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Formulator User Manual

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1. 2 1 Inputs The Inputs panel lists information about the ingredients used in the dispense The column corresponds to the input positions on the top of the Formulator with 0 indicating the input water line Click on the header to sort the ingredient input cells in ascending or descending order The Status of an ingredient can be Empty No ingredient at that location Unprimed An ingredient has been identified but is not ready to dispense Primed An ingredient is ready to dispense and should not be removed from the system Washing The ingredient is being washed and should not be removed Washed The ingredient has been washed and can be safely removed The Stock Name shows the ingredient s name The Liquid Class for an ingredient can be Normal Medium High or Very High This is set automatically in Rock Maker or manually in the Dispense List panel H Staus Stock Name A 0 Unpimed 100 00 3 Water Al FPimed Yellow AZ Unpimed Blue Fig 4 Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 2 1 Dispense List 5 Dispense List 22500 m Lipid Reqd Mn Bize 6530 OO000000000_ E alow Normal 6 940 0 0050 100 150 2 E 100 00 amp water Monal 15 780 10 100 0 35 0 90 0 85 Fig 5 Fie blue pellows dl ba Plate Type Greiner Rectangle Well Volume
2. and which nozzles will be used and where they are used for a specific microplate type Rows PlateLength 128 Columns qe Vector Wash For more information on how to modify a microplate definition See section 4 3 Plate Definitions Origin X 32 96 Y 18 02 750 00 M indicates a move command VS indicates a valve state The Delay shows the time in milliseconds up to 9999 spent in each valve state Move commands are executed at a constant speed and do not use delays The Data for a move command are the Cartesian coordinates for a valve state they are three binary vectors which give the state of all valves in the system the first vector represents the internal system valves the second represents the 96 dispense valves and the third represents the ingredient valves The box at the lower right corner shows the total time in minutes for the dispense Well Shape Circle Well Width 7 RowOngin 12 RowPitch 9 Column Origin 8 Column Pitch 9 Map aimon Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 2 5 File Menu 8 File gt Open gt Dispense List Loads a dispense list to the Formulator software Note Files must be in dispense list format dl txt Keyboard shortcut CTRL O File gt Open gt Sequence Fi
3. F2 J Device gt Load Plate Fig 13 Prepares the plate stage to be loaded with a microplate alow fast y Device gt Home Stages Resets the position of the plate stage to 0 0 0 on XYZ Can be used to find plate position if position is lost Device gt Handscan Allows the user to manually enter a barcode for a dispense list or an ingredient if printed labels are unavailable Keyboard shortcut CRTL H Device gt Internal Wash Flushes the system and microfluidic chip with water Keyboard shortcut CTRL I Device gt External Wash Flushes water out of the microfluidic chip nozzles to remove any excess ingredients Keyboard shortcut CTRL E Device gt Wash All Inputs Washes the septa cap inputs The system will only wash inputs that are actually attached Keyboard shortcut CTRL Shift W Device gt Prepare for Shutdown Purges the system of liquid so that it can be shut down safely Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 3 Using the Formulator 9 3 1 Starting Up Turn on the power switch on the back panel Wait until the computer has recognized and connected to the Formulator Start the Formulator software Make sure the three indicators in the bottom left panel of the software screen are green If not see Maintenance amp Troubleshooting See Fig 14 System will automatic
4. The Valves panel provides visual representations of the microfluidic chip an individual instance of a microfluidic valve cluster and the various air fluid valves internal to the system Microfluidic Chip ott ttt tt een eee pt ttt tt tl ott Tt tt tt ae ERE HE Ean EEE SEE _ i t E tT TT tT The microfluidic chip has 96 outputs in a 12 x 8 grid representing a 96 well plate Green indicates that a valve is open red indicates that a valve is shut This graphic provides a real time visualization of a dispense as each valve opens and shuts A particular valve can be manually opened and shut by clicking on the representative box this is an advanced operation Internal Fluid Air Valves These valves are internal to the system and should only be manipulated by Formulatrix support personnel Mouse over an icon to see the name of the corresponding valve Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 2 3 Valves Continued Each of the 96 outputs has its own microfluidic valve cluster Each valve cluster has two diaphragms 200nL and 2 5uL and three valves to control the flow of liquid These elements on the microfluidic valve cluster can be either green open or red shut Clicking on an element toggles its state across all 96 outputs this is an advanced operation The valve cluster graphic provides a visualization
