公开(公告)号：WO2012088149A2

公开(公告)日：2012-06-28

申请号：PCT/US2011/066239

申请日：2011-12-20

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  ARENA, Christopher B. ,  DAVALOS, Rafael V. ,  SANO, Michael B.

Inventor： ARENA, Christopher B. ,  DAVALOS, Rafael V. ,  SANO, Michael B.

IPC: A61N1/06 ,  A61N1/05 ,  A61N1/18 ,  A61N5/00

CPC classification number: A61B18/14 ,  A61B2018/0016 ,  A61B2018/00577 ,  A61B2018/00613 ,  A61B2018/00761 ,  A61B2018/00767 ,  A61N1/327

Abstract: The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.

Abstract translation: 本发明涉及疾病和病症的生物医学工程和医学治疗领域。 提供了体内治疗细胞增殖性疾病的方法，装置和系统。 在实施例中，这些方法包括输送高频脉冲串的双极脉冲以实现所需的细胞死亡模式。 更具体地，本发明的实施例涉及使用高频双极电脉冲来破坏包括肿瘤组织的异常细胞的装置和方法，其具有微秒级的微秒级和单极性的持续时间，微秒至纳秒级 。 在实施方案中，所述方法依赖于常规电穿孔辅助药物或不可逆电穿孔以在治疗的肿瘤中引起细胞死亡。 本发明可用于治疗诸如脑肿瘤的实体瘤。

公开(公告)号：WO2010141027A1

公开(公告)日：2010-12-09

申请号：PCT/US2009/046407

申请日：2009-06-05

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  GATENHOLM, Paul ,  DAVALOS, Rafael, V. ,  SANO, Michael, B.

Inventor： GATENHOLM, Paul ,  DAVALOS, Rafael, V. ,  SANO, Michael, B.

IPC: A61L27/36 ,  A61F2/28

CPC classification number: A61L27/3804 ,  A61L27/36 ,  A61L27/3895 ,  B33Y80/00 ,  C12M21/08 ,  C12M25/14

Abstract: The precise application of an electromagnetic field controls cell motion to guide extrusion and deposition of biopolymers produced by the cells. This controlled biofabrication process is used to fabricate two- and three-dimensional networks of biocompatible nanofibrils (such as cellulose) for use as biomaterials, tissue scaffolds to be used in regenerative medicine, coatings for biomedical devices, and other health care products.

Abstract translation: 电磁场的精确应用控制细胞运动以引导由细胞产生的生物聚合物的挤出和沉积。 这种受控的生物制造过程用于制造用作生物材料的生物相容纳米原纤维（例如纤维素）的二维和三维网络，用于再生医学的组织支架，用于生物医学装置的涂层和其他保健产品。

公开(公告)号：WO2012088149A3

公开(公告)日：2012-11-01

申请号：PCT/US2011066239

申请日：2011-12-20

Applicant: VIRGINIA TECH INTELL PROP ,  ARENA CHRISTOPHER B ,  DAVALOS RAFAEL V ,  SANO MICHAEL B

Inventor： ARENA CHRISTOPHER B ,  DAVALOS RAFAEL V ,  SANO MICHAEL B

IPC: A61N1/06 ,  A61N1/05 ,  A61N1/18 ,  A61N5/00

CPC classification number: A61B18/14 ,  A61B2018/0016 ,  A61B2018/00577 ,  A61B2018/00613 ,  A61B2018/00761 ,  A61B2018/00767 ,  A61N1/327

Abstract: The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.

