BioDot’s core competency in quantitative, small drop, non-contact dispensing is supported by a number of patents:

US 5738728 | Precision Metered Aerosol Dispensing Apparatus

A reagent dispensing valve particularly adapted for dispensing precise microfluidic quantities of fluids. The valve includes a valve portion and a solenoid actuator that are in fluid isolation from one another. The valve portion includes a plunger and seat combination and the actuator is substantially decoupled from the fluid path through the valve.

The fluid path through the valve is substantially non-tortuous, thereby minimizing localized fluid pressure drops, and hence undesirable gaseous bubble precipitation within the fluid. The valve is also configured to substantially prevent bubble accumulation. The valve can further include a bubble trap for trapping and removing bubbles.

US 5738728

US 5743960 | Precision Metered Solenoid Valve Dispenser

A reagent dispensing apparatus is provided including a positive displacement syringe pump in series with a solenoid valve dispenser. The pump is controlled by a stepper motor or the like to provide an incremental quantity or continuous flow of reagent to the solenoid valve dispenser.

The solenoid valve is opened and closed in a predetermined frequency and duty cycle to dispense droplets of reagent onto a target substrate at the metered flow rate.

US 5743960

US 5741554 | Method of Dispensing a Liquid Reagent

A method for dispensing precise quantities of reagents is disclosed including the steps of providing positive displacement syringe pump in series with a dispenser, such as a solenoid valve dispenser.

The pump is controlled by a stepper motor or the like to provide an incremental quantity or continuous flow of reagent to the dispenser. The dispenser is operated in accordance with predetermined parameters to dispense droplets of reagent onto a target substrate at the metered flow rate.

US 5741554

US 5916524 | Dispensing Apparatus Having Improved Dynamic Range

A method and apparatus for dispensing precise quantities of reagents is disclosed including a positive displacement syringe pump in series with a dispenser, such as an aerosol dispenser or solenoid valve dispenser.

The pump is controlled by a stepper motor or the like to provide an incremental quantity or continuous flow of reagent to the dispenser. The pump and dispenser are operated in cooperation with one another such that the quantity and/or flow rate of liquid dispensed by the dispenser can be precisely metered substantially independently of the particular operating parameters of said dispenser to attain a desired flow rate, droplet size or mist quality, droplet frequency and/or droplet velocity.

US 5916524

US 6576295 B2 | Method for Dispensing Reagent onto Substrate

A method and apparatus for dispensing precise quantities of reagents is disclosed including a positive displacement syringe pump in series with a dispenser, such as an aerosol dispenser or solenoid valve dispenser.

The pump is controlled by a stepper motor or the like to provide an incremental quantity or continuous flow of reagent to the dispenser.

The pump and dispenser are operated in cooperation with one another such that the quantity and/or flow rate of liquid dispensed by the dispenser can be precisely metered substantially independently of the particular operating parameters of said dispenser to attain a desired flow rate, droplet size or mist quality, droplet frequency and/or droplet velocity.

US 6576295 B2

US 7541068 B2 | Method For Dispensing Reagent onto a Substrate

A method and apparatus for dispensing precise quantities of reagents is disclosed including a positive displacement syringe pump in series with a dispenser, such as an aerosol dispenser or solenoid valve dispenser.

The pump is controlled by a stepper motor or the like to provide an incremental quantity or continuous flow of reagent to the dispenser.

The pump and dispenser are operated in cooperation with one another such that the quantity and/or flow rate of liquid dispensed by the dispenser can be precisely metered substantially independently of the particular operating parameters of said dispenser to attain a desired flow rate, droplet size or mist quality, droplet frequency and/or droplet velocity.

US 7541068 B2

US RE38281 E1, China 97198220.1, Germany 912253, UK 912253 | Dispensing Apparatus Having Improved Dynamic Range

A method and apparatus for dispensing precise quantities of reagents is disclosed including a positive displacement syringe pump in series with a dispenser, such as an aerosol dispenser or solenoid valve dispenser.

The pump is controlled by a stepper motor or the like to provide an incremental quantity or continuous flow of reagent to the dispenser.

The pump and dispenser are operated in cooperation with one another such that the quantity and/or flow rate of liquid dispensed by the dispenser can be precisely metered substantially independently of the particular operating parameters of said dispenser to attain a desired flow rate, droplet size or mist quality, droplet frequency and/or droplet velocity.

US RE38281 E1
China 97198220.1

US 6537505 B1 | Reagent Dispensing Valve

A reagent dispensing apparatus is provided including a positive displacement syringe pump in series with an air brush dispenser.

The pump is controlled by a stepper motor or the like to provide incremental or continuous flow of reagent to the air brush dispenser. The air brush dispenser mixes the predetermined incremental quantity or continuous flow of reagent with pressurized air to atomize the reagent and produce an aerosol spray pattern which coats the substrate.

US 6537505 B1

Germany 1485204, EPC 1485204, UK 1485204 | Method and Apparatus For Dispersing Reagent Droplets Below a Fluid Surface Using Non-Contact Dispensing

The invention relates generally to dispensing of fluid droplets and in particular to methods and systems of dispersing, suspending or arranging microfluidic or sub-microfluidic volumes of droplets of chemical, biological or other reagents or liquids below the surface of a cover or host fluid using non-contact dispensing for creating an assay or reaction that produces a detectable signal or a by-product such as a harvestable protein crystal.

Advantageously, the preferred embodiments substantially prevent evaporation of valuable reagents. Another advantage, in the case of miscible reagents, is that the drop velocities provide good mixing. Yet another advantage is that, in the non-contact approach, the dispensing nozzle or tip is not immersed into the host fluid, thereby facilitating cleaning.