5. of the stages of a dispense pulling liquid through the input valve into one of the diaphragms and expelling liquid through either the output valve which leads to the plate or the purge valve which leads to the waste line 2 4 Sequence Input Valve 200nL Diaphragm 2 5uL Diaphragm Purge Valve Output Valve Fig 10 The Sequence panel shows the stage movements and valve states which make up a particular dispense Any change in the dispense list parameters causes the software to generate a fresh sequence for the updated dispense n Sequence Delay M35 92675 Y 1 318 Z 55 0645 1110001000 CODD O0D0000000000000 00000 1100001000 0000 0DDDODO00000iiiid oggi OOOTOO TOON OOOO pp00000000000000000 OOOOOOT000 DOOD 0DDDD OOOO OOOKK ee i 1110001000 C000 OD000000 OCMC eile KK DOOD DODO OO0OO 1100001000 0000 000000000000iCtiiie EEN i OOO1IOO1000 00ootto000d00000000t0 0000001000 0000TONI0000000000 1110001000 00000000 OCs 1100001000 OODDODDD00O0000000O le 0001001000 CD00 RDDDOIO eee 0000001000 douat OOOO 1110001000 C000 00000000000000ciie 2 eS ee eee ee 08 35 62 A OO A Ea DEE E eB Perret Fig 11 Microplate Layout 2 5 File Menu File Note File gt New gt Microplate Definition Mimer SES Adapted The Microplate Layout window allows a user to adjust the proper microplate layout for the Formulator and choose the orientation of the chip offsets
6. on the floor near the Formulator 8 Plug the Pressure and Vacuum lines into the appropriate ports on the back of the Formulator Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 2 Control Software 4 Formulator fel oloooooo nooo 0 005 0 10 0 15 0 2 10 100 0 35 0 30 0 85 Jnpimed 100 00 4 Water Primed Yelow Inpimed Bhe Ernply E mpiy E mipiy Empty Plate Type Greines Rectangle p w Well Volume Sequence _Deloy _ ES Data Input O stabe Priming 111000100000 DODNIO0O OIRO 110000100000 00000000 00ta a o B ooo1o01o000N d N00 CO COONooONNOSONNOeNNNOANOORANOOCANNACONONoONAANOAAAeOANONONN DO00001 gogoo goggogoggggiggggogng OOOO 111000100000 OOD0D0000000000000000000000000 Ono I 110000100000 DODD 0000 00000000000000000000000000000000000000000000000000000000 DODIDO1O0000 D00000 0T Md CO00001 00000 DODO 000 O00nRIIIooOooOOOoOOOooD 111000100000 00000000 igiggi OOOO 110000100000 OOD0D0D000000000000000000000000 i i i 0 00010000000 OOOO O00 OOOO 0 o000001 00000 QOBTOO0OQ000000000000000 it 0 111000100000 ODDO 00 DO NDOSONDOS0 00000000000 0000000000 0000000000000000000000000 i a7 ge Dispense sequence for pense kat Blue yelow diw EER 001815 001815 25 00 5000 20000 Primed input Al stock fellow bquid class Homma volume 1800 8 crclels
7. 100 00 The Dispense List panel shows how each ingredient will be dispensed into the plate The box to the left of the Stock Name shows whether the ingredient is primed or unprimed we A green box with a check mark means an ingredient is primed E An empty green box means an ingredient is unprimed ie A red box means that the ingredient has not been identified Stock Name shows the ingredient s name as defined in the dispense list file Barcode displays an ingredient s barcode number if any Liquid Class classifies an ingredient s viscosity as Normal Medium High or Very High Click on a Liquid Class cell to reveal a drop down menu where the user can manually set the liquid class for each ingredient Required Vol pL shows the total volume in microliters of each ingredient that will be dispensed over the entire plate Note This number does not include dead volume The dead volume is approximately 12mL per ingredient per dispense Min Vol uL shows the smallest volume that will be dispensed into any one well Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 2 2 Dispense List Continued Dispense Volumes shows the individual well 10 0 0 ee volumes for each ingredient in sequential order aso from A1 to H12 Mouse over the cell to reveal a i graphic of the entire plate 10 0 1 A Green to Beige Gradient repres
