# US 9,752,175 B2 · Systems and methods to detect biofilm streamer growth and their uses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,752,175 B2 - Document ID: US9752175B2 - Status: Granted - Kind: B2 - Application number: 14/589,845 - Filed: 2015-01-05 - Published: 2015-07-09 - Granted: 2017-09-05 - Earliest claimed: 2014-01-06 - Assignees: The Trustees of Princeton University - Applicants: The Trustees of Princeton University - Inventors: Bonnie L. Bassler; Howard A. Stone; Knut Drescher; Yi Shen - Web page: https://patentgrep.com/patent/US9752175B2 ## CPC - C12Q 1/18: Testing for antimicrobial activity of a material - C12M 41/36: {of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404)} - C12Q 1/02: involving viable microorganisms - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} ## Abstract Methods and systems of measuring biofilms and/or biofilm streamers are presented. The system has at least one channel, a biofilm streamer promotion element, a fluid capable of moving along the channel, wherein the fluid has a flow driven by a controlled pressure; and a measuring element capable of measuring a flow rate of the fluid through the channel. Additionally, methods of screening for compound(s) that promote and/or inhibit biofilm and/or biofilm streamers using this system are also presented. Uses of the system, methods and identified compounds are presented for medical and/or industrial environments. ## Claims ### Claim 1 A system for measuring biofilm streamers comprising: a. at least one channel, wherein the channel comprises an inlet, an outlet, a lumen, and at least one biofilm streamer promotion element, wherein a fluid moves through the lumen in a flow driven by a controlled pressure; b measuring element capable of measuring a flow rate of the fluid through the channel, wherein the measuring element: (i) receives the fluid in an effluent collecting element after the fluid moves through the lumen; (ii) measures the weight of the received fluid as a function of time using an analytical balance; and (iii) communicates the measured weight to a computer, wherein the computer determines the change in weight of the received fluid as a function of time. ### Claim 2 (depends on 1) The system of claim 1, wherein the controlled pressure is provided by a pumping element or gravity. ### Claim 3 (depends on 2) The system of claim 2, wherein the pumping element is a syringe, a weight, or a pump. ### Claim 4 (depends on 1) The system of claim 1, wherein the biofilm streamer comprises bacterium capable of producing a biofilm streamer. ### Claim 5 (depends on 1) The system of claim 1, wherein the effluent collecting element is a dish. ### Claim 6 (depends on 2) The system of claim 2, wherein the pumping element is a reservoir suspended above the height of the effluent collecting element, wherein a height differential between the reservoir and the effluent collecting element determines the controlled pressure applied to the fluid. ### Claim 7 (depends on 1) The system of claim 1 further comprising a substrate. ### Claim 8 (depends on 7) The system of claim 7, wherein the substrate is a glass coverslip. ### Claim 9 (depends on 1) The system of claim 1, further comprising a microscope capable of imaging the channel. ### Claim 10 (depends on 9) The system of claim 9, wherein the microscope is capable of imaging biofilm streamer growth. ### Claim 11 (depends on 9) The system of claim 9, wherein the microscope is capable of imaging biofilm streamer morphology. ### Claim 12 (depends on 9) The system of claim 9, wherein the microscope is a confocal laser scanning microscope or an epifluorescence microscope. ### Claim 13 (depends on 1) The system of claim 1, wherein the biofilm streamer promotion element is selected from: a curved channel, a channel with at least one turn, a channel with at least one corner, an edge projecting into the lumen of the channel, a mound projecting into the lumen of the channel, a channel with roughened surfaces, and one or more objects placed within the channel lumen. ### Claim 14 (depends on 1) The system of claim 1, wherein the channel has at least 2, 3, 4, 5, 6, 7, 8, 9, 10 or 36 corners. ### Claim 15 (depends on 1) The system of claim 1, wherein the channel has 1 turn about every 400 um. ### Claim 16 (depends on 1) The system of claim 1, wherein the flow of the fluid is laminar flow. ### Claim 17 (depends on 1) The system of claim 1, wherein the flow of the fluid is turbulent flow. ### Claim 18 (depends on 1) The system of claim 1, wherein the flow is characterized by a Reynolds number of less than 2000. ### Claim 19 (depends on 1) The system of claim 1, wherein the flow is characterized by a Reynolds number of greater than 2000. ### Claim 20 (depends on 1) The system of claim 1, wherein the flow rate comprises a shear stress of between 0.01 and 100 Pa. ### Claim 21 (depends on 1) The system of claim 1, wherein the biofilm streamer promotion element is amorphous particles of fluoropolymer placed within the channel lumen. ### Claim 22 (depends on 1) The system of claim 1, wherein the biofilm streamer promotion element is a channel comprising welded polypropylene feed spacer mesh. ### Claim 23 (depends on 1) The system of claim 1, wherein the channel is circular. ### Claim 24 (depends on 1) The system of claim 1, wherein the system further comprises a three-inlet port capable of being opened and closed. ### Claim 25 (depends on 24) The system of claim 24, wherein the three-inlet port further comprises multilayer microfluidic gates. ### Claim 26 (depends on 1) The system of claim 1, wherein the channel is selected from: a stent, a pipe, or a cooling tower. ### Claim 27 (depends on 1) The system of claim 1, wherein the computer continually samples the weight of the received fluid in the effluent collecting element as a function of time and converts the weight of the received fluid to a flow rate. ### Claim 28 (depends on 1) The system of claim 1, wherein the computer periodically samples the weight of the received fluid in the effluent collecting element as a function of time and converts the weight of the received fluid to a flow rate. ### Claim 29 (depends on 1) The system of claim 1, wherein the flow rate comprises a shear stress of between 0.01 and 10 Pa. ### Claim 30 (depends on 1) A method of measuring a biofilm streamer comprising: a. passing a fluid through the system of claim 1; b. monitoring the flow rate over time; and c. determining either the time until clogging (T) or the duration of the clogging transition (τ). ### Claim 31 (depends on 30) The method of claim 30, wherein the method further comprises imaging the growth of the biofilm streamer over time. ### Claim 32 (depends on 30) The method of claim 30, wherein the method further comprises imaging the morphology of the biofilm streamer over time. ### Claim 33 (depends on 30) The method of claim 30, wherein the method further comprises: a. adding a test compound to the fluid; and b. comparing the time until clogging (T) or the duration of the clogging transition (τ) in the presence and in the absence of said test compound. ### Claim 34 (depends on 30) The method of claim 30, wherein the method further comprises: a. adding a test compound to the fluid; and b. comparing the growth or morphology of the biofilm streamer in the presence and in the absence of said test compound.