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1. 发明授权

US07700363B2 Method for screening crystallization conditions in solution crystal growth 失效
标题翻译：筛选溶液晶体生长中的结晶条件的方法
公开(公告)号：US07700363B2
公开(公告)日：2010-04-20
申请号：US11639211
申请日：2006-12-15
申请人： Lawrence J. DeLucas , Terry L. Bray
发明人： Lawrence J. DeLucas , Terry L. Bray
IPC分类号： G01N33/00
CPC分类号： G01N33/00 , B01J19/0046 , B01J2219/00313 , B01J2219/00317 , B01J2219/00369 , B01J2219/00479 , B01J2219/00495 , B01J2219/00585 , B01J2219/00599 , B01J2219/00693 , B01J2219/00707 , B01J2219/00725 , B01J2219/00756 , B01L3/06 , B01L3/5085 , B01L2300/041 , B01L2300/0819 , C30B7/00 , C30B29/58 , C30B35/00 , C40B40/10 , C40B50/08 , C40B60/14 , G01N25/14 , Y10T436/25
摘要： A method of screening protein crystal growth conditions with picogram to microgram amounts of protein in picoliter or nanoliter volumes is provided. A preferred method comprises a microarray with a plurality of microchambers in the microarray. A protein solution is placed into the micro-chambers by an automated dispensing mechanism. The protein crystal growth conditions of each of the micro-chambers is adjusted so that the protein crystal growth conditions in at least two of the micro-chambers differs. Crystallization of the protein solution in the micro-chambers is effected. For example, crystallization can be effected by a precipitate solution and/or placing an oil barrier over the protein solution. Protein crystal growth in the micro-chambers is then observed.
摘要翻译：提供了以皮克到微克量的蛋白质以皮升或纳升体积筛选蛋白质晶体生长条件的方法。优选的方法包括在微阵列中具有多个微室的微阵列。通过自动分配机构将蛋白质溶液置于微室中。调整每个微室的蛋白质晶体生长条件，使得至少两个微室中的蛋白质晶体生长条件不同。实现微室中的蛋白质溶液的结晶。例如，可以通过沉淀溶液和/或在蛋白质溶液上放置油屏障来实现结晶。然后观察微室中的蛋白质晶体生长。

2. 发明授权

US07214540B2 Method for screening crystallization conditions in solution crystal growth 有权
标题翻译：筛选溶液晶体生长中的结晶条件的方法
公开(公告)号：US07214540B2
公开(公告)日：2007-05-08
申请号：US09947665
申请日：2001-09-06
申请人： Lawrence J. DeLucas , Terry L. Bray
发明人： Lawrence J. DeLucas , Terry L. Bray
IPC分类号： G01N33/00
CPC分类号： G01N33/00 , B01J19/0046 , B01J2219/00313 , B01J2219/00317 , B01J2219/00369 , B01J2219/00479 , B01J2219/00495 , B01J2219/00585 , B01J2219/00599 , B01J2219/00693 , B01J2219/00707 , B01J2219/00725 , B01J2219/00756 , B01L3/06 , B01L3/5085 , B01L2300/041 , B01L2300/0819 , C30B7/00 , C30B29/58 , C30B35/00 , C40B40/10 , C40B50/08 , C40B60/14 , G01N25/14 , Y10T436/25
摘要： A method of screening protein crystal growth conditions on a nano or meso scale comprises providing a micro-electromechanical chip with a plurality of micro-chambers in the micro-electromechanical chip. A protein solution is placed into the micro-chambers by an automated jet type dispensing means with nano or meso scale precision. The protein crystal growth conditions of each of the micro-chambers is adjusted so that the protein crystal growth conditions of each of the micro-chambers differs. Crystallization of the protein solution in the micro-chambers is effected. Protein crystal growth in the micro-chambers is then observed.
摘要翻译：在纳米或中尺度上筛选蛋白质晶体生长条件的方法包括在微机电芯片中提供具有多个微室的微机电芯片。蛋白质溶液通过具有纳米或中尺度精度的自动喷射型分配装置放入微室中。调整每个微室的蛋白质晶体生长条件，使得每个微室的蛋白质晶体生长条件不同。实现微室中的蛋白质溶液的结晶。然后观察微室中的蛋白质晶体生长。

