Single Ended vs. Differential Inputs:

The ADS1x15 breakouts support up to 4 SIngle Ended or 2 Differential inputs.

Single Ended inputs measure the voltage between the analog input channel (A0-A3) and analog ground (GND).

Differential inputs measure the voltage between two analog input channels.  (A0&A1 or A2&A3).

Which should I use?

Single ended inputs give you twice as many inputs. So why would you want to use differential inputs?

Single ended inputs can, by definition, only measure positive voltages. Without the sign bit, you only get an effective 15 bit resolution.

In addition to providing the full 16 bits of resolution and the ability to measure negative voltages, Differential measurements offer more immunity from electromagnetic noise. This is useful when using long signal wires or operating in an electrically noisy environment. This is also desirable when dealing with small signals requiring high gain, since the gain will amplify the noise as well as the signal.

Single Ended Connections:

Connect the signal wire to one of the analog input channels (A0 - A3).  Connect the ground wire to GND.  This diagram shows how to connect an ADXL335 to for measurement of the X, Y and Z axis on analog channels A0, A1 and A2.

Differential Connections:

Differential measurements use a pair of input pins, either A0&A1 or A2&A3.  The following diagram shows connections for differential measurement of the battery voltage on a LiPo charger board.