaAlO3 was characterised by TEM and XRD studies of specimens rapidly cooled from various points in the growth heat treatment. Heteroepitaxial nucleation ...

Chronopharmaceutics, 2009

Page 1. CHAPTER 9 CONTROLLED RELEASE MICROCHIPS KAREN DANIEL, HONG LINH HO DUC, MICHAEL CIMA, and... more Page 1. CHAPTER 9 CONTROLLED RELEASE MICROCHIPS KAREN DANIEL, HONG LINH HO DUC, MICHAEL CIMA, and ROBERT LANGER ''Our brains are seventy-year clocks. The Angel of Life winds them up once for ...

Science Translational Medicine, 2012

Limited treatment options exist for patients who suffer from a painful bladder condition known as... more Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because their concentrations in the bladder are low. A previous attempt to develop a drug delivery device for use in the bladder was unsuccessful, likely as a result of poor tolerability. A continuous lidocaine-releasing intravesical system (LiRIS) was designed to be retained in the bladder and release therapeutic amounts of the drug into urine over a period of 2 weeks. The device was tested in healthy volunteers and IC/BPS patients and was found to be well tolerated in both subject groups because of its small size and freedom of movement within the bladder. The 16 women with IC/BPS who were enrolled in the study met the National Institute of Diabetes and Digestive and Kidney Diseases criteria for bladder hemorrhages or Hunner's lesions. Subjects received either LiRIS 200 mg or LiRIS 650 mg for 2 weeks. Safety, efficacy, cystoscopic appearance of the bladder, and limited pharmacokinetic data were collected. Both doses were well tolerated, and clinically meaningful reductions were seen in pain, urgency, voiding frequency, and disease questionnaires. Cystoscopic examinations showed improvement on day 14 (day of removal) compared with day 1, including resolution of Hunner's lesions in five of six subjects with baseline lesions. Global response assessment showed an overall responder rate of 64% at day 14 and a sustained overall responder rate of 64% 2 weeks later. Extended follow-up suggests that the reduction in pain was maintained for several months after the device was removed.

Proceedings of the IEEE, 2004

MEMS devices are manufactured using similar microfabrication techniques as those used to create i... more MEMS devices are manufactured using similar microfabrication techniques as those used to create integrated circuits. They often, however, have moving components that allow physical or analytical functions to be performed by the device. Although MEMS can be aseptically fabricated and hermetically sealed, biocompatibility of the component materials is a key issue for MEMS used in vivo. Interest in MEMS for biological applications (BioMEMS) is growing rapidly, with opportunities in areas such as biosensors, pacemakers, immunoisolation capsules, and drug delivery. The key to many of these applications lies in the leveraging of features unique to MEMS (for example, analyte sensitivity, electrical responsiveness, temporal control, and feature sizes similar to cells and organelles) for maximum impact. In this paper, we focus on how the biological integration of MEMS and other implantable devices can be improved through the application of microfabrication technology and concepts. Innovative approaches for improved physical and chemical integration of systems with the body are reviewed. An untapped potential for MEMS may lie in the area of nervous and endocrine system actuation, whereby the ability of MEMS to deliver potent drugs or hormones, combined with their precise temporal control, may provide new treatments for disorders of these systems.

Polymer Engineering & Science, 2000

Three Dimensional Printing is a desktop manufacturing process in which powdered materials are dep... more Three Dimensional Printing is a desktop manufacturing process in which powdered materials are deposited in layers and selectively joined with binder from an ink-jet style printhead. Unbound powder is removed upon process completion, leaving a three dimensional part. Stainless steel injection molding inserts have been created from metal powder with the 3DP process.