8. Documentation version 1 0 last updated 11 12 2009 FORMULATRIX Formulator User Manual Table of Contents 1 General Information 2 Iss Se EXONS ES e a aa 2 1 2 Requirements tor Operation 2 DE eting Wee Orn ete e ee 3 2 CONTO SIENTE a eee 4 A ANOS ae ae 4 22 Dispenselit lt ey pee cee 4 Rao VOOS m 5 2A e UEN E ee 7 2 5 File Menu a a 7 20 Device MENU E 8 53 USINE Wn POM le O meea 9 3 la el GING UPD e er e 9 a2 MOWING WINS SACA m 9 D reting DIS pense LSS e e e 9 II UNM All ate DISPENSE E e ae 10 3 SNIENE DOWN 11 4 Maintenance amp Troubleshooting 11 4 1 Formulatrix Support information 11 4 2 Coverage Information 11 4 3 Proper usage and maintenance I2 4 4 Plate Definitions 12 AN IS Wasmin SK Outs C8 OS mee 13 Formulator 16 Formulator 34 This is a living document Please check http www formulatrix com documentation formdoc pdf for version updates Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 1 General Information 1 1 Components 1 2 1 2 Ingredient Inputs Inputs for Nalgene bottles and Falcon tubes Microfluidic chip Has 96 outputs with two metering chambers each Diaphragms are 200n
9. L and 2 5uL and can fill and dispense as fast as three times per second 3 Plate holder Compatible with all 96 192 and 384 well plates Compatible with some 24 and 48 well plates with optional adapter 4 oS O Barcode scanner Scans identification labels on ingredients or plates Ventilation fan Removes excess heat from unit USB port Outlet for USB connection Power switch Turns the Formulator on and off Air liquid lines Inputs for pressure vacuum water and optional secondary wash line Output for waste Requirements for Operation The Formulator requires the following peripheral elements in order to run 1 2 Electrical connection 110 240V 50 60Hz 130W typical 200W max Standard or European outlet A supply of pressure and vacuum that meets the following specifications Formulatrix can supply a pump box that meets these specifications or a connection to lab air vacuum can be established upon request Note Lab air vacuum connectors must be of a standard type Pressure 30 psi 0 15 cfm 2 0 bar 4 3 Ipm Vacuum 22 inHg 0 2 cfm 750 mbar 5 7 Ipm A computer that meets the following specifications Windows XP or Vista Minimum of 256MB RAM Minimum 100MB free HD space Minimum 1 open USB Port Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 1 2 Requirements for Operation Continu
10. all run an internal wash Repeat until no bubbles are visible in the tubes leading up to the microfluidic chip Note Make sure to check that there is enough water in the water bottle and the waste bottle isn t full The instrument is now ready for use Fig 14 3 2 Moving the Stage The hand can be moved manually with the Motion Control Pad see Fig 13 in previous section The left and right arrows on the Control Pad move the stage on the X Axis The up and down arrows located around the C button with the left right arrows moves the stage on the Y Axis The right hand up and down arrows move the stage on the Z Axis The slider on the bottom sets the movement speed from slow to fast Note Care should be taken when manually driving the stage not to impact the chip 3 3 Creating Dispense Lists The user can create a dispense list using one of the following methods Rock Maker integration Formulatrix s Rock Maker software provides a platform to easily create dispense lists It can generate barcodes for printed labels to automatically retrieve both dispense lists and ingredient names Manually If Rock Maker is not available the user can employ a spreadsheet program or any text editor to create a dispense list J beH eral Molen Foe Ot Poet View Help SBS pi fat Blue Redi 160 00 5 water Before creating a dispense list manually please note the following Any forgotten or misplace
11. cale the dispense volume by typing in a new number here The Dispense Volumes of each ingredient will automatically scale to the new volume once the focus moves out of this field After the dispense is finished the Formulator can automatically wash out the chip nozzles and or ingredient bottles depending on the configuration settings Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 3 5 Shutting Down 11 Most of these operations will be automatically performed by the software if properly configured Wash all ingredient bottles Right click on an ingredient name in the Ingredients panel gt Wash all Run the shutdown sequence Device gt Prepare for Shutdown Close the software Turn off the power switch on the back panel 4 Maintenance amp Troubleshooting 4 1 Formulatrix Support Information Formulatrix does not recommend opening your Formulator for on site maintenance For any issues in the running of your Formulator please contact the Formulatrix Support team via email support formulatrix com Note This email address is monitored 24 7 and will be responded to as soon as a support team member is available to do so 4 2 Coverage Information What is software maintenance Software maintenance includes all product upgrades excluding installation on site support to fix problems as necessary phone support and remote suppor
