The human heart beats more than 2.5 billion times in an average lifetime. Now scientists at Vanderbilt University have created a three-dimensional organ-on-a-chip that can mimic the heart’s amazing biomechanical properties.
The I-Wire device consists of a thin thread of human cardiac cells 0.014 inches thick (about the size of 20-pound monofilament fishing line) stretched between two perpendicular wire anchors. The amount of tension on the fiber can be varied by moving the anchors in and out, and the tension is measured with a flexible probe that pushes against the side of the fiber.
The fiber is supported by wires and a frame in an optically clear well that is filled with liquid medium like that which surrounds cardiac cells in the body. The apparatus is mounted on the stage of a powerful optical microscope that records the fiber’s physical changes. The microscope also acts as a spectroscope that can provide information about the chemical changes taking place in the fiber. A floating microelectrode also measures the cells’ electrical activity.
This allows the researchers to reproduce the mechanical conditions of the living heart, which is continually stretching and contracting, in addition to its electrical and biochemical environment.
According to the researchers, the I-Wire system can be used to characterize how cardiac cells respond to electrical stimulation and mechanical loads and can be implemented at low cost, small size and low fluid volumes, which make it suitable for screening drugs and toxins. Because of its potential applications, Vanderbilt University has patented the device.
Unlike other heart-on-a-chip designs, I-Wire allows the researchers to grow cardiac cells under controlled, time-varying tension similar to what they experience in living hearts. As a consequence, the heart cells in the fiber align themselves in alternating dark and light bands, called sarcomeres, which are characteristic of human muscle tissue. The cardiac cells in most other heart-on-a-chip designs do not exhibit this natural organization.
In addition, the researchers have determined that their heart-on-a-chip obeys the Frank-Starling law of the heart. The law, which was discovered by two physiologists in 1918, describes the relationship between the volume of blood filling the heart and the force with which cardiac cells contract. The I-Wire is one of the first heart-on-a-chip devices to do so.