Dr. OligoTM DNA / RNA / OLIGO SYNTHESIZERS

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1 Dr. OligoTM DNA / RNA / OLIGO SYNTHESIZERS High Throughput Oligo Synthesis Synthesize Cleave Deprotect Desalt Elute

2 Dr. Oligo TM The Dr. Oligo TM High Throughput Oligo Synthesizer is available in four versions: Dr. Oligo 96 - One 96 position plate Dr. Oligo Two 96 position plates Dr. Oligo One 384 position plate Dr. Oligo Two 384 position plates Designed and built from the ground up to address the most demanding needs of the end user. The Dr. Oligo boasts a total of 23 amidite delivery systems with up to 19 capable of low volume while remaining easy to operate and maintain. The unique open frame design permits for a wide range of customization options from additional bottles per reagent to double reagent dispensing. All existing and future upgrades can be equipped without having to purchase a brand new instrument and most upgrades can be installed on-site keeping the instrument running with minimum downtime. Featuring a unique parallel dispensing technology, 192 oligos can be synthesized as 20 mers in as low as 2 hours. For any synthesis cycle involving over 192 oligos the overall synthesis time can be further cut by up to 35% when utilizing the double reagent dispensing option. This increases reagent delivery to up to 16 columns simultaneously providing the flexibility to achieve a much higher output in a shorter time frame. Ultra efficient in reagent and gas consumption, the Dr. Oligo keeps operating costs down without sacrificing on the synthesis quality. An additional bottle per reagent can be added to allow one bottle to run completely empty before being changed without having to re-prime the lines. The optional low volume delivery system minimizes waste of expensive amidites by placing the valves and bottles on the nozzle plate thereby reducing the tubing for priming and delivery. HARDWARE OPTIONS & UPGRADES Amidite Dispense Positions The standard instrument comes with 4 standard amidites (ACGT). This option allows you to add additional dispense positions for up to a total of 23 monomer (amidite) positions. Synthesize mixed DNA / RNA and add dyes or other special amidites. Perform synthesis of other small molecules. Add Low Volume Amidite Delivery Systems The standard amidite system volume is 2 ml. The low volume system is 300ul and can allow a reservoir as large as 100 ml Minimize waste of expensive special amidites /dyes. Needs only 300ul to fill the system. Add Dual Volume Amidite Delivery Systems (maximum is 8) The standard amidite system volume is 2 ml. The low volume system is 300ul. The dual volume system has 2 reservoir positions. The lowest volume reservoir can be as large as 100 ml. The 2nd reservoir can be as large as 250 ml. Capable of switching between the low volume and the standard volume reservoirs. Minimize waste of expensive special amidites /dyes. Needs only 300ul to fill the system while still able to use a 2nd reservoir for adding larger quantities of specials if needed.

3 HARDWARE OPTIONS & UPGRADES CONTINUED Add Double Reagent Dispensing System Increase reagent delivery to up to 16 columns at a time. Cut synthesis time by up to 35% providing the flexibility to achive a much higher throughput in a shorter time frame. Oxidizer Dispensing System Add a 2nd Oxidizer delivery system. Perform two different oxidation chemistries in the same synthesis run or in different runs without having to clean the oxidizer system. Wash Bottles The standard instrument has provision for two 4 liter bottles for Wash Reagent. This allows more Wash capacity. Do not have to add Wash Reagent as frequently Deblock Bottles Three Different Gas Inputs The standard instrument has provision for two 4 liter bottle of Deblock Reagent. This allows more Deblock capacity. High quality Argon can be used for the reagent bottles, Nitrogen for purge and drain and dry air for the pneumatics system. Do not have to add Deblock Reagent as frequently. Use less costly Nitrogen for the higher consumed gas for purge & drain and use Argon for the lower consumption function of reagent bottle pressure. Add Larger Capacity Reagent Reservoirs The standard instrument comes with two reservoirs for Activator, Cap-B, Cap-A & Ox. Both are located at the top of the instrument. This option moves the second reservoir (which is the reservoir that would be changed to add more reagent) to a slide out drawer that is located on the cart and changes the bottle cap to fit a larger 4 liter bottle that the reagent would be purchased in. This allows easier access to the reagent bottles for changing them and allows a larger volume bottle on the instrument for less frequent bottle changes. The bottle the reagent is purchased in can be used directly on the instrument. Add Automatic Wash and Purge System The standard Dr. Oligo TM comes with manual valves that must be manually turned to the wash position to wash the nozzles. This option replaces the manual valves with solenoid operated valves so the nozzles can be programmed to automatically wash at the end of a synthesis. The nozzles get washed automatically after a synthesis without user intervention. If nozzles are not washed after synthesis they may eventually get plugged. Add Transfer Bottle Position for the Four Major Amidites The standard instrument has one bottle for the four major amidites (da, DT, dg, dc). This option adds a second bottle cap for each amidite so they can be dissolved in the bottle they were purchased in and then put on the instrument without pouring. The dissolved amidites will automatically transfer to the bottles on the instrument so they can be used. No need to pour amidites into the bottles on the instrument. This will keep the amidites dryer and be more convenient for the operator.

