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An arched micro-injector (ARCMI) for innocuous subretinal injection.

You YS, Lee CY, Li C, Lee SH, Kim K, Jung H - PLoS ONE (2014)

Bottom Line: ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating.These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo.We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

View Article: PubMed Central - PubMed

Affiliation: Nune Eye Hospital, Seoul, Republic of Korea.

ABSTRACT
Several critical ocular diseases that can lead to blindness are due to retinal disorders. Subretinal drug delivery has been developed recently for the treatment of retinal disorders such as hemorrhage because of the specific ocular structure, namely, the blood retinal barrier (BRB). In the present study, we developed an Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal tissue damage. ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating. In order to achieve minimal retinal tissue damage, ARCMIs were fabricated with specific features such as a 0.15 mm(-1) curvature, 45° tip bevel, 5 mm length, inner diameter of 40 µm, and an outer diameter of 100 µm. These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

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Illustration of the fabrication method for the arched micro-injector (ARCMI).(A) A straight SU-8 mold was formed at the end of blunt hollow metallic cannula (e.g., hypodermic needle) by reverse drawing lithography. (B) A flow of controlled air from a centrifugal fan produced the curved structure on the tip of the SU-8 mold of the ARCMI. (C) Hollow metallic walls on the mold surface were adopted by nickel sputtering and electroplating. (D) A hollow beveled tip was fabricated via tip polishing and removal of the SU-8 mold. (E) The hollow metallic structure of ARCMI formed after washing the mold.
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pone-0104145-g002: Illustration of the fabrication method for the arched micro-injector (ARCMI).(A) A straight SU-8 mold was formed at the end of blunt hollow metallic cannula (e.g., hypodermic needle) by reverse drawing lithography. (B) A flow of controlled air from a centrifugal fan produced the curved structure on the tip of the SU-8 mold of the ARCMI. (C) Hollow metallic walls on the mold surface were adopted by nickel sputtering and electroplating. (D) A hollow beveled tip was fabricated via tip polishing and removal of the SU-8 mold. (E) The hollow metallic structure of ARCMI formed after washing the mold.

Mentions: As shown in Figure 2, each ARCMI was fabricated by modified reverse drawing lithography and a controlled air flow consisting of three major steps: solid micro mold fabrication by reverse drawing lithography, curvature adaptation on a solid micro mold, and formation of a hollow metallic structure formation. Reverse drawing lithography was performed by vertical drawing of heated SU-8 2050 viscoelastic material (Microchem, USA) using a 27 G hypodermic needle (Jung lim, Republic of Korea).[12] The drawing machine was created in house and was equipped with drawing (pulling) parts and heating parts. The drawing parts were located on the top of the drawing machine to allow for a vertical pulling motion for the fabrication of micromechanical mold from viscoelastic materials. The heating parts consisted of a round shaped metal plate to regulate temperature. Before drawing the solid micro mold, a 27 G hypodermic needle 1.5 inches in length with an outer diameter of 300 µm was adjusted on the drawing system. SU-8 2050 was coated on a 6-inch wafer to a thickness of 160 µm using a spin-coater (YS-100D, Republic of Korea) at a speed of 1000 rpm. The temperature was increased up to 150°C for 10 min, which was followed by solidification of SU-8 2050 at room temperature. Drawing was conducted vertically over a temperature range of 75 to 85°C at a rate of 1 mm/s to produce a solid mold diameter of 40±10 µm. The time required to raise the viscoelastic materials including SU-8 was such that it was directly associated with the length of fabricated solid molds. Specifically, linear solid micro molds with lengths of 5 and 10 mm were generated by pulling for 5 and 10 seconds, respectively.


An arched micro-injector (ARCMI) for innocuous subretinal injection.

You YS, Lee CY, Li C, Lee SH, Kim K, Jung H - PLoS ONE (2014)

Illustration of the fabrication method for the arched micro-injector (ARCMI).(A) A straight SU-8 mold was formed at the end of blunt hollow metallic cannula (e.g., hypodermic needle) by reverse drawing lithography. (B) A flow of controlled air from a centrifugal fan produced the curved structure on the tip of the SU-8 mold of the ARCMI. (C) Hollow metallic walls on the mold surface were adopted by nickel sputtering and electroplating. (D) A hollow beveled tip was fabricated via tip polishing and removal of the SU-8 mold. (E) The hollow metallic structure of ARCMI formed after washing the mold.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128757&req=5

pone-0104145-g002: Illustration of the fabrication method for the arched micro-injector (ARCMI).(A) A straight SU-8 mold was formed at the end of blunt hollow metallic cannula (e.g., hypodermic needle) by reverse drawing lithography. (B) A flow of controlled air from a centrifugal fan produced the curved structure on the tip of the SU-8 mold of the ARCMI. (C) Hollow metallic walls on the mold surface were adopted by nickel sputtering and electroplating. (D) A hollow beveled tip was fabricated via tip polishing and removal of the SU-8 mold. (E) The hollow metallic structure of ARCMI formed after washing the mold.
Mentions: As shown in Figure 2, each ARCMI was fabricated by modified reverse drawing lithography and a controlled air flow consisting of three major steps: solid micro mold fabrication by reverse drawing lithography, curvature adaptation on a solid micro mold, and formation of a hollow metallic structure formation. Reverse drawing lithography was performed by vertical drawing of heated SU-8 2050 viscoelastic material (Microchem, USA) using a 27 G hypodermic needle (Jung lim, Republic of Korea).[12] The drawing machine was created in house and was equipped with drawing (pulling) parts and heating parts. The drawing parts were located on the top of the drawing machine to allow for a vertical pulling motion for the fabrication of micromechanical mold from viscoelastic materials. The heating parts consisted of a round shaped metal plate to regulate temperature. Before drawing the solid micro mold, a 27 G hypodermic needle 1.5 inches in length with an outer diameter of 300 µm was adjusted on the drawing system. SU-8 2050 was coated on a 6-inch wafer to a thickness of 160 µm using a spin-coater (YS-100D, Republic of Korea) at a speed of 1000 rpm. The temperature was increased up to 150°C for 10 min, which was followed by solidification of SU-8 2050 at room temperature. Drawing was conducted vertically over a temperature range of 75 to 85°C at a rate of 1 mm/s to produce a solid mold diameter of 40±10 µm. The time required to raise the viscoelastic materials including SU-8 was such that it was directly associated with the length of fabricated solid molds. Specifically, linear solid micro molds with lengths of 5 and 10 mm were generated by pulling for 5 and 10 seconds, respectively.

Bottom Line: ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating.These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo.We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

View Article: PubMed Central - PubMed

Affiliation: Nune Eye Hospital, Seoul, Republic of Korea.

ABSTRACT
Several critical ocular diseases that can lead to blindness are due to retinal disorders. Subretinal drug delivery has been developed recently for the treatment of retinal disorders such as hemorrhage because of the specific ocular structure, namely, the blood retinal barrier (BRB). In the present study, we developed an Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal tissue damage. ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating. In order to achieve minimal retinal tissue damage, ARCMIs were fabricated with specific features such as a 0.15 mm(-1) curvature, 45° tip bevel, 5 mm length, inner diameter of 40 µm, and an outer diameter of 100 µm. These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage.

Show MeSH
Related in: MedlinePlus