In this paper, a detailed offline multiple fault diagnosis has been presented in conjunction with a detection technique for cross-referencing digital microfluidic biochips. Because of the fundamental mixed expertise, biochips demonstrate distinctive mechanisms of failure and defects. Therefore, for certifying the dependability of a system, both online and offline test procedures are needed. Due to the technological advancements, designs of the DMFBs are getting upgraded day by day. Thus, cross-referencing type of architecture where pin count has been reduced drastically is also receiving attention. Hence, finding multiple faulty electrodes in this type of architecture has become a great challenge. Here, the proposed algorithm can detect multiple faults anywhere within a cross-referencing chip that satisfies the electrode interference challenge as well as dynamic fluidic constraints. The result analysis shows a significant improvement in the fault diagnosis time. © 2021, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.