公开(公告)号：WO2013109832A1

公开(公告)日：2013-07-25

申请号：PCT/US2013/022066

申请日：2013-01-18

Applicant: IMRA AMERICA, INC.

Inventor： QIAN, Wei ,  CHE, Yong

IPC: B01J13/00 ,  A61K47/48 ,  B82Y5/00

CPC classification number: G01N21/64 ,  A61K47/6923 ,  B01J13/0034 ,  B01J13/0043 ,  B82Y30/00 ,  G01N21/554

Abstract: In the present invention, a method for determining the stability threshold amount of a stabilizer component for gold nanoparticles to prevent their aggregation in any electrolyte solution, is disclosed. The method permits for very low levels of stabilizer components to be used while still permitting conjugation with other functional ligands. The method comprises preparation of stable gold nanoparticles conjugated with different amount of stabilizing agents in deionized water first and then testing the stability of colloidal suspension of these gold nanoparticles in the presence of the electrolyte solution by monitoring the absorbance at 520 nm. The invention also comprises a method for fabrication of nanoconjugates comprising gold nanoparticles and only the stabilizer components or comprising gold nanoparticles, stabilizer components and functional ligands, which are stable in the presence of electrolytes.

Abstract translation: 在本发明中，公开了一种用于确定金纳米颗粒的稳定剂组分以防止其在任何电解质溶液中聚集的稳定剂阈值量的方法。 该方法允许使用非常低水平的稳定剂组分，同时仍允许与其它官能配体缀合。 该方法首先制备在去离子水中与不同量的稳定剂缀合的稳定金纳米颗粒，然后通过监测520nm处的吸光度，测定这些金纳米粒子在电解质溶液存在下的胶体悬浮液的稳定性。 本发明还包括一种制造纳米缀合物的方法，其包括金纳米颗粒并且仅包含稳定剂组分或包含在电解质存在下稳定的金纳米颗粒，稳定剂组分和官能配体。

公开(公告)号：WO2012118930A2

公开(公告)日：2012-09-07

申请号：PCT/US2012/027213

申请日：2012-03-01

Applicant: IMRA AMERICA, INC. ,  QIAN, Wei ,  MURAKAMI, Makoto ,  ICHIKAWA, Yuki ,  CHE, Yong

Inventor： QIAN, Wei ,  MURAKAMI, Makoto ,  ICHIKAWA, Yuki ,  CHE, Yong

IPC: A61K9/14 ,  G01N21/75 ,  A61K49/00 ,  A61K33/24 ,  C12Q1/00 ,  A61K39/395 ,  A61K38/43 ,  G01N33/53 ,  G01N21/64 ,  G01N21/62 ,  A61P35/00 ,  B82Y5/00 ,  B82Y15/00 ,  B82Y40/00

CPC classification number: A61K49/0002 ,  A61K9/0019 ,  A61K9/1688 ,  A61K41/0057 ,  A61K47/10 ,  B01J13/0034 ,  B01J13/0043 ,  B82Y5/00 ,  B82Y30/00 ,  B82Y40/00 ,  G01N21/64 ,  G01N21/658 ,  G01N33/531 ,  G01N33/54346 ,  G01N2021/3595

Abstract: In the present invention, a method of producing stable bare colloidal gold nanoparticles is disclosed. The nanoparticles can subsequently be subjected to partial or full surface modification. The method comprises preparation of colloidal gold nanoparticles in a liquid by employing a top-down nanofabrication method using bulk gold as a source material. The surface modification of these nanoparticles is carried out by adding one or multiple types of ligands each containing functional groups which exhibit affinity for gold nanoparticle surfaces to produce the conjugates. Because of the high efficiency and excellent stability of the nanoparticles produced by this method, the fabricated gold nanoparticle conjugates can have surface coverage with functional ligands which can be tuned to be any percent value between 0 and 100%.

Abstract translation: 在本发明中，公开了一种制备稳定的裸胶体金纳米颗粒的方法。 随后可以对纳米颗粒进行部分或全面修饰。 该方法包括使用以大块金为源材料的自顶向下纳米制造方法在液体中制备胶体金纳米颗粒。 这些纳米颗粒的表面改性是通过添加一种或多种类型的配体，每个配体包含对金纳米颗粒表面具有亲和性以产生共轭物的官能团。 由于通过该方法制备的纳米颗粒的高效率和优异的稳定性，所制备的金纳米颗粒共轭物可以具有表面覆盖的功能性配体，其可被调整为0至100％之间的任何百分比值。

公开(公告)号：WO2015183659A1

公开(公告)日：2015-12-03

申请号：PCT/US2015/031731

申请日：2015-05-20

Applicant: IMRA AMERICA, INC.

Inventor： QIAN, Wei ,  LIU, Bing ,  FETTERS, Kori, Michael

IPC: G01N33/58 ,  C12Q1/37

CPC classification number: C12Q1/37 ,  G01N33/587 ,  G01N2333/81 ,  G01N2333/948

Abstract: In the present invention, a method and assay for the detection of proteases and protease inhibitors using colloidal gold nanoparticles and peptide substrates, which are selectively recognized and cleaved by proteases being assayed, is disclosed. In this assay, the mechanism of signal generation relies on peptide sequence induced aggregation of gold nanoparticles, which are used as signal reporters. The peptide sequences that induce aggregation are either the intact peptide substrates or proteolytic fragments of the intact peptide substrate wherein the proteolytic fragments are produced by the protease being assayed. The present invention provides a novel, simple, sensitive, and inexpensive colloidal gold nanoparticle-based colorimetric assay that allows both visual and quantitative detection of proteases and protease inhibitors.

