The Tropospheric Water and Cloud ICE (TWICE) instrument has been developed to provide global observations of upper tropospheric water vapor and ice particle sizes in clouds and their variation with season and climate environment. TWICE is a wide-band millimeter- and sub-millimeter wave radiometer measuring at 16 frequencies in 7 frequency bands from 118 GHz to 850 GHz. The TWICE instrument development was led by Colorado State University (CSU) in partnership with the NASA/Caltech Jet Propulsion Laboratory (JPL) and Northrop Grumman Corporation (NGC). TWICE uses 25-nm InP High Electron Mobility Transistor (HEMT) low-noise amplifier-based (LNA) front-ends operating from 230 to 880 GHz and integrated into single-module receivers from input feed horn to output post-detection voltage. The amplifier front-end and direct-detection architecture provides low noise operation at these sub-millimeter wave frequencies, as well as dramatically reducing the power required, as compared to traditional mixer-based heterodyne architectures. The TWICE radiometers perform end-to-end calibration once each scan by viewing both cold space (2.7 K) reflector and an ambient calibration target at a precisely known thermodynamic temperature. TWICE is capable of operating in a 6U CubeSat, with dimensions of up to 34 cm x 20 cm x 10 cm and mass of up to 12 kg. TWICE can easily be adapted for high-altitude aircraft operation to raise the instrument to TRL 6 and to provide observations for model validation. Finally, the TWICE instrument is adaptable for other small satellite form factors in combination with complementary instruments, including millimeter-wave radar for clouds and precipitation, to enhance its capability to perform measurements for climate prediction and weather forecasting.