Abstract: A 3D printed biocompatible drug delivery device is provided having a fluid delivery channel distinguishing three segments and a receiving chamber with an array of microneedles. The three segments of the delivery channel are stagnation zones before a drug is extruded and whereby an inverted funnel provides an increasing extrusion surface servicing the drug to the array of microneedles. The design of the device with its flow-related components circumvents the challenge of colloidal stability associated with multi-phase formulations leading to nozzle blockage. Qualitative screening cytotoxicity tests pre and post-extrusion through the drug delivery device using mammalian cells rule out cytotoxicity and outline equivalent viability to control treatments. The biocompatibility results suggest that the fluid delivery design, the photoresin selected as well as the fabrication and sterilization may be extended over a range of regenerative medicine and drug delivery applications.

Abstract: A 3D printed biocompatible drug delivery device is provided having a fluid delivery channel distinguishing three segments and a receiving chamber with an array of microneedles. The three segments of the delivery channel are stagnation zones before a drug is extruded and whereby an inverted funnel provides an increasing extrusion surface servicing the drug to the array of microneedles. The design of the device with its flow-related components circumvents the challenge of colloidal stability associated with multi-phase formulations leading to nozzle blockage. Qualitative screening cytotoxicity tests pre and post-extrusion through the drug delivery device using mammalian cells rule out cytotoxicity and outline equivalent viability to control treatments. The biocompatibility results suggest that the fluid delivery design, the photoresin selected as well as the fabrication and sterilization may be extended over a range of regenerative medicine and drug delivery applications.

Abstract: Methods are disclosed for synthesizing a plurality of compounds on the surface of supports. The synthesis comprises a series of cycles of steps in which reagents for conducting the synthesis are deposited on the surface of the support to form the chemical compounds. At least one physical parameter of the deposition varies between cycles The method comprises conducting the synthesis in at least two sets of cycles, arbitrarily designated as a first set and a second set. Each cycle comprises at least one step of depositing reagents on a surface by means of droplet dispensing elements that traverse the surface of the support. At least one, and desirably all, of the following deposition parameters are employed as indicated: The number of times of repetition for a step of depositing reagents in at least one cycle of the second set is less than the number of times of repetition for a corresponding step in at least one cycle of the first set.

Abstract: Methods and apparatus are disclosed for synthesizing a plurality of compounds such as biopolymers on the surface of supports. The synthesis comprises a plurality of steps in which reagents for conducting the synthesis are deposited on the surface of the support to form precursors of the chemical compounds and, ultimately, the chemical compounds themselves. An error in the deposition may occur in one or more of the plurality of steps. A reagent for forming the chemical compounds is deposited on the surface of the support. A determination is made as to whether an error occurred in the depositing of the reagent. If an error is detected, the support is treated to re-deposit at least some of those reagents that were not correctly deposited. In one approach the support is treated to stabilize precursors of the chemical compounds, the source of the error is corrected, and the reagent applied above is re-deposited on the surface.

Abstract: Methods and apparatus are disclosed for synthesizing a purality of compounds such as biopolymers on the surface of supports. The synthesis comprises a plurality of steps in which reagents for conducting the synthesis are deposited o the surface of the support to form precursors of the chemical compounds and, ultimately, the chemical compounds themselves. An error in the deposition may occur in one or more of the plurality of steps. A reagent for forming the chemical compounds is deposited on the surface of the support. A determination is made as to whether an error occurred in the depositing of the reagent. If an error is detected, the support is treated to re-deposit at least some of those reagents that were not correctly deposited. In one approach the support is treated to stabilize precursors of the chemical compounds, the source of the error is corrected, and the reagent applied above is re-deposited on the surface.

Abstract: Apparatus and methods are disclosed for forming a reaction chamber having relatively small volumes. An apparatus comprises two elements and a mechanism for introducing a gas to form a movable aerodynamic seal between the elements. In this manner a chamber having a controllable interior environment is formed. One of the elements may have at least a portion of a device for dispensing reagents sealingly affixed therein. The other element may be adapted for introduction of a support into the interior of the chamber formed by the top and the bottom element. The apparatus may be used in methods for synthesizing biopolymers on a support.

Abstract: Devices and methods are disclosed for synthesizing compounds on the surface of supports. The devices are flow devices, which include a housing comprising a housing chamber. The housing has an opening adapted for insertion of a support into the housing chamber. A sealing member is movably mounted in the housing chamber and adapted to engage the support to form a reagent chamber between a surface of the support and a surface of the sealing member. A mechanism is included for moving the sealing member within the housing chamber. The device has both an inlet and an outlet, which are both in fluid communication with the reagent chamber. In the methods of the invention a support is placed into a chamber of a device such as described above. The mechanism adapted to engage the support on a surface opposite the surface engaged by the sealing member is activated to urge the support toward the sealing member.