Physica C: Superconductivity, 2004

Precursor films prepared by metal organic deposition are shown to be much richer in fluorine than... more Precursor films prepared by metal organic deposition are shown to be much richer in fluorine than previously suspected. The ratio of fluorine to barium is 2.7 when the film is prepared at 400°C and decreases with increasing temperature. That is, the films contain more fluorine than can be explained by only barium fluoride being present. The remaining F/Ba ratio trajectory of MOD decreases from 2.7 to about 1.5 without the formation of detectable Ba 2 YCu 3 O 6:5 (YBCO). The trajectory is also shown to include compositions known to contain low melting liquids. These observations show that YBCO formation from MOD-derived precursor occurs in multiple steps: (1) decomposition of YF 3 , (2) decomposition of BaF 2 without YBCO nucleation, (3) formation of YBCO via liquid phase. This means small amount of oxyfluoride melt is present in the film during the conversion to YBCO. Thicker films have a larger F/Ba ratio at any given temperature which possibly leads to more melt. The melt may contribute to the densification and the epitaxial growth of YBCO. It may also, however, cause reaction with substrate and/or buffer layer.

Pharmaceutical Research, 2006

Micro-and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become ... more Micro-and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become commercially-feasible due to converging technologies and regulatory accommodation. The FDA Office of Combination Products coordinates review of innovative medical therapies that join elements from multiple established categories: drugs, devices, and biologics. Combination products constructed using MEMS or NEMS technology offer revolutionary opportunities to address unmet medical needs related to dosing. These products have the potential to completely control drug release, meeting requirements for on-demand pulsatile or adjustable continuous administration for extended periods. MEMS or NEMS technologies, materials science, data management, and biological science have all significantly developed in recent years, providing a multidisciplinary foundation for developing integrated therapeutic systems. If small-scale biosensor and drug reservoir units are combined and implanted, a wireless integrated system can regulate drug release, receive sensor feedback, and transmit updates. For example, an Bartificial pancreas^implementation of an integrated therapeutic system would improve diabetes management. The tools of microfabrication technology, information science, and systems biology are being combined to design increasingly sophisticated drug delivery systems that promise to significantly improve medical care.

Pharmaceutical compounds are molecular solids that frequently exhibit polymorphism of crystal for... more Pharmaceutical compounds are molecular solids that frequently exhibit polymorphism of crystal form. One high profile case of polymorphism was ritonavir, a peptidomimetic drug used to treat HIV-1 infection and introduced in 1996. In 1998, a lower energy, more stable polymorph (form II) appeared, causing slowed dissolution of the marketed dosage form and compromising the oral bioavailability of the drug. This event forced the removal of the oral capsule formulation from the market. We have carried out high-throughput crystallization experiments to comprehensively explore ritonavir form diversity. A total of five forms were found: both known forms and three previously unknown forms. The novel forms include a metastable polymorph, a hydrate phase, and a formamide solvate. The solvate was converted to form I via the hydrate phase by using a simple washing procedure, providing an unusual route to prepare the form I ''disappearing polymorph'' [Dunitz, J. D. & Bernstein, J. (1995) Acc. Chem. Res. 28, 193-200].

Journal of Materials Research - J MATER RES, 1998

ABSTRACT A new quenching technique was used for detailed microstructural examination of quenched ... more ABSTRACT A new quenching technique was used for detailed microstructural examination of quenched YBa2Cu3O6+δ/liquid interfaces. The examination revealed that the growth rate and the amount of excess Y2BaCuO5 (211) had a strong influence on the growth morphology of YBa2Cu3O6+δ (123). The maximum growth rate at which single crystal growth could be obtained increased from 1 μm/s to 1.5 μm/s as excess 211 content increased from 0 to 20 wt. %. It then decreased to 1 μm/s as excess 211 increased to 40 wt. %. Dendritic growth with distinguishable secondary arms occurred for stoichiometric 123 samples in the regime of cellular/dendritic growth. A highly curved 123 envelope was formed on 211 particles located at the 123 growth interface for stoichiometric 123 samples in the regime of single crystal growth. The microscopic 123 growth interface became flat as excess 211 content increased to 20 wt. %. The engulfment of 211 particles into 123 matrix is discussed based on detailed microstructural examination. It is found that the formation of a small highly curved 123 envelope on 211 particles for stoichiometric 123 samples is due to the large 211 particle spacing.