Germany 1485204
EPC 1485204
UK 1485204

Germany 1324829, EPC 1324829, UK 1324829 | Method For High-Speed Microfluidic Dispensing Using Text File Control

The invention relates to methods and systems for high-speed precision dispensing and/or aspirating of microfluidic quantities of reagents and other liquids. The operation of the systems is controlled by data accessed from a customized user-defined text file.

Advantageously, the use of such text file control allows high-speed precision dispensing of one or more reagents with a wide dynamic range of dispense volumes in complex combinatorial patterns, ratios and arrays onto or into multiple predetermined locations of a desired target or substrate.

This is particularly advantageous when a large number of permutations of different reagents and permutations of reagent volume ratios are involved. The systems may be operated in a high frequency modulated mode to further improve accuracy and reliability.

Germany 1324829
EPC 1324829
UK 1324829

US 6551557 B1 | Tip Design and Random Access Array for Microfluidic Transfer

The present invention relates to a ceramic tip and a random access print head for the transfer of microfluidic quantities of fluid. The print head can randomly collect and deposit fluid samples to transfer the samples from a source plate to a target.

The print head can also be programmed to create a direct map of the fluid samples from the source plate on the target or to create any desired pattern or print on the target. The tip and print head can be used for a wide variety of applications such as DNA microarraying and compound reformatting. In one preferred embodiment, the tip is used as a capillary or “gravity” pin to draw or collect source fluid and “spot” or deposit the fluid onto the target via physical contact (touch-off).

In another preferred embodiment, the tip is used in conjunction with an aspirate-dispense system to actively aspirate source fluid and deposit the fluid via a contact or non-contact approach. The tip provides improved, accurate, and repeatable microfluidic transfer.

US 6551557 B1

US 7736591 B2 | Method and Apparatus for Liquid Dispensing (“Ceramic Tip”)

The present invention relates to a ceramic tip and a random access print head for the transfer of microfluidic quantities of fluid. The print head can randomly collect and deposit fluid samples to transfer the samples from a source plate to a target.

The print head can also be programmed to create a direct map of the fluid samples from the source plate on the target or to create any desired pattern or print on the target. The tip and print head can be used for a wide variety of applications such as DNA microarraying and compound reformatting.

In one preferred embodiment, the tip is used as a capillary or “gravity” pin to draw or collect source fluid and “spot” or deposit the fluid onto the target via physical contact (touch-off). In another preferred embodiment, the tip is used in conjunction with an aspirate-dispense system to actively aspirate source fluid and deposit the fluid via a contact or non-contact approach. The tip provides improved, accurate, and repeatable microfluidic transfer.

US 7736591 B2

US 7470547 B2 | Methods and Systems For Dispensing Sub-Microfluidic Drops (“Electric Field”)

The invention relates generally to dispensing of fluids and, in particular, to methods and systems for dispensing microfluidic or sub-microfluidic volumes of droplets of chemical, biological or other reagents or liquids. Embodiments of the invention have particular efficacy in accurately dispensing small drops having volumes from about 100 nL down into the picoliter range.

US 7470547 B2

US 6063339 | Method and Apparatus For High-Speed Dot Array Dispensing

A dispensing apparatus and method is provided for accurately and precisely dispensing various desired patterns of reagent onto a substrate or other receptive surface or receptacle.

The invention provides high-speed on-the-fly dispensing of various desired reagent patterns as provided by the operator in the form of a graphic bit map file.

In one embodiment the dispensing apparatus comprises a dispensing head having an inlet end and an outlet end. The dispensing head is responsive to a first signal to dispense droplets of liquid reagent onto a substrate. The substrate or dispensing head are secured in association with a table or carriage. The table is responsive to a second signal for providing for relative X, X-Y or X-Y-Z motion between the substrate and the dispensing head.

A controller is adapted to receive data representative of a desired reagent pattern and to output and coordinate the first and second signals so as to cause relative motion between the substrate and the dispensing head and, simultaneously, to cause the dispensing head to dispense droplets of liquid reagent at one or more desired locations on the substrate to form the desired reagent pattern.

The controller adjusts the phase lag or lead between the first and second signals to compensate for the magnitude of relative motion between the substrate and the dispensing head given the probable trajectory of each droplet of liquid reagent.

Optionally, a direct current fluid source, such as a positive displacement pump, may be provided in series with the dispensing head for precisely regulating the quantity or flow rate of liquid reagent provided to the dispensing head.

US 6063339

US 7754439 B2 | Method and System for the Analysis of High Density Cells Samples

Methods for forming cell arrays of multiple cell samples arranged substantially in a monolayer on a single substrate particularly suited for diagnostic analysis are disclosed.

The cell arrays are formed with a high-speed dispensing apparatus capable of dispensing small volumes in precise, complex patterns.

Also disclosed are substrates upon which cell arrays may be formed, and methods for conducting diagnostic analyses on the formed cell arrays.

US 7754439 B2

US 8323882 B2 | Method and System for the Analysis of High Density Cells Samples

Methods for forming cell arrays of multiple cell samples arranged substantially in a monolayer on a single substrate particularly suited for diagnostic analysis are disclosed.

The cell arrays are formed with a high-speed dispensing apparatus capable of dispensing small volumes in precise, complex patterns. Also disclosed are substrates upon which cell arrays may be formed, and methods for conducting diagnostic analyses on the formed cell arrays.

US 8323882 B2