12. d characters will cause an error when the file is opened in the Formulator software Enter data carefully Formulator control software is case and character sensitive Enter stock names barcodes and liquid classes carefully using the appropriate capital letters and spacing All fields are tab delimited To create a dispense list do the following On the first line enter the name of the plate definition file for the plate being used in the dispense This file should be located in the DataFiles folder under the main program folder See 2 5 Microplate Definitions for instructions on creating new plate definition files Press Enter to end the line Create a new line for each ingredient in the dispense Enter the Stock Name Press Tab Choose from one of these two barcode options If label printing equipment is available Leave this space blank as the Formulator will automatically record the barcode when the user scans the ingredient Press Tab If label printing equipment is not available Type in the barcode being careful to preserve all capital letters and spacing Press Tab Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 10 Choose from one of these two liquid class options Type in Normal Medium High or Very High being careful to preserve all capital letters and spacing Press Tab Leave this space bla
13. ed 4 A supply of distilled or filtered water for washing the system and filling out dispenses e Formulatrix can supply a source container with appropriate fittings upon request 5 Areceptacle for collecting waste fluid e Formulatrix can supply a receptacle with appropriate fittings upon request 1 3 Setting Up the Formulator 1 Download and install the latest software and any needed drivers As of Release 10 Beta 7 installation of drivers and backup of previous software are automatic Contact support formulatrix com for the most recent software 2 Take the Formulator out of the box and set on a sturdy lab table 3 Tip Formulator backwards to unscrew shipping bolt in the center of the unit s base shown below 4 Plug the power cable and USB cable into the back of the Formulator Plug the other end of the power cable into a wall socket Plug the USB cable into any USB port on a computer 5 Connect a 1 4 OD tube from the water source container to the Water port on the back of the Formulator Push firmly until the tube is secure within the fittings To remove the tube push down on the port ring while pulling back on the tube Repeat for the Waste line Note Do not position liquid containers so that the liquid level can rise above the height of the microfluidic chip 6 Connect the Formulator to a supply of air and vacuum using 5 32 OD tubing IF USING A FORMULATRIX PUMP BOX AND CABLE 7 Set the pump box
14. entify all the ingredients using one of the following methods Scan the barcode of the ingredient and place it on any of the input locations within 10 seconds of scanning The software will automatically identify it Place the ingredient on any of the input locations and the drag and drop the name of the ingredient from the Dispense panel onto the appropriate location on the Inputs panel Note The ingredient slots closest to the front left corner of the unit provide lower dead volume and more efficient flow for viscous liquids If an ingredient has not been associated with a liquid class it will have a yellow question mark icon next to it Select a liquid class from the drop down list in the Dispense panel This selection will be automatically stored along with the ingredient s name Once all parameters are properly set the Sequence panel will be populated with the dispense commands and the time to dispense will be displayed in the lower right corner At this point the dispense cab be run Device gt Run or F5 or certain parameters can be edited on the fly Plate type The user can select an alternate plate type from the drop down list Only plate types with the appropriate number of wells will be displayed The software does not know how much volume the plates can hold It is the user s responsibility to ensure that the selected plate can contain the entire volume dispensed Well volume The user can manually s