Nature Materials, 2003

nature materials | VOL 2 | NOVEMBER 2003 | www.nature.com/naturematerials 767 T he method by whic... more nature materials | VOL 2 | NOVEMBER 2003 | www.nature.com/naturematerials 767 T he method by which a drug is delivered can have a significant effect on the drug's therapeutic efficacy 1 . Conventional drug delivery systems such as implants and some oral delivery systems typically produce a sharp initial increase in drug concentration to a peak above the therapeutic range, followed by a fast decrease in concentration to a level below the therapeutic range. The time spent in the optimum concentration range for therapeutic effect is therefore short 2 . Initial concentration peaks can pose a serious risk of toxicity and related complications for potent drugs. Additionally, accurate and repeatable dosing of medication to patients may be difficult to achieve because of patient non-compliance. The field of controlled-release drug delivery therefore initially focused on achieving a constant release of drug over long periods with minimal influence by outside factors. However,for certain molecules or drugs,sustained or continuous release is not optimal. For example, insulin 3 and hormones of the anterior pituitary gland such as growth hormone and gonadotropin-releasing hormone (GnRH) are secreted by the human body in a pulsatile fashion 4 . It is desirable for therapies that treat deficiencies or disorders of these molecules to mimic the pulsatile fashion in which the molecules are naturally released from the body. Similarly, for multi-dose vaccines, repeated delivery of the antigen is desired for optimal antibody response.

Materials Science and Engineering: A, 2001

Carbon performs have been fabricated using the three-dimensional printing (3DP™) process for reac... more Carbon performs have been fabricated using the three-dimensional printing (3DP™) process for reaction-infiltrated SiC-Si composites. Starting with glassy carbon powders of 45 -105 mm sizes, the preform was produced by printing acetone-based furfuryl resin binder. The bulk density and open porosity of the resulting preform was 0.6 g cm − 3 and 48%, respectively. The binder printing conditions during preform fabrication mostly determined the preform microstructure. Pressureless reactive infiltration of such preforms at 1450°C in nitrogen atmosphere formed a SiC -Si composite with a coarse-SiC grain structure. Some residual carbon remained inside the SiC grains in this reaction bonded SiC -C due to sluggish reactivity of the larger carbon powder particles. Relatively complex-shaped carbon preforms with overhang, undercut, and inner channel structures were produced, demonstrating the capability of the 3DP process. A functionally graded SiC -Si composite was also fabricated, by varying carbon-yielding binder dosage during the preform fabrication, in order to control the spatial SiC concentration within the SiC-Si composite.

Langmuir, 2003

Undecanethiol (C11H23SH) and tri(ethylene glycol)-terminated undecanethiol (HO(C2H4O)3C11H22SH) s... more Undecanethiol (C11H23SH) and tri(ethylene glycol)-terminated undecanethiol (HO(C2H4O)3C11H22SH) self-assembled monolayers (SAMs) on clean gold surfaces were prepared and characterized. The SAMs were then immersed into either phosphate-buffered saline or calf serum. The SAM samples were investigated using several analytical techniques at numerous points over the next 35 days. Contact angles and current densities in voltammetry changed dramatically for the PBS samples over the time period, particularly after 21 days. Results indicate substantial loss of the integrity of the SAM. Similar alterations with time were observed for the calf serum samples in both contact angle and voltammetry measurements. X-ray photoelectron spectroscopy indicates that the likely origin is desorption of the alkanethiol moiety as evidenced by appreciable loss of the S 2p signal after 35 days.

Lab on a Chip, 2007

By combining the sensing capabilities of nanoscale magnetic relaxation switches (MRS) within mult... more By combining the sensing capabilities of nanoscale magnetic relaxation switches (MRS) within multi-reservoir structures, a potentially powerful implantable multiplexed sensor has been developed. MRS are magnetic nanoparticles that decrease the transverse relaxation time (T(2)) of water in the presence of an analyte. The switches encased in polydimethylsiloxane (PDMS) devices with polycarbonate membranes (10 nm pores) have demonstrated in vitro sensing of the beta subunit of human chorionic gonadotrophin (hCG-beta), which is elevated in testicular and ovarian cancer. Devices showed transverse relaxation time (T(2)) shortening by magnetic resonance imaging (MRI) when incubated in analyte solutions of 0.5 to 5 microg hCG-beta mL(-1). The decrease in T(2) was between 9% and 27% (compared to control devices) after approximately 28 h. This prototype device is an important first step in developing an implantable sensor for detecting soluble cancer biomarkers in vivo.

