This small, translucent plate is filled with tiny wells – sometimes 60, sometimes 72 – and has been the standard piece of laboratory kit for tissue typing prior to organ transplants since it became the international standard in 1970. It basically looks for tissue compatibility between organ donor and recipient based on the human leucocyte antigen (HLA).
It is named after its American-Japanese inventor, Paul Terasaki, who came up with the idea in 1964, six years before it was adopted as the international standard for what is known as complement dependent cytotoxicity (CDC) cross match. The tray is made of polystyrene and fits easily onto an inverted microscope, with each well holding a maximum volume of 10 micro litres. A truncated cone base in the centre of each well collects cells, allowing the semi-quantitative grading of the immunological reaction between donor lymphocytes and patient’s serum in the crossmatch test. If the recipient has pre-existing antibodies in their serum that can recognise the donor’s cells, and which could potentially cause organ rejection, they will bind to the donor’s cells in the plate and cause cell death (by activating the complement system). Dead cells are easily visualised by addition of a dye. Alternatively, the donor’s HLA type can be determined by screening their cells against a panel of antibodies with known HLA specificity.
The great innovation of the test was that it allowed the handling of small quantities of serum and cells, gaining greater test sensitivity. The micro-cytotoxity test really created the field of histocompatibility as we know it today, allowing the safe transplant of organs and tissues without fear of immediate tissue rejection.
Asked how he came up with the idea in 1964, Terasaki said it emerged out of the necessity of using the smallest amount of serum and cells as possible.
“Necessity is really the mother of invention,” he said in an interview before he died. “Both my technician, John McClelland, and I were unable to venipuncture each other, so we finger poked each other for blood. We had to make enough lymphocytes from capillary tubes of blood for the test.
“Moreover, not being in the blood bank, we had no source of antibodies except left over serum from Rh testing of pregnant women. The microtest permitted 1000 tests to be done with 1 mL of serum. We were able to read 60 tests on one plate within 1 min by attaching buttons on the base of the microscope to an electric typewriter (before the days of computers),” he said.
“Every drop was extremely valuable to us. I can still remember [colleagues] asking why I was so stingy. Four years after its introduction, the microtest was adopted as a standard by the NIH [which is why it is sometimes referred to as the NIH test], and 6 years later at the 1970 Workshop, it was adopted as an international standard.”
The test has been indispensable for determining donor-recipient HLA compatibility, resulting in the near complete prevention of hyperacute and accelerated graft rejection and facilitating safe and effective solid organ transplantation.