Apparatus for microscopic worm observation

Apparatus according to any preceding claim wherein the movable table is coupled to an oscillating mechanism configured to oscillate the reservoir support platform (7) in a horizontal plane by an amplitude less than a diameter (D) of the nutrient reservoir (5).

Apparatus according to any preceding claim wherein the movable table is coupled to a height actuator mechanism (14) to actuate a vertical movement of the reservoirs support platform with the height actuator mechanism.

Apparatus according to any preceding claim wherein there are a plurality of said chip holders arranged substantially in parallel on the support structure.

Apparatus according to any preceding claim in conjunction with said microfluidic chips (2) wherein each microfluidic chip comprises a plurality of parallel microfluidic channels (54), each microfluidic channel passing fluidically through a plurality of successive culture chambers (52).

Apparatus according to the preceding claim wherein each microfluidic channel (54) comprises a pump side coupling orifice (54a) and a reservoir side coupling orifice (54b), the orifices configured for insertably receiving in a sealing manner ends of hollow tubes.

Apparatus according to any preceding claim wherein the microfluidic chips are fluidically coupled to corresponding fluidic tubes connectors (4) pluggably coupled to the chip holder (3) and sealingly lodging ends of fluidic tubes (36) that extends to the pump and/or valve system.

Apparatus according to any preceding claim further comprising a tube tip sealing plate (9) comprising a support frame (11) and an elastomer pad (13) movable under the tips (26b) of the hollow tubes and configured for sealingly pressing said elastomer pads (13) against said tips during a corresponding operation step of the apparatus.

Apparatus according to the preceding claim wherein said corresponding operation step comprises a debubbling operation of the fluidic channels within the microfluidic chip.

Apparatus according to any preceding claim wherein reservoir side coupling orifices (54b) of the microfluidic chip and corresponding hollow tubes (26) are arranged in a spaced out manner in both X and Y orthogonal directions of a horizontal plane, such that the hollow tubes are spaced out according to a two-dimensional grid, the hollow tubes being arranged at intersections of a substantially square or rectangular grid.

Apparatus according to any preceding claim wherein the pump side fluidic coupling (24) comprises a plurality of hollow tubes coupled to the chip holder (3) and inserted into corresponding pump side coupling orifices (54a) of the microfluidic chip (2).

Apparatus according to any preceding claim wherein the chip holder comprises a base (18) and a cover (20) pivotally coupled to the base, movable from an open position in which the microfluidic chip (2) may be lodged on the base (18), and movable to a closed position held by a closing mechanism (22) clamping the microfluidic chip within the chip holder.

Apparatus according to any preceding claim wherein the chip holder comprises a viewing window (21) in both a base (18) and cover (20) to allow light to shine through from a bottom of the microfluidic chip to a top side viewable by a microscope (44).

Apparatus according to any preceding claim wherein an imaging system (42, 44) comprising a microscope (44), a lighting system (38), and a computing system (46) connected to the valve system (V) and pump (P), actuation mechanism (14, 16), lighting system (38) and imaging system (42, 44), is configured for automatic operation of microscopic worms in the culture chambers (52) of the microfluidic chip (2) and imaging the microscopic worms in said culture chambers over a period of time ranging between a few days to a few weeks.

Method of operating a microscopic worm culture and observation apparatus (1) according to any of the preceding claims comprising a worm feeding operation including operating the pump (P) in a feeding direction to draw liquid from the nutrient reservoirs (5) into the culture chambers (52) of the microfluidic chips, and stirring the liquid in the nutrient reservoirs (5) by actuation of the oscillating movement and the height adjustment movement of the reservoirs support platform (7), either simultaneously during the operation of the pump or immediately prior to operation of the pump.

Method according to the preceding claim wherein operation of the apparatus comprises a chip priming step after loading of a new microfluidic chip in the apparatus, the chip priming step comprising operating the pump in a direction of fluid flow exiting the hollow tubes (a priming direction) to pump a priming liquid through the microfluidic channels (54) and culture chambers (52) of the microfluidic chips until said priming liquid exits tips (26b) of the hollow tubes (26).

Method according to any preceding claim wherein operation of the apparatus includes a chip debubbling operation, said debubbling operation including pumping a liquid in a priming direction while pressing an elastomer pad (13) against said tips to sealingly close them and generate an overpressure within the microfluidic channels.

Method according to any preceding claim in which operation of the apparatus comprises a worm loading on chip operation including positioning nutrient reservoirs containing microscopic worms to be injected in culture chambers (52) of the microfluidic chips (2) in nutrient reservoirs (5), placing the nutrient reservoirs under the tips of the hollow tubes and inserting the tips into the liquid, operating the pump with pulses to inject microscopic worms into the culture chambers (52).

Method according to any preceding claim in which operation of the apparatus includes a reservoir exchange step including removing the tips of the hollow tubes out of a first set of reservoirs, operating the pump in a priming direction to create droplets at the tips, and subsequently moving the reservoir support platform (7) to insert the tips of the hollow tubes into a new set of nutrient reservoirs (5).