Science translational medicine, Jan 22, 2015

Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic marker... more Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure...

PLOS ONE, 2015

Atherosclerosis and malignancy are pervasive pathological conditions that account for the bulk of... more Atherosclerosis and malignancy are pervasive pathological conditions that account for the bulk of morbidity and mortality in developed countries. Our current understanding of the patholobiology of these fundamental disorders suggests that inflammatory processes may differentially affect them; thus, atherosclerosis can be largely driven by inflammation, where as cancer often flourishes as inflammatory responses are modulated. A corollary of this hypothesis is that cancer (or its treatment may significantly attenuate atherosclerotic disease by diminishing host inflammatory response, suggesting potential therapeutic approaches. To evaluate the relationship between cancer and cardiovascular atherosclerotic disease, we assessed 1,024 autopsy reports from Brigham and Women's Hospital and performed correlative analyses on atherosclerotic severity and cancer prevalence. In gender- and age-matched populations, there is a statistically significant inverse correlation between history of malignancy and autopsy-proven atherosclerotic disease. In a second analysis, we evaluated 147,779 patients through analysis of the Harvard Catalyst SHRINE database and demonstrated a reduced non-coronary atherosclerotic disease rate: control (27.40%), leukemia/lymphoma (12.57%), lung (17.63%), colorectal (18.17%), breast (9.79%), uterus/cervix (11.47%), and prostate (18.40%). We herein report that, based on two separate medical records analysis, an inverse correlation between cancer and atherosclerosis. Furthermore, this correlation is not uniformly associated with anti-neoplastic treatment, suggesting that the inverse relationship may be in part attributable to an individual's intrinsic inflammatory propensity, and/or to inflammation-modulatory properties of neoplasms.

Materials & Design, 1999

Solid Freeform Fabrication SFF processes have demonstrated the ability to produce parts with loca... more Solid Freeform Fabrication SFF processes have demonstrated the ability to produce parts with locally controlled composition. In the limit, processes such as 3D Printing can create parts with composition control on a length scale of 100 m. To exploit this potential, new methods to model, exchange, and process parts with local composition control need to be developed. An approach to modeling a part's geometry, topology, and composition is presented. This approach is based on subdividing the solid model into sub-regions and associating analytic composition blending functions with each region. These blending functions de ne the composition throughout the model as mixtures of the primary materials available to the SFF machine. Design tools based u p on distance functions are also introduced, such as the speci cation of composition as a function of the distance from the surface of a part. Finally, the role of design rules restricting maximum and minimum concentrations is discussed.

Biomaterials, 2005

The component materials of controlled-release drug delivery systems are often selected based on t... more The component materials of controlled-release drug delivery systems are often selected based on their degradation rates. The release time of a drug from a system will strongly depend on the degradation rates of the component polymers. We have observed that some poly(lactic-co-glycolic acid) polymers (PLGA) exhibit degradation rates that depend on the size of the polymer object and the temperature

Journal of Materials Research, 1994

Heteroepitxial growth of Ba2YCu3O7-x (BYC) thin films prepared by postdeposition annealing on (00... more Heteroepitxial growth of Ba2YCu3O7-x (BYC) thin films prepared by postdeposition annealing on (001) LaAlO3 was characterised by TEM and XRD studies of specimens rapidly cooled from various points in the growth heat treatment. Heteroepitaxial nucleation ...

Chronopharmaceutics, 2009

Page 1. CHAPTER 9 CONTROLLED RELEASE MICROCHIPS KAREN DANIEL, HONG LINH HO DUC, MICHAEL CIMA, and... more Page 1. CHAPTER 9 CONTROLLED RELEASE MICROCHIPS KAREN DANIEL, HONG LINH HO DUC, MICHAEL CIMA, and ROBERT LANGER ''Our brains are seventy-year clocks. The Angel of Life winds them up once for ...