Abstract translation: 本发明涉及疾病和病症的生物医学工程和医学治疗领域。 提供了用于体内治疗细胞增殖性病症的方法，装置和系统。 在实施方案中，所述方法包括递送双极性脉冲的高频突发以实现期望的细胞死亡模式。 更具体地说，本发明的实施例涉及使用高频双极电脉冲破坏异常细胞（包括肿瘤组织）的装置和方法，所述高频双极电脉冲具有微秒至单位极性的持续时间的微秒至纳秒级的脉冲宽度 。 在实施方案中，所述方法依赖于用辅助药物进行的常规电穿孔或不可逆的电穿孔以在治疗的肿瘤中引起细胞死亡。 本发明可以用于治疗实体瘤，例如脑肿瘤。

公开(公告)号：WO2012048230A3

公开(公告)日：2012-07-12

申请号：PCT/US2011055381

申请日：2011-10-07

Applicant: VIRGINIA TECH INTELL PROP ,  SANO MICHAEL B ,  CALDWELL JOHN L ,  DAVALOS RAFAEL V

Inventor： SANO MICHAEL B ,  CALDWELL JOHN L ,  DAVALOS RAFAEL V

IPC: G01N35/08 ,  G01N33/483 ,  G01N35/00

CPC classification number: B03C5/005 ,  B03C5/026 ,  B03C2201/26

Abstract: Devices and methods for performing dielectrophoresis are described. The devices contain a sample channel which is separated by physical barriers from electrode channels which receive electrodes. The devices and methods may be used for the separation and analysis of particles in solution, including the separation and isolation of cells of a specific type. As the electrodes do not make contact with the sample, electrode fouling is avoided and sample integrity is better maintained.

Abstract translation: 描述了用于执行介电泳的装置和方法。 这些器件包含一个样品通道，通过物理屏障与接收电极的电极通道分开。 该装置和方法可用于分离和分析溶液中的颗粒，包括分离和分离特定类型的细胞。 由于电极不与样品接触，因此避免了电极污垢，并且样品完整性得到了更好的保持。

公开(公告)号：WO2012048230A2

公开(公告)日：2012-04-12

申请号：PCT/US2011/055381

申请日：2011-10-07

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  SANO, Michael, B. ,  CALDWELL, John, L. ,  DAVALOS, Rafael, V.

Inventor： SANO, Michael, B. ,  CALDWELL, John, L. ,  DAVALOS, Rafael, V.

IPC: G01N35/08 ,  G01N35/00 ,  G01N33/483

CPC classification number: B03C5/005 ,  B03C5/026 ,  B03C2201/26

Abstract: Devices and methods for performing dielectrophoresis are described. The devices contain a sample channel which is separated by physical barriers from electrode channels which receive electrodes. The devices and methods may be used for the separation and analysis of particles in solution, including the separation and isolation of cells of a specific type. As the electrodes do not make contact with the sample, electrode fouling is avoided and sample integrity is better maintained.

Abstract translation: 描述了用于进行介电电泳的装置和方法。 这些器件包含一个样品通道，该通道由接收电极的电极通道的物理屏障分开。 该装置和方法可用于分离和分析溶液中的颗粒，包括分离和分离特定类型的细胞。 由于电极不与样品接触，因此避免了电极污垢，维持样品的完整性。

公开(公告)号：WO2011038373A3

公开(公告)日：2011-03-31

申请号：PCT/US2010/050460

申请日：2010-09-28

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  GATENHOLM, Paul ,  BACKDAHL, Henrik ,  TZAVARAS, Theodore, Jon ,  DAVALOS, Rafael, V. ,  SANO, Michael, B.

Inventor： GATENHOLM, Paul ,  BACKDAHL, Henrik ,  TZAVARAS, Theodore, Jon ,  DAVALOS, Rafael, V. ,  SANO, Michael, B.

IPC: A61L27/40 ,  A61L27/44 ,  A61L27/38 ,  C12N1/20 ,  C12N1/22 ,  C12R1/02

Abstract: A novel BC fermentation technique for controlling 3D shape, thickness and architecture of the entangled cellulose nano-fibhl network is presented. The resultant nano-cellulose based structures are useful as biomedical implants and devices, are useful for tissue engineering and regenerative medicine, and for health care products. More particularly, embodiments of the present invention relate to systems and methods for the production and control of 3-D architecture and morphology of nano-cellulose biomaterials produced by bacteria using any biofabrication process, including the novel 3-D Biophnting processes disclosed. Representative processes according to the invention involve control of the rate of production of biomatehal by bacteria achieved by meticulous control of the addition of fermentation media using a microfluidic system. In exemplary embodiments, the bacteria gradually grew up along the printed alginate structure that had been placed into the culture, incorporating it. After culture, the printed alginate structure was successfully removed revealing porosity where the alginate had been placed. Porosity and interconnectivity of pores in the resultant 3-D architecture can be achieved by porogen introduction using, e.g., ink-jet printer technology.