4 HARDWARE OPTIONS & UPGRADES CONTINUED Bottles and Software Configuration to perform Cleavage, Deprotection and Elution There is a chemistry available and documented by Glen Research that enables the process to automate cleaving the oligo from the support, deprotection of the side chains, washing of the oligos to desalt them and elution of the oligos into a plate. This option adds this feature to the Dr. Oligo TM If you have a chemistry that can cleave and deprotect at room temperature and is anhydrous, the Dr. Oligo TM can deliver your oligos cleaved, deprotected and desalted (each in your desired volume of your elution buffer) to you in wells of a 96 well plate. Not available for 384 & 768. Software Features Having experience in oligo synthesis for 30 years and servicing high throughput synthesizers for over 15 years, Biolytic has garnered a high level of understanding regarding the unique challenges that parallel high throughput synthesis presents. The Dr. Oligo TM software utilizes that expertise in delivery systems and oligo synthesis chemistry to optimally manage the hardware for synthesis of short and / or long (150 mers) oligos. The software can automatically adjust reagent deliveries, drain times, reaction times based on the scale of synthesis, the cycle that is being synthesized and the base that is being added. The workflow experience is customizable to the user and the built in protocol editor allows total control over a particular chemistry. Macros can be created for complex procedures or built in macros can be modified to suit your needs. In addition, detailed synthesis information can be quickly viewed from the main screen with the ability to start and stop synthesis at anytime. SOFTWARE FEATURES Feature Description Benefits Map Amidites Map any base code (A,C,G,T) or special to any reservoir Allows the ability to remap the base codes to any specific reservoir without having to edit the sequence in its entirety. Intelligent Auto Reprime of Amidite Nozzles Set a reprime interval and volume. The software will only reprime a nozzle if it has not been used for the number of cycles set as the reprime interval and only if that nozzle is going to be used on the current cycle. Minimizes waste of amidites due to repriming while insuring fresh amidite is always available for use. Separate Auto Reprime Control for Each Special Amidite Set the reprime criteria as described above separately for each special amidite. Minimize waste of special expensive amidites while insuring fresh amidite is used for synthesis.