Science Translational Medicine, 2012

Limited treatment options exist for patients who suffer from a painful bladder condition known as... more Limited treatment options exist for patients who suffer from a painful bladder condition known as interstitial cystitis/bladder pain syndrome (IC/BPS). Whether given systemically (orally) or by short-duration (1 to 2 hours) exposure via intravesical instillation, therapeutic agents have exhibited poor efficacy because their concentrations in the bladder are low. A previous attempt to develop a drug delivery device for use in the bladder was unsuccessful, likely as a result of poor tolerability. A continuous lidocaine-releasing intravesical system (LiRIS) was designed to be retained in the bladder and release therapeutic amounts of the drug into urine over a period of 2 weeks. The device was tested in healthy volunteers and IC/BPS patients and was found to be well tolerated in both subject groups because of its small size and freedom of movement within the bladder. The 16 women with IC/BPS who were enrolled in the study met the National Institute of Diabetes and Digestive and Kidney Diseases criteria for bladder hemorrhages or Hunner's lesions. Subjects received either LiRIS 200 mg or LiRIS 650 mg for 2 weeks. Safety, efficacy, cystoscopic appearance of the bladder, and limited pharmacokinetic data were collected. Both doses were well tolerated, and clinically meaningful reductions were seen in pain, urgency, voiding frequency, and disease questionnaires. Cystoscopic examinations showed improvement on day 14 (day of removal) compared with day 1, including resolution of Hunner's lesions in five of six subjects with baseline lesions. Global response assessment showed an overall responder rate of 64% at day 14 and a sustained overall responder rate of 64% 2 weeks later. Extended follow-up suggests that the reduction in pain was maintained for several months after the device was removed.

Proceedings of the IEEE, 2004

MEMS devices are manufactured using similar microfabrication techniques as those used to create i... more MEMS devices are manufactured using similar microfabrication techniques as those used to create integrated circuits. They often, however, have moving components that allow physical or analytical functions to be performed by the device. Although MEMS can be aseptically fabricated and hermetically sealed, biocompatibility of the component materials is a key issue for MEMS used in vivo. Interest in MEMS for biological applications (BioMEMS) is growing rapidly, with opportunities in areas such as biosensors, pacemakers, immunoisolation capsules, and drug delivery. The key to many of these applications lies in the leveraging of features unique to MEMS (for example, analyte sensitivity, electrical responsiveness, temporal control, and feature sizes similar to cells and organelles) for maximum impact. In this paper, we focus on how the biological integration of MEMS and other implantable devices can be improved through the application of microfabrication technology and concepts. Innovative approaches for improved physical and chemical integration of systems with the body are reviewed. An untapped potential for MEMS may lie in the area of nervous and endocrine system actuation, whereby the ability of MEMS to deliver potent drugs or hormones, combined with their precise temporal control, may provide new treatments for disorders of these systems.

Polymer Engineering & Science, 2000

Three Dimensional Printing is a desktop manufacturing process in which powdered materials are dep... more Three Dimensional Printing is a desktop manufacturing process in which powdered materials are deposited in layers and selectively joined with binder from an ink-jet style printhead. Unbound powder is removed upon process completion, leaving a three dimensional part. Stainless steel injection molding inserts have been created from metal powder with the 3DP process.

Physica C: Superconductivity, 2004

Precursor films prepared by metal organic deposition are shown to be much richer in fluorine than... more Precursor films prepared by metal organic deposition are shown to be much richer in fluorine than previously suspected. The ratio of fluorine to barium is 2.7 when the film is prepared at 400°C and decreases with increasing temperature. That is, the films contain more fluorine than can be explained by only barium fluoride being present. The remaining F/Ba ratio trajectory of MOD decreases from 2.7 to about 1.5 without the formation of detectable Ba 2 YCu 3 O 6:5 (YBCO). The trajectory is also shown to include compositions known to contain low melting liquids. These observations show that YBCO formation from MOD-derived precursor occurs in multiple steps: (1) decomposition of YF 3 , (2) decomposition of BaF 2 without YBCO nucleation, (3) formation of YBCO via liquid phase. This means small amount of oxyfluoride melt is present in the film during the conversion to YBCO. Thicker films have a larger F/Ba ratio at any given temperature which possibly leads to more melt. The melt may contribute to the densification and the epitaxial growth of YBCO. It may also, however, cause reaction with substrate and/or buffer layer.

