Systems and methods for determining cell contractility

A method of determining the contractile function of one or more contracting cells or a contracting microtissue using ultrasound, the method comprising:

• emitting, using a transducer, ultrasound energy to the one or more contracting cells or the contracting microtissue at a frequency of between about 20 MHz and about 500 MHz;
• detecting, through the transducer, ultrasound waves reflected from the one or more contracting cells or the contracting microtissue;
• sampling, by the transducer, said detected waves to produce ultrasound signals comprising:
• a first signal amplitude representing an upper surface of the one or more contracting cells or of the contracting microtissue when the one or more contracting cells or the contracting microtissue is in a rest state;
• a second signal amplitude representing a lower surface of the one or more contracting cells or of the contracting microtissue when the one or more contracting cells or the contracting microtissue is in the rest state;
• a third signal amplitude representing the upper surface of the one or more contracting cells or of the contracting microtissue when the one or more contracting cells or the contracting microtissue is in a contraction state;
• and a fourth signal amplitude representing the lower surface of the one or more contracting cells or of the contracting microtissue when the one or more contracting cells or the contracting microtissue is in the contraction state;
• receiving the signals from the transducer at an ultrasound controller;
• computing with a processor one or more relationships between the signals wherein the one or more relationships comprise at least one of:
• acquired signal amplitude;
• acquired signal phase;
• propagation delay;
• and, time of flight;
• analyzing, by the processor, the one or more computed relationships to determine the contractile function of the one or more contracting cells or the contracting microtissue;
• determining a rest height by determining a difference between the first signal amplitude and the second signal amplitude;
• determining a contraction height by determining a difference between the third signal amplitude and the fourth signal amplitude;
• and
• determining a contraction distance by determining a difference between the rest height and the contraction height.

A method of measuring the effect an agent has on the contractile function of one or more contracting cells or a contracting microtissue using ultrasound, the method comprising:

• emitting, using a transducer, ultrasound energy to the one or more contracting cells or the contracting microtissue at a frequency of between about 20 MHz and about 500 MHz;
• detecting, through the transducer, ultrasound waves reflected from the one or more contracting cells or the contracting microtissue contacted with an agent;
• sampling, by the transducer, said detected waves to produce ultrasound signals comprising:
• a first signal amplitude representing an upper surface of the one or more contracting cells or of the contracting microtissue in the absence of contact with the agent when the one or more contracting cells or the contracting microtissue is in a rest state;
• a second signal amplitude representing a lower surface of the one or more contracting cells or of the contracting microtissue in the absence of contact with the agent when the one or more contracting cells or the contracting microtissue is in the rest state;
• a third signal amplitude representing the upper surface of the one or more contracting cells or of the contracting microtissue in the absence of contact with the agent when the one or more contracting cells or the contracting microtissue is in a contraction state;
• a fourth signal amplitude representing the lower surface of the one or more contracting cells or of the contracting microtissue in the absence of contact with the agent when the one or more contracting cells or the contracting microtissue is in the contraction state;
• a fifth signal amplitude representing the upper surface of the one or more contracting cells or of the contracting microtissue contacted with the agent when the one or more contracting cells or the contracting microtissue is in the rest state;
• a sixth signal amplitude representing the lower surface of the one or more contracting cells or of the contracting microtissue contacted with the agent when the one or more contracting cells or the contracting microtissue is in the rest state;
• a seventh signal amplitude representing the upper surface of the one or more contracting cells or of the contracting microtissue contacted with the agent when the one or more contracting cells or the contracting microtissue is in the contraction state;
• and an eighth signal amplitude representing the lower surface of the one or more contracting cells or of the contracting microtissue contacted with the agent when the one or more contracting cells or the contracting microtissue is in the contraction state;
• receiving the signals from the transducer at an ultrasound controller;
• computing with a processor one or more relationships between the signals wherein the one or more relationships comprise at least one of:
• acquired signal amplitude;
• acquired signal phase;
• propagation delay;
• and, time of flight;
• analyzing, by the processor, the one or more computed relationship to determine the contractile function of the one or more contracting cells or the contracting microtissue contacted with the agent;
• comparing the contractile function of the one or more contracting cells or the contracting microtissue with the contractile function of the one or more contracting cells or the contracting microtissue in the absence of contact with the agent;
• determining an absence rest height by determining a difference between the first signal amplitude and the second signal amplitude;
• determining an absence contraction height by determining a difference between the third signal amplitude and the fourth signal amplitude;
• determining an absence contraction distance by determining a difference between the absence rest height and the absence contraction height;
• determining a contact rest height by determining a difference between the fifth signal amplitude and the sixth signal amplitude;
• determining a contact contraction height by determining a difference between the seventh signal amplitude and the eighth signal amplitude;
• determining a contact contraction distance by determining a difference between the contact rest height and the contact contraction height;
• and
• comparing the absence contraction distance with the contact contraction distance.