15. ents ano een the amount to be dispensed in each i i well Pure beige means nothing will a00 laso be dispensed 2 The darkest green is the highest oa s0 fioa fiso a amount of liquid to be dispensed File displays the dispense list s file name Plate Type lists the plate definition file for the dispense The user can manually select an alternate plate definition from the drop down menu o_o i K 7 a N Well Volume indicates the total volume of all ingredients to be dispensed into each well The user can manually scale the dispense volume by typing in a new number here The Dispense Volumes of each ingredient will automatically scale to accommodate the new volume once the focus moves out of this field Modifying the Dispense Order Dispense List The ingredients will dispense in the order that they are listed from top to bottom Right click on an ingredient name to reveal a menu to change the order of ingredients to be dispensed Stock Mame Barcode 3 Move Up Ctrl U Select Move Up Ctrl U to move an ingredient up in the dispense Move Down Ctrl D Select Move Down Ctrl D to move an ingredient down in the dispense Split Ctri T Select Split Ctrl T brings up another dialog to split the ingredient into AED StL one of a particular volume and the rest in the other tulle a Then move each instance of the ingredient to the desired place in the list Fig 7 2 3 Valves
16. le Loads a sequence file to the Formulator software Note Files must be in sequence list format seq txt Keyboard shortcut CTRL Shift O File gt Open gt Microplate Definition Loads a microplate definition and brings up the microplate layout window see Fig File gt Save Sequence CTRL S and File gt Clear Sequence A sequence can be edited in the Formulator software and saved for reuse or cleared as necessary File gt Advanced View Toggles on off Advanced mode Advanced mode displays the Valves and Sequence sections of the software as seen in Fig File gt Options Brings up the Options window The options window is tabbed and allows for 3 user customizations 1 Timeout Values Sets how often the Formulator will wash inputs automatically Never default Immediately After Run and Custom allows you to set a custom increment of time 2 Dispense List Two options for sorting of dispense list items Enable auto sorting and set Liquid Class over stock for priority in sorting 3 User Interface Toggles on Advanced Mode for startup 2 6 Device Menu Motion Control Pad Device gt Run Starts a dispense or sequence Keyboard shortcut F5 Device gt Stop Gc Stops a dispense or sequence Keyboard shortcut Shift F5 Device gt Toggle Motion Pad Opens the motion control pad to allow the user to move the plate arm on the X Y and Z stages see figure 13 Keyboard shortcut
17. nk and press Tab The user will have the opportunity to select the Liquid Class in the Formulator software after the dispense list is loaded Enter the volume of ingredient in microliters to be dispensed into each well of the plate separated by a tab The order of wells is A1 A12 B1 B12 etc Make sure to enter precisely the same number of volumes as there are wells in the plate definition file Repeat the previous step for each ingredient in the dispense Make sure that water is the last ingredient to be dispensed This ensures that very small volumes of the other ingredients will be dispensed properly Add an empty line after the final ingredient Save the file to the DispenseLists folder under the main program folder Tst file andi with ot Sets hard return below thela ingrediant F unt Bes Motepad a Pike Dee Poort Yas Piip SES pd tmi fi bus a m j Red ui 4 10 13 PI 7h Mi 1 di a5 i Ti i 1 F T gl a Th ri 5 ce 4 ro at 3 4 Running a Dispense Note This section assumes that a dispense list and plate definitions have been created as described above Open the dispense list file using one of the following methods Scan the barcode that corresponds to the dispense list Go to File gt Open Dispense List or CTRL O and select the dispense list file If any ingredients are not present and or identified they will show up in red Place and id