Pharmaceutical Research, 2006

Micro-and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become ... more Micro-and nano-electromechanical systems (MEMS and NEMS)-based drug delivery devices have become commercially-feasible due to converging technologies and regulatory accommodation. The FDA Office of Combination Products coordinates review of innovative medical therapies that join elements from multiple established categories: drugs, devices, and biologics. Combination products constructed using MEMS or NEMS technology offer revolutionary opportunities to address unmet medical needs related to dosing. These products have the potential to completely control drug release, meeting requirements for on-demand pulsatile or adjustable continuous administration for extended periods. MEMS or NEMS technologies, materials science, data management, and biological science have all significantly developed in recent years, providing a multidisciplinary foundation for developing integrated therapeutic systems. If small-scale biosensor and drug reservoir units are combined and implanted, a wireless integrated system can regulate drug release, receive sensor feedback, and transmit updates. For example, an Bartificial pancreas^implementation of an integrated therapeutic system would improve diabetes management. The tools of microfabrication technology, information science, and systems biology are being combined to design increasingly sophisticated drug delivery systems that promise to significantly improve medical care.

Pharmaceutical compounds are molecular solids that frequently exhibit polymorphism of crystal for... more Pharmaceutical compounds are molecular solids that frequently exhibit polymorphism of crystal form. One high profile case of polymorphism was ritonavir, a peptidomimetic drug used to treat HIV-1 infection and introduced in 1996. In 1998, a lower energy, more stable polymorph (form II) appeared, causing slowed dissolution of the marketed dosage form and compromising the oral bioavailability of the drug. This event forced the removal of the oral capsule formulation from the market. We have carried out high-throughput crystallization experiments to comprehensively explore ritonavir form diversity. A total of five forms were found: both known forms and three previously unknown forms. The novel forms include a metastable polymorph, a hydrate phase, and a formamide solvate. The solvate was converted to form I via the hydrate phase by using a simple washing procedure, providing an unusual route to prepare the form I ''disappearing polymorph'' [Dunitz, J. D. & Bernstein, J. (1995) Acc. Chem. Res. 28, 193-200].

Journal of Materials Research - J MATER RES, 1998

ABSTRACT A new quenching technique was used for detailed microstructural examination of quenched ... more ABSTRACT A new quenching technique was used for detailed microstructural examination of quenched YBa2Cu3O6+δ/liquid interfaces. The examination revealed that the growth rate and the amount of excess Y2BaCuO5 (211) had a strong influence on the growth morphology of YBa2Cu3O6+δ (123). The maximum growth rate at which single crystal growth could be obtained increased from 1 μm/s to 1.5 μm/s as excess 211 content increased from 0 to 20 wt. %. It then decreased to 1 μm/s as excess 211 increased to 40 wt. %. Dendritic growth with distinguishable secondary arms occurred for stoichiometric 123 samples in the regime of cellular/dendritic growth. A highly curved 123 envelope was formed on 211 particles located at the 123 growth interface for stoichiometric 123 samples in the regime of single crystal growth. The microscopic 123 growth interface became flat as excess 211 content increased to 20 wt. %. The engulfment of 211 particles into 123 matrix is discussed based on detailed microstructural examination. It is found that the formation of a small highly curved 123 envelope on 211 particles for stoichiometric 123 samples is due to the large 211 particle spacing.