5 SOFTWARE FEATURES - CONTINUED Variable Amidite Reaction Time Based on the Amidite Used Vary amidite reaction time based on the amidites delivered in each cycle. Reaction times are assigned to each amidite position on the instrument. The longest reaction time is used from all amidites that are delivered in a given cycle. Attach specials amidites at any point in the synthesis automatically and extend the reaction time only for the specials that need it and only for the cycle where the special is attached. Variable Amidite Reaction Time Based on the Cycle Use multipliers to adjust the reaction time of the amidites based on the cycle number. As sequences get longer, more time may be needed for the coupling reaction to complete. This optimizes the cycle time by extending the reaction time only for longer sequences. Fine Tune Reagent Flow Through the Synthesis Media Allows for optimization of chemistry reaction by controlling flow of reagent through synthesis media. Use less reagent resulting in cost savings. Variable Oxidizer Reaction Time based on the Oxidizer Used Vary Oxidizer reaction time based on the Oxidizer delivered in each cycle. Reaction times are assigned to each Oxidizer reagent on the instrument. The longest reaction time is used from the Oxidizers that are delivered in a given cycle. Use a different Oxidation chemistry at any point in the synthesis automatically and extend the reaction time only for the Oxidation chemistries that need it. Variable Oxidizer Reaction Time Based on the Cycle Use multipliers to adjust the reaction time of the Oxidizers based on the cycle number. As sequences get longer, more time may be needed for the Oxidation reaction to complete. This optimizes the cycle time by extending the reaction time only for longer sequences. Variable Hold (Reaction) Time Use multipliers to adjust the reaction time of any reagent based on the cycle number. As sequences get longer, more time may be needed for reactions to complete. This optimizes the cycle time by extending the reaction time only for longer sequences. Variable Drains Based on the % of Finished Oligos Use multipliers to adjust the drain times based on the % of oligos that are finished Use shorter drain times when many oligos are running. As shorter oligos finish, less drain time is needed due to a pressure drop of gas escaping through the finished oligos. Saves time and gas. Vary the Protocol Based on Cycle Run completely different chemistry steps based on the cycle that is running. As oligos get longer, the stoichiometry changes and so does the dynamics of the chemistry. Provides the ability to optimize the chemistry based on the cycle.

6 SOFTWARE FEATURES - CONTINUED View Synthesis Information at Any Time During the Synthesis Show all parameters that were set to perform the current synthesis. Quickly & easily check to verify that all the synthesis parameters are set as intended. Flexible Loading of Oligos onto the Plate(s) Load oligos starting at any location on a plate and from different types of files. Higher degree of flexibility for synthesizing oligos from different orders / customers on the same plate and keep them separate. Manual Mode Auto Clean of Nozzles One button to set an automated manual run to clean all nozzles. Reduces time needed to clean the instrument after synthesis. (Recommended only done if a new synthesis is not going to be started within 6 to 8 hours). Easy Protocol Construction Use macros or subroutines that can be built and called by the main protocol any time. Easier to construct and maintain protocols. Pause Ahead Select a step and cycle to pause after completing. Adds flexibility to deal with the need to pause in the future. Pause to add reagent or to manually prime a special just before it is to be used. This can be set to perform automatically however sometimes users prefer to manually prime if the special is particularly costly. Start Ahead Choose a point to start the synthesis if there is no need to start at the beginning. If a synthesis has to be aborted for some reason you can later continue the synthesis from the point stopped or from any point chosen. Resume an Aborted Synthesis Locate the correct place to resume a synthesis that was aborted. Easily allows information on where to continue an aborted synthesis. Programmed Pause Pre-program pauses in the protocol that will automatically occur during the synthesis. Adds flexibility to allow for pausing the synthesis at a predetermined point to perform a task (refill bottles, remove a special from the instrument etc.). Closed Loop Motion Controller Synthesis will not proceed if the system has not moved to the desired location. The system will pause so the issue can be fixed and then synthesis can resume. Verifies and guarantees delivery of reagents to wells during synthesis

7 SOFTWARE FEATURES - CONTINUED Fail Safe Valve Controller The valves are controlled through intelligent control boards that monitor the electrical condition of the valves, issue errors and pause the synthesis if there is a problem. Keeps the synthesis from proceeding if electrical problems occur with one or more valves. Saves reagents and saves the synthesis. Integrate with LIMS (Lab Management System) A basic implementation is provided to connect with any Lab Management System that can output CSV files or import CSV files. Load all parameters from a single CSV file that is produced by a Lab Management System. Dr. Oligo 384 with Low Volume Amidite Delivery System Dr. Oligo 192 with Standard Amidite Delivery System 250 ml Standard Amidite Bottles Slide Out Cart with Larger Capacity Reagent Reservoirs Please contact our sales representative for purchase advice - sales@biolytic.com Designed and Manufactured in the United States

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