18. t via remote connectivity tools like VPN access WebEx GoTOMyPC com etc What is hardware maintenance Hardware maintenance includes all parts labor on site support phone support and remote support via remote connectivity tools like VPN access WebEx GoToMyPC com etc required to keep the hardware operational It also includes monitoring nightly diagnostics and responding to it What is not covered under software and hardware maintenance Hardware maintenance does not include damage done to the system due to abuse of the system customer modifications of the system or misuse of the system Travel and shipping expenses including shipping of defective parts during the maintenance warranty period will be billed separately at actual cost A fixed cost option can be provided for this if desired Software and hardware maintenance do not include extended user training This is included as part of the hardware installation Are computers covered under maintenance Computers supplied by Formulatrix are not covered under maintenance We purchase a minimum 2 year on site service plan from the computer manufacturer and transfer this warranty to the customer Formulatrix will assist with diagnosing computer errors and re installing software but the customer must work with the computer manufacturer directly resolve hardware issues What is priority shipping and travel You can choose to pay for travel and priority shipping in ad
19. ter is automatically placed last in the dispense order but if you move it make sure that there is at least 10ul of a non viscous reagent after the last viscous one If your Formulator does not have a wash station remember to do an external wash with a deep well in the hand after each plate to prevent reagents from drying up in the nozzle Don t hesitate to email or call Formulatrix with any questions We are happy to help 4 4 Plate Definitions The plate should be dispensed 1 2mm below the chip For small diameter wells the nozzles should be centered over the well For wide wells like the Deep Well wells and 96 hanging drop plates the nozzle should be about 2mm from the edge of the well to reduce splashing See figure 17 Fig 17 Plate Tuning Instructions First remove any plate from the hand If you leave a plate on the hand it could run into the chip when you first check the position Open the microplate definition of the plate you want to edit If you are creating a new one open Deep Well pd txt and Save As something else To check the current dispensing position right click on the first item in the vector box and choose Move To Position Then put the plate in the hand to see if it is right If you want to change the position make sure the plate is not in the hand and right click the item in the vector box and choose Modify Position and the numbers should turn red Put the plate in the hand and
20. use the number pad to position the wells under the nozzles 9 and 3 are up and down 8 and 2 are in and out 4 and 6 are left and right Alternatively you can open the motion pad via Device gt Toggle Motion Pad to control the plate When the plate is in the proper position right click the vector item and choose End Position Modification Save the position by choosing File gt Save You may need to reload the current dispense list if there is already one loaded before the position change takes effect Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 4 5 Washing Septa Caps 13 septa Cap Washing Things you will need the cap a syringe water How to 1 Fill the syringe with water 2 Place syringe tip in the center hole on the inside of the cap And then squirt water through the cap You should see water squirting out the other side Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228
21. vance for up to one year Please ask your sales or support person for a quotation What happens if am out of maintenance and I have a problem If you are out of maintenance then you can choose to purchase support time at an hourly rate and pay for time and materials for hardware related issues separately What happens if am out of maintenance and decide want to get back on maintenance If you want to get back on maintenance then you will have to back pay maintenance For example if your maintenance expired in June 07 and you decided to renew maintenance in December 07 then you would have to back pay maintenance to cover the time period between June and December In this scenario purchasing 1 year of maintenance would cover you from June 07 to June 08 Any support calls purchased during a back payment period will be credited towards future maintenance payments Copyright 2009 Formulatrix All Rights Reserved Formulator is a trademark owned by Formulatrix www formulatrix com 1 7817880228 4 3 Proper Usage amp Maintenance 12 We recommend putting paraffin over the caps if you are going to store ingredients in the bottles for more than a week Remember to screw the caps tightly so they don t leak when turned upside down Some computers take longer than others to connect to the Formulator so you might need to wait for up to 10 seconds after turning on the Formulator to start the software Wa

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