Nature Materials, 2003

nature materials | VOL 2 | NOVEMBER 2003 | www.nature.com/naturematerials 767 T he method by whic... more nature materials | VOL 2 | NOVEMBER 2003 | www.nature.com/naturematerials 767 T he method by which a drug is delivered can have a significant effect on the drug's therapeutic efficacy 1 . Conventional drug delivery systems such as implants and some oral delivery systems typically produce a sharp initial increase in drug concentration to a peak above the therapeutic range, followed by a fast decrease in concentration to a level below the therapeutic range. The time spent in the optimum concentration range for therapeutic effect is therefore short 2 . Initial concentration peaks can pose a serious risk of toxicity and related complications for potent drugs. Additionally, accurate and repeatable dosing of medication to patients may be difficult to achieve because of patient non-compliance. The field of controlled-release drug delivery therefore initially focused on achieving a constant release of drug over long periods with minimal influence by outside factors. However,for certain molecules or drugs,sustained or continuous release is not optimal. For example, insulin 3 and hormones of the anterior pituitary gland such as growth hormone and gonadotropin-releasing hormone (GnRH) are secreted by the human body in a pulsatile fashion 4 . It is desirable for therapies that treat deficiencies or disorders of these molecules to mimic the pulsatile fashion in which the molecules are naturally released from the body. Similarly, for multi-dose vaccines, repeated delivery of the antigen is desired for optimal antibody response.

Materials Science and Engineering: A, 2001

Carbon performs have been fabricated using the three-dimensional printing (3DP™) process for reac... more Carbon performs have been fabricated using the three-dimensional printing (3DP™) process for reaction-infiltrated SiC-Si composites. Starting with glassy carbon powders of 45 -105 mm sizes, the preform was produced by printing acetone-based furfuryl resin binder. The bulk density and open porosity of the resulting preform was 0.6 g cm − 3 and 48%, respectively. The binder printing conditions during preform fabrication mostly determined the preform microstructure. Pressureless reactive infiltration of such preforms at 1450°C in nitrogen atmosphere formed a SiC -Si composite with a coarse-SiC grain structure. Some residual carbon remained inside the SiC grains in this reaction bonded SiC -C due to sluggish reactivity of the larger carbon powder particles. Relatively complex-shaped carbon preforms with overhang, undercut, and inner channel structures were produced, demonstrating the capability of the 3DP process. A functionally graded SiC -Si composite was also fabricated, by varying carbon-yielding binder dosage during the preform fabrication, in order to control the spatial SiC concentration within the SiC-Si composite.

Langmuir, 2003

Undecanethiol (C11H23SH) and tri(ethylene glycol)-terminated undecanethiol (HO(C2H4O)3C11H22SH) s... more Undecanethiol (C11H23SH) and tri(ethylene glycol)-terminated undecanethiol (HO(C2H4O)3C11H22SH) self-assembled monolayers (SAMs) on clean gold surfaces were prepared and characterized. The SAMs were then immersed into either phosphate-buffered saline or calf serum. The SAM samples were investigated using several analytical techniques at numerous points over the next 35 days. Contact angles and current densities in voltammetry changed dramatically for the PBS samples over the time period, particularly after 21 days. Results indicate substantial loss of the integrity of the SAM. Similar alterations with time were observed for the calf serum samples in both contact angle and voltammetry measurements. X-ray photoelectron spectroscopy indicates that the likely origin is desorption of the alkanethiol moiety as evidenced by appreciable loss of the S 2p signal after 35 days.

Lab on a Chip, 2007

By combining the sensing capabilities of nanoscale magnetic relaxation switches (MRS) within mult... more By combining the sensing capabilities of nanoscale magnetic relaxation switches (MRS) within multi-reservoir structures, a potentially powerful implantable multiplexed sensor has been developed. MRS are magnetic nanoparticles that decrease the transverse relaxation time (T(2)) of water in the presence of an analyte. The switches encased in polydimethylsiloxane (PDMS) devices with polycarbonate membranes (10 nm pores) have demonstrated in vitro sensing of the beta subunit of human chorionic gonadotrophin (hCG-beta), which is elevated in testicular and ovarian cancer. Devices showed transverse relaxation time (T(2)) shortening by magnetic resonance imaging (MRI) when incubated in analyte solutions of 0.5 to 5 microg hCG-beta mL(-1). The decrease in T(2) was between 9% and 27% (compared to control devices) after approximately 28 h. This prototype device is an important first step in developing an implantable sensor for detecting soluble cancer biomarkers in vivo.