Abstract translation: 在本发明中，公开了使用被测定蛋白酶选择性识别和切割的胶体金纳米颗粒和肽底物检测蛋白酶和蛋白酶抑制剂的方法和测定法。 在该测定中，信号产生的机制依赖于用作信号记录器的金纳米颗粒的肽序列诱导的聚集。 诱导聚集的肽序列是完整肽底物的完整肽底物或蛋白水解片段，其中蛋白水解片段由待测蛋白酶产生。 本发明提供了一种新颖，简单，灵敏和便宜的基于胶体金纳米颗粒的比色测定法，其允许视觉和定量检测蛋白酶和蛋白酶抑制剂。

公开(公告)号：WO2014116767A3

公开(公告)日：2014-07-31

申请号：PCT/US2014/012636

申请日：2014-01-23

Applicant: IMRA AMERICA, INC.

Inventor： ICHIKAWA, Yuki ,  MARCINKEVICUS, Andrius ,  ITO, Masayuki ,  QIAN, Wei

IPC: B01J13/00

Abstract: The present disclosure is directed to methods of preparing stable suspensions of precious metal nanoparticles and methods for attaching bio-molecules to the nanoparticles. The formation of nanoparticles can be accomplished by either chemical synthesis or pulsed laser ablation in a liquid. The present disclosure reveals the importance of controlling the conductivity of the dispersion medium during pulsed laser ablation in a liquid to control the particle size of the nanoparticles. The present disclosure also reveals the importance of adjusting and maintaining the conductivity in a range of 25 μS/cm or less during storage of the nanoparticles and just prior to performing bioconjugation reactions. The control of conductivity is an important process for maintaining the nanoparticles as a stable non-aggregated colloidal suspension in a dispersion medium.

公开(公告)号：WO2012134853A1

公开(公告)日：2012-10-04

申请号：PCT/US2012/029623

申请日：2012-03-19

Applicant: IMRA AMERICA, INC. ,  LIU, Bing ,  QIAN, Wei ,  MURAKAMI, Makoto ,  CHE, Yong

Inventor： LIU, Bing ,  QIAN, Wei ,  MURAKAMI, Makoto ,  CHE, Yong

IPC: G01J3/44

CPC classification number: B05D3/06 ,  B05D7/22 ,  B82Y30/00 ,  B82Y40/00 ,  G01J3/44 ,  G01N21/658 ,  G01N2021/651

Abstract: An apparatus for performing surface-enhanced Raman scattering (SERS) is disclosed wherein an inner surface of a container is coated with SERS active materials such as nanoparticles of noble metals. Such a container can provide a partially enclosed, optical diffuse cavity whose inner surfaces serve for dual purposes of enhancing Raman scattering of the contained analyte and optical integration, therefore improving the efficiency of optical excitation and signal collection. The container may be configured to isolate the SERS active material from the external environment. The container, which may be a cylindrical tube, may be referred to as a SERS tube. Methods of coating the inner wall of a container with pulsed laser ablation and with nanoparticle colloids, respectively, are disclosed.

Abstract translation: 公开了一种用于进行表面增强拉曼散射（SERS）的设备，其中容器的内表面涂覆有SERS活性材料，例如贵金属的纳米颗粒。 这种容器可以提供部分封闭的光学漫射腔，其内表面用于增强所包含的分析物的拉曼散射和光学积分的双重目的，从而提高光学激发和信号采集的效率。 容器可以被配置为将SERS活性材料与外部环境隔离。 可以将圆筒形管的容器称为SERS管。 公开了分别用脉冲激光烧蚀和纳米颗粒胶体涂覆容器内壁的方法。

公开(公告)号：EP3149484A1

公开(公告)日：2017-04-05

申请号：EP15727198.2

申请日：2015-05-20

Applicant: IMRA America, Inc.

Inventor： QIAN, Wei ,  LIU, Bing ,  FETTERS, Kori Michael

IPC: G01N33/58 ,  C12Q1/37

CPC classification number: C12Q1/37 ,  G01N33/587 ,  G01N2333/81 ,  G01N2333/948

Abstract: In the present invention, a method and assay for the detection of proteases and protease inhibitors using colloidal gold nanoparticles and peptide substrates, which are selectively recognized and cleaved by proteases being assayed, is disclosed. In this assay, the mechanism of signal generation relies on peptide sequence induced aggregation of gold nanoparticles, which are used as signal reporters. The peptide sequences that induce aggregation are either the intact peptide substrates or proteolytic fragments of the intact peptide substrate wherein the proteolytic fragments are produced by the protease being assayed. The present invention provides a novel, simple, sensitive, and inexpensive colloidal gold nanoparticle-based colorimetric assay that allows both visual and quantitative detection of proteases and protease inhibitors.

Abstract translation: 在本发明中，公开了使用被测定的蛋白酶选择性识别和切割的胶体金纳米颗粒和肽底物检测蛋白酶和蛋白酶抑制剂的方法和测定法。 在该测定中，信号发生的机制依赖于肽序列诱导的金纳米颗粒的聚集，其被用作信号记录器。 诱导聚集的肽序列是完整肽底物的完整肽底物或蛋白水解片段，其中蛋白水解片段由待测蛋白酶产生。 本发明提供了一种新颖，简单，灵敏和廉价的基于胶体金纳米粒子的比色测定法，其允许视觉和定量检测蛋白酶和蛋白酶抑制剂。