3. 发明授权

US06406903B2 Dynamically controlled crystal growth system 失效
标题翻译：动态控制晶体生长系统
公开(公告)号：US06406903B2
公开(公告)日：2002-06-18
申请号：US09131729
申请日：1998-08-10
申请人： Terry L. Bray , Larry J. Kim , Michael Harrington , Lawrence J. DeLucas
发明人： Terry L. Bray , Larry J. Kim , Michael Harrington , Lawrence J. DeLucas
IPC分类号： C12N700
CPC分类号： C12N9/2462 , C07K2299/00 , C30B7/00 , C30B29/58 , Y10S117/901 , Y10T117/1008
摘要： Crystal growth can be initiated and controlled by dynamically controlled vapor diffusion or temperature change. In one aspect, the present invention uses a precisely controlled vapor diffusion approach to monitor and control protein crystal growth. The system utilizes a humidity sensor and various interfaces under computer control to effect virtually any evaporation rate from a number of different growth solutions simultaneously by means of an evaporative gas flow. A static laser light scattering sensor can be used to detect aggregation events and trigger a change in the evaporation rate for a growth solution. A control/follower configuration can be used to actively monitor one chamber and accurately control replicate chambers relative to the control chamber. In a second aspect, the invention exploits the varying solubility of proteins versus temperature to control the growth of protein crystals. This system contains miniature thermoelectric devices under microcomputer control that change temperature as needed to grow crystals of a given protein. Complex temperature ramps are possible using this approach. A static laser light scattering probe also can be used in this system as a non-invasive probe for detection of aggregation events. The automated dynamic control system provides systematic and predictable responses with regard to crystal size. These systems can be used for microgravity crystallization projects, for example in a space shuttle, and for crystallization work under terrestial conditions. The present invention is particularly useful for macromolecular crystallization, e.g. for proteins, polypeptides, nucleic acids, viruses and virus particles.
摘要翻译：可以通过动态控制的蒸气扩散或温度变化来启动和控制晶体生长。一方面，本发明使用精确控制的蒸气扩散方法来监测和控制蛋白质晶体生长。该系统利用湿度传感器和计算机控制下的各种界面，通过蒸发气体流同时实现多种不同生长方案的任何蒸发速率。可以使用静态激光散射传感器来检测聚集事件并触发生长溶液的蒸发速率的变化。可以使用控制/跟随器配置来主动地监视一个室并且相对于控制室精确地控制重复的腔室。在第二方面，本发明利用蛋白质相对于温度的不同溶解度来控制蛋白质晶体的生长。该系统包含微电脑控制下的微型热电装置，根据需要改变温度以生长给定蛋白质的晶体。使用这种方法可以实现复杂的温度斜坡。静态激光散射探头也可用于该系统中作为检测聚集事件的非侵入式探头。自动化动态控制系统提供关于晶体尺寸的系统和可预测的响应。这些系统可用于微重力结晶项目，例如在航天飞机中，以及在地下条件下的结晶作业。本发明特别适用于大分子结晶，例如，用于蛋白质，多肽，核酸，病毒和病毒颗粒。

4. 发明授权

US07250305B2 Use of dye to distinguish salt and protein crystals under microcrystallization conditions 有权
标题翻译：在微结晶条件下使用染料来区分盐和蛋白质晶体
公开(公告)号：US07250305B2
公开(公告)日：2007-07-31
申请号：US10208576
申请日：2002-07-30
申请人： Larry Cosenza , Terry L. Bray , Lawrence J. DeLucas , Thomas E. Gester , David T. Hamrick
发明人： Larry Cosenza , Terry L. Bray , Lawrence J. DeLucas , Thomas E. Gester , David T. Hamrick
IPC分类号： G01N33/00
CPC分类号： G01N33/00 , C07K1/306 , C30B7/00 , C30B29/58 , G01N25/147 , G01N33/6839
摘要： An improved method of screening crystal growth conditions is provided wherein molecules are crystallized from solutions containing dyes. These dyes are selectively incorporated or associated with crystals of particular character thereby rendering crystals of particular character colored and improving detection of the dyed crystals. A preferred method involves use of dyes in protein solutions overlayed by oil. Use of oil allows the use of small volumes of solution and facilitates the screening of large numbers of crystallization conditions in arrays using automated devices that dispense appropriate solutions to generate crystallization trials, overlay crystallization trials with an oil, provide appropriate conditions conducive to crystallization and enhance detection of dyed (colored) or undyed (uncolored) crystals that result.
摘要翻译：提供了一种筛选晶体生长条件的改进方法，其中分子从含有染料的溶液中结晶。这些染料被选择性地掺入或与具有特定特征的晶体结合，从而使具有特定特征的晶体着色并改善了染色晶体的检测。优选的方法包括在由油覆盖的蛋白质溶液中使用染料。油的使用允许使用小体积的溶液，并且有助于使用自动化装置筛选大量结晶条件，分配合适的溶液以产生结晶试验，用油覆盖结晶试验，提供有利于结晶和增强的适当条件检测染色（有色）或未染色（未着色）晶体。

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