Methods and devices are provided for determining the presence and/or
concentration of at least one analyte in a sample of low transmissivity.
In the subject methods, a forward beam and a backward beam are produced
by or introduced into an interferometer from at least one infrared
radiation source. The forward beam is passed into the sample and then
collected to produce a sample beam while the backward beam is passed into
a reference and then collected to provide a reference beam. The sample
and reference beams are recombined either optically into a null beam
which is detected at a single detector or electronically nulled after
detection on two separate detectors. The presence, and often amount, of
at least one analyte in the sample is then derived from the detected null
beam. Also provided are devices for practicing the above methods. The
subject methods and devices are suitable for use in a variety of
different applications, including the detection of the presence, and
amount, of one or more blood analytes in a physiological sample, such as
blood, tissue or derivatives thereof.