Abstract translation: 介绍了用于控制缠结的纤维素纳米纤维网络的三维形状，厚度和结构的新型BC发酵技术。 得到的基于纳米纤维素的结构可用作生物医学植入物和装置，可用于组织工程和再生医学以及保健产品。 更具体地说，本发明的实施方案涉及用于生产和控制由细菌使用任何生物加工方法产生的纳米纤维素生物材料的3-D结构和形态的系统和方法，所述生物加工方法包括所公开的新型3-D Biophnting方法。 根据本发明的代表性方法涉及通过使用微流体系统细致控制发酵培养基的添加来实现细菌对生物气体生产速率的控制。 在示例性实施方案中，细菌沿着已经放入培养物中的印刷的藻酸盐结构逐渐生长，并入其中。 培养后，印刷的藻酸盐结构被成功去除，显示出已经放置了藻酸盐的孔隙。 通过使用例如喷墨打印机技术导入致孔剂可以实现所得3-D架构中的孔隙的孔隙率和互连性。

公开(公告)号：WO2011038373A2

公开(公告)日：2011-03-31

申请号：PCT/US2010050460

申请日：2010-09-28

Applicant: VIRGINIA TECH INTELL PROP ,  GATENHOLM PAUL ,  BACKDAHL HENRIK ,  TZAVARAS THEODORE JON ,  DAVALOS RAFAEL V ,  SANO MICHAEL B

Inventor： GATENHOLM PAUL ,  BACKDAHL HENRIK ,  TZAVARAS THEODORE JON ,  DAVALOS RAFAEL V ,  SANO MICHAEL B

IPC: A61L27/40 ,  A61L27/38 ,  A61L27/44 ,  C12N1/20 ,  C12N1/22 ,  C12R1/02

CPC classification number: C08B1/00 ,  A61L27/20 ,  A61L27/38 ,  A61L27/56 ,  A61L2400/12 ,  C12N5/0062 ,  C12N11/12 ,  C12N2533/78 ,  C12P19/04 ,  C08L1/02

Abstract: A novel BC fermentation technique for controlling 3D shape, thickness and architecture of the entangled cellulose nano-fibhl network is presented. The resultant nano-cellulose based structures are useful as biomedical implants and devices, are useful for tissue engineering and regenerative medicine, and for health care products. More particularly, embodiments of the present invention relate to systems and methods for the production and control of 3-D architecture and morphology of nano-cellulose biomaterials produced by bacteria using any biofabrication process, including the novel 3-D Biophnting processes disclosed. Representative processes according to the invention involve control of the rate of production of biomatehal by bacteria achieved by meticulous control of the addition of fermentation media using a microfluidic system. In exemplary embodiments, the bacteria gradually grew up along the printed alginate structure that had been placed into the culture, incorporating it. After culture, the printed alginate structure was successfully removed revealing porosity where the alginate had been placed. Porosity and interconnectivity of pores in the resultant 3-D architecture can be achieved by porogen introduction using, e.g., ink-jet printer technology.

Abstract translation: 提出了一种控制缠结纤维素纳米纤维网络的三维形状，厚度和结构的新型BC发酵技术。 得到的基于纳米纤维素的结构可用作生物医学植入物和装置，可用于组织工程和再生医学以及保健产品。 更具体地说，本发明的实施方案涉及用于生产和控制由细菌使用任何生物加工方法产生的纳米纤维素生物材料的3-D结构和形态的系统和方法，所述生物加工方法包括所公开的新型3-D Biophnting方法。 根据本发明的代表性方法涉及通过使用微流体系统细致控制发酵培养基的添加来实现细菌对生物气体生产速率的控制。 在示例性实施方案中，细菌沿着已经放入培养物中的印刷的藻酸盐结构逐渐生长，并入其中。 培养后，印刷的藻酸盐结构被成功去除，显示出已经放置了藻酸盐的孔隙。 通过使用例如喷墨打印机技术引入致孔剂可以实现所得3-D结构中孔的孔隙率和相互连接性。

