sensors Review 3D-Printed Immunosensor Arrays for Cancer Diagnostics Mohamed Sharafeldin 1 , Karteek Kadimisetty 2 , Ketki S. Bhalerao 1 , Tianqi Chen 1 and James F. Rusling 1,3,4, * 1 Department of Chemistry, University of Connecticut, Storrs, CT 06269, USA; mohamed.sharafeldin@uconn.edu (M.S.); ketki.bhalerao@uconn.edu (K.S.B.); tianqi.chen@uconn.edu (T.C.) 2 LifeSensors Inc., 271 Great Valley Parkway, Suite 100, Malvern, PA 19355, USA; karteek.kadimisetty@gmail.com 3 Department of Surgery and Neag Cancer Center, UConn Health, Farmington, CT 06032, USA 4 School of Chemistry, National University of Ireland at Galway, Galway H91 TK33, Ireland * Correspondence: james.rusling@uconn.edu Received: 20 July 2020; Accepted: 6 August 2020; Published: 12 August 2020   Abstract: Detecting cancer at an early stage of disease progression promises better treatment outcomes and longer lifespans for cancer survivors. Research has been directed towards the development of accessible and highly sensitive cancer diagnostic tools, many of which rely on protein biomarkers and biomarker panels which are overexpressed in body fluids and associated with different types of cancer. Protein biomarker detection for point-of-care (POC) use requires the development of sensitive, noninvasive liquid biopsy cancer diagnostics that overcome the limitations and low sensitivities associated with current dependence upon imaging and invasive biopsies. Among many endeavors to produce user-friendly, semi-automated, and sensitive protein biomarker sensors, 3D printing is rapidly becoming an important contemporary tool for achieving these goals. Supported by the widely available selection of affordable desktop 3D printers and diverse printing options, 3D printing is becoming a standard tool for developing low-cost immunosensors that can also be used to make final commercial products. In the last few years, 3D printing platforms have been used to produce complex sensor devices with high resolution, tailored towards researchers’ and clinicians’ needs and limited only by their imagination. Unlike traditional subtractive manufacturing, 3D printing, also known as additive manufacturing, has drastically reduced the time of sensor and sensor array development while offering excellent sensitivity at a fraction of the cost of conventional technologies such as photolithography. In this review, we offer a comprehensive description of 3D printing techniques commonly used to develop immunosensors, arrays, and microfluidic arrays. In addition, recent applications utilizing 3D printing in immunosensors integrated with different signal transduction strategies are described. These applications include electrochemical, chemiluminescent (CL), and electrochemiluminescent (ECL) 3D-printed immunosensors. Finally, we discuss current challenges and limitations associated with available 3D printing technology and future directions of this field. Keywords: 3D printing; POC; microfluidics; immunosensor; cancer; biomarkers 1. Introduction Cancer is one of the leading causes of death worldwide. Globally, it was responsible for approximately 9.6 million deaths in 2018 [1]. A major contributing factor to the high mortality is late diagnosis due to the unavailability of modern diagnostic tools in low income countries and their limited accessibility or application in developed countries. Currently, cancer diagnosis rely on techniques such as magnetic resonance imaging (MRI), computed tomography (CT), endoscopy, mammography Sensors 2020, 20, 4514; doi:10.3390/s20164514 www.mdpi.com/journal/sensors