Small, But Mighty

Picture a laboratory and many of us get the same image: a set of benchtops crowded with equipment from thermocyclers to hot plates. Dominating the scene is the king of the lab, a large microscope with a bulky stage, illuminator, and perhaps even a computer or digital camera attachment. We’ve all seen – probably even worked in – laboratories just like this. But this kind of setup doesn’t work for everyone, especially pathologists who are “on the road” teaching, training, or working in remote field environments. Those pathologists need an entirely different kind of microscope – but unfortunately, their options to date have not been great. Portable microscopes usually mean a compromise on image quality, whereas the instruments that could provide the detail and resolution needed for definitive diagnosis are too large, sensitive, and resource-intensive for field use. It’s clear that we need a better solution – and that’s where I hope our new take on field microscopy comes in.

We have developed the ioLight microscope (iolight.co.uk), which is small enough to fit in a jacket pocket, yet produces images that we believe are comparable with the ones from a full-size laboratory microscope. The microscope unfolds for use, so when it’s in its working position, the optical head that houses the lens and camera is rigidly supported over the stage and the bottom illuminator. The optical system uses mobile phone components to keep the cost down – and thanks to the quality of modern mobile phone parts and the microscope’s careful design, ioLight can achieve 1 μm resolution.

It started with a casual conversation…

My co-founder Richard Williams and I are experienced entrepreneurs and have been involved in a number of startup ventures together. At the beginning of 2013, we sat in a pub together, wondering what to do next. All the best startups are based on a change in the market, and we were excited by the fabulous quality of the latest tablet and mobile phone displays. How could we best take advantage of that to create new and useful technologies? We considered cameras and endoscopes, but ultimately, we decided that there were already enough good – and widely available – examples of those tools. That’s when we noticed that the only microscopes available were low resolution, poor quality, or needed a separate stand and illuminator to produce great images, which meant that they weren’t really portable.

From our optics experience, we knew we needed a microscope with a proper stage to hold the sample still; otherwise, there was no way to get a resolution better than 1μm. The stage needed two illuminators: one to light biological samples from below, and a top illuminator for opaque samples. It also needed an optical system that was easy to set up well. Laboratory microscopes are quite complicated to set up properly, but we wanted ours to be a device that anyone could use in the field, even if they had no special training.

Conventional optical microscopes are rigid and robust. They produce great images, but they’re heavy and tall, so they’re very difficult to move around. You also need to add an expensive camera to record images onto a computer, which makes the system even less portable. Digital microscopes are a little different; inexpensive ones are easy to obtain – you can even find them on Amazon – and are great for looking at big subjects like bugs and skin lesions, but not well suited to smaller things. Why? Conventional digital microscopes are handheld, and you can’t hold your hand still enough for 1 μm resolution. Adding a stand makes the microscope just as bulky and inconvenient as an optical microscope, and if you then tack on a stage to hold the sample still and an illuminator to light it correctly, you’ve got a device that’s anything but portable. Our aim was to fill the gap by developing something that was small enough to be handheld, but could image subjects right down to the size of a single cell – and we managed to achieve it (see Figure 1).

Challenging conventions

While we were working to develop the prototype, the biggest problem we encountered was how to design a flat, pocket-sized microscope with its optical head suspended rigidly above a stage. Several designs and experiments showed that the microscope had to fold, which clearly goes against years of experience indicating that microscopes have to be very rigid to deliver high-resolution images. Previous successful optical field microscopes like the McArthur and the Lensman are rugged, monolithic devices that produce good images in all climates – but we were aiming for something different. We wanted a device that didn’t have to be held up to the eye for viewing (making it difficult to manipulate the slide), didn’t require a tripod, and incorporated image and video capture directly into the device instead of requiring a separate camera. This research led to ioLight’s patent application for a high-resolution, portable digital microscope.

We particularly wanted our microscope to be wireless. Nobody wants to carry wires in the field – and nowadays, everything is wireless! The problem with that, though, was that we also wanted high-definition video – and to make it harder still, we wanted zero delay in the wireless video, because focusing a microscope with a two-second delay (standard on most wireless video systems) would be very frustrating! It turns out that this is quite a difficult combination to achieve. We had to engage an expert software team to help, but in the end, we managed to create exactly what we wanted: a microscope with no wires, no delays, and no penalties paid in the form of video quality.

How does it work? Once the microscope is turned on and its mast unfolded, it creates its own Wi-Fi network to connect to the user’s iPad, where the ioLight app is installed. The user can then place a slide or sample on the stage over the bottom illuminator. Coarse focus is achieved by manually adjusting the microscope’s camera head; fine focus adjustments use a digital slider in the iPad app. The app also controls illumination, letting the user adjust both top and bottom illuminators on a brightness scale from 0 to 4. Once the image looks right, simply capture a still photograph or video using the app – it’s stored directly in the iPad’s gallery for record-keeping or sharing for long-distance consultation.

The world in your pocket

We expect the new microscope to change the day-to-day work of any professional involved in education or outreach. It’s easy to use and travel with, and it can send images to mobile devices in real-time, so that a group of people can review and discuss an image at the same time. The utility of a function like that as a teaching tool is clear – and not just for training early-career pathologists, but even for non-scientists. Young people, for instance, associate more closely with phones and tablets than they do with traditional microscopes, and we’ve had great success with children as young as eight. It might not seem relevant to pathology at first glance – but this kind of engagement is vital in getting young people interested in pathology without letting the specter of the old, clunky microscope get in the way.

In the clinical setting, the microscope is great for explaining diagnoses to patients. Biopsies can be checked quickly while the patient is present, allowing them to be reassured on the spot, or letting doctors decide when to prioritize further analysis of a sample. In remote clinics, a portable device like this is useful, not just because you can take it anywhere, but because once you’ve captured an image, you can share it immediately with colleagues anywhere in the world for an expert opinion that might not be available on the ground. I believe that this will be a particularly important application in developing countries where resources are limited. Where power can be intermittent, the ioLight has another advantage: it can run for four hours or more on its internal battery and additional battery power can be provided by a standard external USB power pack. One day, perhaps, pathologists will carry such microscopes all over the world to provide quick, expert diagnoses in the unlikeliest of places.

Of course, that won’t happen immediately. We’ve just this month started manufacture of the microscope, but we’re looking forward to evaluating it for clinical use soon. It has already been evaluated for white blood cell counting using a Neubauer chamber. At the moment, we’re also working with a pathologist who is using our prototype in outreach applications like a “Colorful Pathology” display in local public science shows. 
Although the real test of the new device’s utility will come with a move to full-time clinic use, so far, reactions to it indicate that a high-resolution, portable digital pocket microscope is exactly the tool many pathologists and laboratory scientists have been waiting for!

Andrew Monk is a co-founder of ioLight Limited.