3D-Printed Immunosensor Arrays for Cancer Diagnostics

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.

Biosensors Designed for Clinical Applications

“…Low cost desktop 3D printers (USD 1000-4000) offer revolutionary new options for rapidly designing, optimizing and fabricating high performance-low cost microfluidic array devices [46,47]. 3D printing is an excellent tool for designing and fabricating microfluidic diagnostic devices [48][49][50]. It provides prototypes rapidly and can facilitate design-to-fabrication times of several hours.…”

Printed Electrochemical Biosensors: Opportunities and Metrological Challenges

“…Printed electrochemical biosensors provide novel opportunities for the quantification of proteins, which are peculiar, predictive, diagnostic and prognostic biomarkers of pathophysiological processes [195]. The search for novel protein biomarkers is particularly active for pathologies like cardiovascular disease, cancer or neurodegenerative diseases [196], for which the possibility to rely on novel, low-cost, ultrasensitive, accurate printed biosensors could help to take a step towards early detection, prompting intervention and drug discovery [8,197]. Thus, the early stage protein in particular might be found in blood or in other fluids in concentrations < pg/mL, which are hardly detectable with standard protein analysis [198].…”

Additive Manufacturing as a Means of Gas Sensor Development for Battery Health Monitoring

“…For this purpose, the development of sensor arrays with a wide range of varying materials and performances/possibilities is necessary. Whereas many approaches are based on various synthesis steps, the automatic combination of many complex materials can easily be realized by e.g., additive manufacturing or threedimensional (3D) printing [1]. A large variety of 3D printed sensors have been developed and manufactured recently in the field of biotechnology e.g., for detection of glucose [2], selected medicament [3], trace elements [4], neurotransmitters [5], nucleic acids [6] and/or proteins [7].…”

“…Sharafeldin et al [1] pointed out that 3D printing is very promising even for the detection of cancer and other diseases, because these complex diagnostic devices could be simply connected to portable devices like smartphones with batteries [1]. Also the fabrication of strain sensors by 3D printing has been demonstrated by Liu et al [8] using various printing methods, such as Digital Light Processing (DLP) and Direct Ink Writing (DIW) [8].…”