Abstract: Apparatus and methods are disclosed for forming a reaction chamber having relatively small volumes. An apparatus comprises two elements and a mechanism for introducing a gas to form a movable aerodynamic seal between the elements. In this manner a chamber having a controllable interior environment is formed. One of the elements may have at least a portion of a device for dispensing reagents sealingly affixed therein. The other element may be adapted for introduction of a support into the interior of the chamber formed by the top and the bottom element. The apparatus may be used in methods for synthesizing biopolymers on a support.

Abstract: Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Abstract: Devices and methods are disclosed for synthesizing compounds on the surface of supports. The devices are flow devices, which include a housing comprising a housing chamber. The housing has an opening adapted for insertion of a support into the housing chamber. A sealing member is movably mounted in the housing chamber and adapted to engage the support to form a reagent chamber between a surface of the support and a surface of the sealing member. A mechanism is included for moving the sealing member within the housing chamber. The device has both an inlet and an outlet, which are both in fluid communication with the reagent chamber. In the methods of the invention a support is placed into a chamber of a device such as described above. The mechanism adapted to engage the support on a surface opposite the surface engaged by the sealing member is activated to urge the support toward the sealing member.

Abstract: Methods and apparatus are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. The support is placed into a flow chamber, and a reagent is introduced into the flow chamber. The reagent is reactive with features on the surface of the support. During removal of the reagent from the flow chamber, the pressure in the chamber is maintained substantially atmospheric. In another embodiment the reagent is removed from the flow chamber under vacuum. In another embodiment the reagent is removed from the flow chamber by simultaneously venting and applying a vacuum to the flow chamber.

Abstract: Methods and apparatus are disclosed for synthesizing a plurality of compounds such as biopolymers on the surface of supports. The synthesis comprises a plurality of steps in which reagents for conducting the synthesis are deposited on the surface of the support to form precursors of the chemical compounds and, ultimately, the chemical compounds themselves. An error in the deposition may occur in one or more of the plurality of steps. In the method in accordance with the present invention, a reagent for forming the chemical compounds is deposited on the surface of the support. A determination is made as to whether an error occurred in the depositing of the reagent. If an error is detected, then, in accordance with the present invention, the support is treated to re-deposit at least some of those reagents that were not correctly deposited because of the error in the deposition step.

Abstract: Methods are disclosed for synthesizing a plurality of compounds on the surface of supports. The synthesis comprises a series of cycles of steps in which reagents for conducting the synthesis are deposited on the surface of the support to form the chemical compounds. At least one physical parameter of the deposition varies between cycles The method comprises conducting the synthesis in at least two sets of cycles, arbitrarily designated as a first set and a second set. Each cycle comprises at least one step of depositing reagents on a surface by means of droplet dispensing elements that traverse the surface of the support. At least one, and desirably all, of the following deposition parameters are employed as indicated: The number of times of repetition for a step of depositing reagents in at least one cycle of the second set is less than the number of times of repetition for a corresponding step in at least one cycle of the first set.

Abstract: Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Abstract: Apparatus and methods are disclosed for forming a reaction chamber having relatively small volumes. An apparatus comprises two elements and a mechanism for introducing a gas to form a movable aerodynamic seal between the elements. In this manner a chamber having a controllable interior environment is formed. One of the elements may have at least a portion of a device for dispensing reagents sealingly affixed therein. The other element may be adapted for introduction of a support into the interior of the chamber formed by the top and the bottom element. The apparatus may be used in methods for synthesizing biopolymers on a support.

Abstract: Devices and methods are disclosed for synthesizing compounds on the surface of supports. The devices are flow devices, which include a housing comprising a housing chamber. The housing has an opening adapted for insertion of a support into the housing chamber. A sealing member is movably mounted in the housing chamber and adapted to engage the support to form a reagent chamber between a surface of the support and a surface of the sealing member. A mechanism is included for moving the sealing member within the housing chamber. The device has both an inlet and an outlet, which are both in fluid communication with the reagent chamber. In the methods of the invention a support is placed into a chamber of a device such as described above. The mechanism adapted to engage the support on a surface opposite the surface engaged by the sealing member is activated to urge the support toward the sealing member.

Abstract: Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Abstract: A method of fabricating an array of multiple features of different chemical moieties on a substrate surface, and a method of using arrays so fabricated. The fabrication method includes determining an identity of a first direction across the substrate surface (such as a drawn direction) along which the substrate surface has a higher height uniformity than along a second direction across the substrate. Chemical moieties are placed on the substrate so as to provide features thereon along rows more closely aligned with the first direction than the second direction.