Innovations and Versatility in Modern Microarray Technology

Microarrays have been critical components of biomedical and clinical research strategies since their first mention in a 1995 study. Initially designed to measure gene expression, or transcription, this technique has since been expanded and improved upon to analyze many other biochemical sample types such as proteins or small molecules.

New and innovative advancements in microarray technology mean that modern microarrays remain a fast and reliable solution for a variety of high-throughput needs, supporting fields such as biomarker and drug discovery.

To find out more about the opportunities provided by modern microarray techniques, Technology Networks spoke with Dr. Iain McWilliam, CEO of Arrayjet. McWilliam also discusses contactless microarray printing technologies and the advantages that these tools can deliver for high-throughput screening.

Sarah Whelan (SW): Can you briefly explain what microarrays are and what they are used for?

Iain McWilliam (IM): A microarray is normally a glass slide spotted with many thousands of biological or chemical probes immobilized in a miniature 2D grid. A sample of interest is then incubated on the microarray and specific interactions are detected with fluorescent markers. Most commonly, microarrays are used for high-throughput screening, hit detection in drug discovery and multiplex diagnostics. They are often referred to as microchips for laboratory tests.

SW: Early microarrays were focused on DNA analysis, what else can you print and analyze with this technique?

IM: Modern microarrays can be printed with proteins, antibodies, antigens, glycans, cell lysates and small molecules. This makes them useful for a wide range of applications – including proteomics, antibody characterization, biomarker discovery, point-of-care diagnostics, target identification and drug discovery – in addition to their “original” purpose of analyzing gene expression.

SW: What are the key features of inkjet microarray printers, and how do they work?

IM: Microarrays require tiny volumes of thousands of samples to be dispensed precisely and consistently. Arrayjet’s microarrayers use an industrial-grade inkjet printhead, designed for high-quality graphics, that has been adapted with patented engineering to print biochemical samples.

Samples are loaded into the base of the printhead with a specialized aspirator. The aspirator detaches and the printhead glides across the surface, depositing samples in a user-defined pattern without stopping or making contact. The whole print-space is contained within a HEPA-filtered environment with tightly controlled humidity and temperature. High-speed cameras mounted by the printhead follow the printing and feed images to our AI-driven software, guaranteeing print quality in real time.

Altogether, this means inkjet microarrayers print with the highest accuracy, reliability and speed.

SW: What advantages does this type of contactless array printing technology have over other printing technologies?

IM: When first invented, microarrays were printed by using pins to spot samples directly onto a surface. More recently, contactless microarray options are favored as they are faster and more reliable, with reduced cross-contamination and better spot morphology.

Many contactless dispensing instruments use glass tips, akin to a drawn-glass pipette, but these are difficult to calibrate, can limit layout options, break easily and cost thousands of dollars to replace. In contrast, an inkjet printhead is robust and can switch microarray layouts at the push of a button.

For screening operations, throughput is essential, and the overwhelming advantage of inkjet microarrays is speed. They also have high reproducibility, great flexibility and accommodate simple walk-away operation. The newer, faster inkjet approach means microarrays are a cost-effective option for screening applications where they may not have been considered before.

SW: Can you tell us more about your ArrayPlex spot-on-spot microarray platform? What are the applications of this technique, and what additional benefits does it provide?

IM: ArrayPlex™ is our patented, array-based technique for rapid combinatorial library screening. It involves printing and immobilizing a set of capture samples onto a set of slides, then printing a second test library on top. The throughput is phenomenal – over two million unique interactions can be generated in a weekly experimental cycle. We most commonly use this for immunotherapeutic antibody hit detection by screening human tissue samples against hybridoma antibody libraries, but the technology is compatible with other proteins, nucleic acids and small molecules.

SW: Can you give us some examples of recent successes using inkjet microarray technologies?

IM: A particularly exciting area right now is drug screening for small molecules and biologics. Drug hunters searching for new platforms have turned to microarrays as an alternative to traditional high-throughput screening methods and mass spectrometry approaches.

For small molecules, Arrayjet took processes pioneered by groups at Massachusetts Institute of Technology, the National Cancer Institute and Scripps, and made them accessible with simplified immobilization and detection protocols, in the first commercial platform for small molecule microarrays. Tens of thousands of small molecule drug-like compounds can be printed on a slide and incubated with RNA or proteins of interest to look for novel ligand–target hits.

Elsewhere, for biomarker discovery, we recently published an application note to support the transfer of a reverse-phase protein array from discontinued contact pin technologies onto a modern inkjet microarrayer – dramatically improving speed, accuracy, density and spot morphology.

Other examples include a protein–peptide array for profiling the COVID-19 humoral response, and our work with KEMRI-Wellcome Trust to “miniaturize” their ELISA for efficient malaria vaccine target identification, which increased its productivity by 99%.

SW: How do these more modern, advanced microarrays compare to other high-throughput technologies? Can they help to address the increasing demand for high-throughput screening?

IM: There are many approaches to high-throughput screening including cell-based assays, multiplexing with beads, RNA sequencing and mass spectrometry. Microarrays are an established, well-validated technique capable of complementing and augmenting these approaches.

Not just for DNA, microarrays can screen a wide range of biochemical samples – and inkjet microarrays do this simply, reliably and quickly. As an example of throughput, an Arrayjet Mercury microarrayer:

• Deposits over 700 features per second
• Can load over 18,000 samples in a single batch
• Prints up to 1,000 slides in a single batch
• Needs just 0.5 µl of each sample for 1000 slides
• Can fit 100,000 features onto each microscope slide

With inkjet technology, Arrayjet’s microarray instruments and services are well-equipped to meet industry demands for cost-effective, high-quality and high-throughput screening.

Dr. Iain McWilliam was speaking to Sarah Whelan, Science Writer for Technology Networks.