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(19) United States
(12) Patent Application Publication (io) Pub. No.: US 2005/0106714 Al
Zarur et al. (43) Pub. Date: May 19,2005
Patent Application Publication May 19,2005 Sheet 1 of 2
(54) ROTATABLE REACTOR SYSTEMS AND METHODS
(76) Inventors: Andrey J. Zarur, Winchester, MA
(US); Todd A. Basque, Danvers, MA
(US); Derek T. Stevens, Boston, MA
(US); Nicholas J. Flannery, Brockton,
MA (US); Seth T. Rodgers, Somerville,
MA (US); A. Peter Russo, Woburn,
MA (US); Scott Miller, Somerville,
MA (US); Ian K. MacGregor,
Merrimack, NH (US)
Timothy J. Oyer, Ph.D.
Wolf, Greenfield & Sacks, PC.
600 Atlantic Avenue
Boston, MA 02210-2206 (US)
(21) Appl. No.: 10/927,789
(22) Filed: Aug. 27, 2004
Related U.S. Application Data
(63) Continuation-in-part ol application No. 10/457,015, filed on Jun. 5, 2003.
(60) Provisional application No. 60/498,981, filed on Aug. 29, 2003. Provisional application No. 60/386,322, filed on Jun. 5, 2002.
(51) Int. CI.7 C12M 3/00
(52) U.S. CI 435/288.4; 435/305.3
The present invention generally relates to chips, particularly microfluidic chips, that are rotatable and/or have a generally circular or rotationally symmetric geometry. The chips may be substantially planar in certain instances. In some cases, the chips of the invention can have more than one reaction site, which can, for example, contain cells. The reaction site can be very small, in some cases with a volume of less than about 1 ml. Reactions, transport, and/or other manipulations within the chip can be facilitated by rotating the chip, for example, at tens, hundreds or thousands of revolutions per minute (RPM). In some cases, data may also be written to and/or read from the chip. The chips of the invention can be used, for example, to move fluid from one portion of a chip to another, to concentrate and/or separate a mixture (e.g., a cell suspension), to lyse or fractionate a cell, or the like.
US 2005/0106714 Al
Patent Application Publication May 19,2005 Sheet 2 of 2
ROTATABLE REACTOR SYSTEMS AND
 This application claims the benefit U.S. Provisional Patent Application Ser. No. 60/498,981, filed Aug. 29, 2003, entitled "Rotatable Reactor Systems and Methods" by Zarur, et al.. This application also is a continuation-in-part of co-pending U.S. patent application Ser. No. 10/457,015, filed Jun. 5, 2003, entitled "Reactor Systems Having a Light-Interacting Component," by Scott E. Miller, et al., which claims the benefit of co-pending U.S. Provisional Patent Application Ser. No. 60/386,322, filed Jun. 5, 2002, entitled "Reactor Having Light-Interacting Component," by S. Miller, et al. All of these applications are incorporated herein by reference in their entirety.
FIELD OF THE INVENTION
 This invention generally relates to reactors and reactor systems, and in particular, to reactors and reactor systems that are rotatable and/or have a generally circular geometry.
BACKGROUND OF THE INVENTION
 A wide variety of reaction systems are known for the production of products of chemical and/or biochemical reactions. Chemical plants involving catalysis, biochemical fermenters, pharmaceutical production plants, and a host of other systems are well-known. Biochemical processing may involve the use of a live microorganism (e.g., cells) to produce a substance of interest.
 Cells are cultured for a variety of reasons. Increasingly, cells are cultured for proteins or other valuable materials they produce. Many cells require specific conditions, such as a controlled environment. The presence of nutrients, metabolic gases such as oxygen and/or carbon dioxide, humidity, as well as other factors such as temperature, may affect cell growth. Cells require time to grow, during which favorable conditions must be maintained. In some cases, such as with particular bacterial cells, a successful cell culture may be performed in as little as 24 hours. In other cases, such as with particular mammalian cells, a successful culture may require about 30 days or more.
 Typically, cell cultures are performed in media suitable for cell growth and containing necessary nutrients. The cells are generally cultured in a location, such as an incubator, where the environmental conditions can be controlled. Incubators traditionally range in size from small incubators (e.g., about 1 cubic foot) for a few cultures up to an entire room or rooms where the desired environmental conditions can be carefully maintained.
 Recently, as described in International Patent Application Serial No. PCT/US01/07679, published on Sep. 20, 2001 as WO 01/68257, entitled "Microreactors," incorporated herein by reference, cells have also been cultured on a very small scale (i.e., on the order of a few milliliters or less), so that, among other things, many cultures can be performed in parallel.
SUMMARY OF THE INVENTION
 A variety of reactors and reactor systems that are rotatable and/or have a circular geometry are provided in the
present invention, as well as reactors and reactor systems involving rotatable systems and/or having circular geometry (e.g., around an axis) to perform certain operations of interest. The subject matter of this invention involves, in some cases, interrelated products and/or uses, alternative solutions to a particular problem, and/or a plurality of different uses of a single system or article.
 In one aspect, the invention includes an apparatus. The apparatus, in one set of embodiments, is defined, at least in part, by a substantially planar chip of generally circular shape (i.e., a "disc") having a predetermined reaction site with a volume of less than about 1 ml, where the predetermined reaction site is constructed and arranged to maintain at least one living cell at the site. In another set of embodiments, the apparatus is defined, at least in part, by a disc or other rotatable chip having a predetermined reaction site, where the disc or chip comprises a medium capable of storing information. For example, the disc may have the general dimensions and/or structure of a compact disc (CD) or a digital versatile disc (DVD).
 In another aspect, the invention is a method. In one set of embodiments, the method includes the steps of providing a disc or other rotatable chip comprising a predetermined reaction site having a volume of less than about 1 ml, where the predetermined reaction site is constructed and arranged to maintain at least one living cell at the site; and providing a material in the predetermined reaction site. The method, in another set of embodiments, includes a step of rotating a disc or other rotatable chip around an axis (which may be perpendicular to the plane of the disc or chip in some cases) to allow a material to flow to and/or from the reaction site, i.e., due to the action of centripetal forces acting on the material. The method, in yet another set of embodiments, includes a step of rotating a disc or other rotatable chip around an axis to concentrate a mixture. The method, in yet another set of embodiments, includes a step of rotating a disc or other rotatable chip around an axis to centrifuge cells located in the reaction site. The method, in yet another set of embodiments, includes a step of rotating a disc or other rotatable chip around an axis to break down (lyse) or disrupt the cells located in the reaction site. In some of these cases, the axis may intersect the disc or the chip near the center of the disc or chip, and/or be substantially perpendicular to the disc or chip.
 In another aspect, the invention is directed to a method of making a chip and/or a reactor system, e.g., a rotatable disc or chip as described in any of the embodiments herein. In yet another aspect, the invention is directed to a method of using a chip and/or a reactor system, e.g., a rotatable disc or chip as described in any of the embodiments described herein.
 Other advantages and novel features of the invention will become apparent from the following detailed description of various non-limiting embodiments of the invention when considered in conjunction with the accompanying drawings. In cases where the present specification and a document incorporated by reference include conflicting disclosure, the present specification shall control.
BRIEF DESCRIPTION OF THE DRAWINGS
 Non-limiting embodiments of the present invention will be described by way of example with reference to the