公开(公告)号：WO2015175570A1

公开(公告)日：2015-11-19

申请号：PCT/US2015/030429

申请日：2015-05-12

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  SANO, Michael, B. ,  ARENA, Christopher, B. ,  VERBRIDGE, Scott, S. ,  DAVALOS, Rafael, V.

Inventor： SANO, Michael, B. ,  ARENA, Christopher, B. ,  VERBRIDGE, Scott, S. ,  DAVALOS, Rafael, V.

IPC: C12N5/00 ,  C12N5/02

CPC classification number: A61N1/327 ,  A61B18/1206 ,  A61B18/1477 ,  A61B90/37 ,  A61B2017/00172 ,  A61B2018/00577 ,  A61B2018/126 ,  A61B2018/143 ,  A61N1/06 ,  A61N1/08 ,  A61N1/40

Abstract: A system and method for selectively treating aberrant cells such as cancer cells through administration of a train of electrical pulses is described. The pulse length and delay between successive pulses is optimized to produce effects on intracellular membrane potentials. Therapies based on the system and method produce two treatment zones: an ablation zone surrounding the electrodes within which aberrant cells are non- selectively killed and a selective treatment zone surrounding the ablation zone within which target cells are selectively killed through effects on intracellular membrane potentials. As a result, infiltrating tumor cells within a tumor margin can be effectively treated while sparing healthy tissue. The system and method are useful for treating various cancers in which solid tumors form and have a chance of recurrence from microscopic disease surrounding the tumor.

Abstract translation: 描述了通过施加一系列电脉冲来选择性地治疗异常细胞例如癌细胞的系统和方法。 优化连续脉冲之间的脉冲长度和延迟，以产生对细胞内膜电位的影响。 基于系统和方法的治疗产生两个治疗区：围绕电极的消融区，其中异常细胞被非选择性杀死，围绕消融区的选择性治疗区，通过对细胞内膜电位的影响，靶细胞被选择性地杀死。 因此，可以有效地治疗肿瘤边缘内的浸润肿瘤细胞，同时节省健康组织。 该系统和方法可用于治疗各种癌症，其中实体瘤形成并有机会从肿瘤周围的微观疾病复发。

公开(公告)号：WO2012088149A4

公开(公告)日：2013-01-17

申请号：PCT/US2011066239

申请日：2011-12-20

Applicant: VIRGINIA TECH INTELL PROP ,  ARENA CHRISTOPHER B ,  DAVALOS RAFAEL V ,  SANO MICHAEL B

Inventor： ARENA CHRISTOPHER B ,  DAVALOS RAFAEL V ,  SANO MICHAEL B

IPC: A61N1/06 ,  A61N1/05 ,  A61N1/18 ,  A61N5/00

CPC classification number: A61B18/14 ,  A61B2018/0016 ,  A61B2018/00577 ,  A61B2018/00613 ,  A61B2018/00761 ,  A61B2018/00767 ,  A61N1/327

Abstract: The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.

Abstract translation: 本发明涉及疾病和病症的生物医学工程和医学治疗领域。 提供了体内治疗细胞增殖性疾病的方法，装置和系统。 在实施例中，这些方法包括输送高频脉冲串的双极脉冲以实现所需的细胞死亡模式。 更具体地，本发明的实施例涉及使用高频双极电脉冲来破坏包括肿瘤组织的异常细胞的装置和方法，其具有微秒级的微秒级和单极性的持续时间，微秒至纳秒级 。 在实施方案中，所述方法依赖于常规电穿孔辅助药物或不可逆电穿孔以在治疗的肿瘤中引起细胞死亡。 本发明可用于治疗诸如脑肿瘤的实体瘤。