Oftentimes, people avoid their annual visits to the doctor or semi-annual visits to the dentist in a bid to avoid potential pain — typically inflicted by needles or other tools necessary to a procedure. But what if that pain could be alleviated or even eliminated altogether?

That is the aim, in part, for a number of researchers from across the globe who are exploring avenues ranging from painlessly diagnosing skin cancer to painlessly administering vaccines — all in the name of preventing pain.

Follow along with GlobalSpec as we review some of the technologies designed to take the sting out of healthcare.

Painless skin cancer detection

A new painless approach for detecting malignant melanoma — which is a type of skin cancer — has been developed by researchers from Sweden’s Karolinska Institutet.

According to the researchers, the painless approach includes a patch outfitted with microneedles capable of detecting tyrosinase — an enzyme that is a biomarker for malignant melanoma — directly in the skin.

Using the microneedle patch to painlessly measure the enzyme's levels directly in the skin will reportedly enable healthcare workers to quickly identify changes linked to the disease, the researchers explained.

Illustration of smart probe modified epidermal microneedle sensor patch. Representative demonstration of skin melanosis on the back of the female patient. Source: Advanced Materials (2024). DOI: 10.1002/adma.202403758

Painless therapeutic drug monitoring

Researchers from the Division of Internal Medicine, University Hospital Basel, Basel, Switzerland, are suggesting that exhaled breath could be a painless alternative to drawing blood for the therapeutic monitoring (TDM) of antibiotics.

TDM is often used to monitor antibiotic concentrations in patients with severe infections and in those in intensive care units to ensure they are receiving the appropriate dosage of antibiotics based on their needs — for instance, patients might metabolize drugs differently and consequently not respond to conventional doses of antibiotics, perhaps requiring higher or lower doses.

Traditionally, TDM is performed using blood collection methods that tend to be painful and invasive as well as time- and resource-consuming, often taking several hours and even days to get results.

As such, the team is examining whether exhaled breath might be a painless and suitable alternative, citing that the process is non-invasive and that breath when combined with real-time analyses, potentially offers results in roughly 10 minutes in some cases.

To test this approach, the team conducted a study with 10 patients who had received intravenous antibiotic treatment in 2022 or 2023. The patients were being treated for: respiratory infections (n=3), intravascular infections (n=3), abdominal infections (n=2), urinary tract infection (n=1) or skin and soft tissue infection (n=1) with meropenem (n=3), piperacillin/tazobactam (n=3), cefazolin (n=2), flucloxacillin (n=1) or ciprofloxacin (n=1).

To analyze samples of exhaled breath for exogeneous and endogenous metabolites — which are, respectively, the breakdown products of the antibiotic and breakdown products from the body affected by the antibiotic — the team employed mass spectrometry.

For the antibiotics meropenem, cefazolin, flucloxacillin and ciprofloxacin, it was possible to detect differences in the levels of specific metabolites while with the antibiotic piperacillin/tazobactam there was no clear, detectable signal.

Painless blood draw

Taking inspiration from leeches, a device that painlessly draws blood without large needles has been developed by a team of scientists from ETH Zurich.

To painlessly and accurately draw blood samples, the device uses a combination of microneedles and a suction cup.

Much like leeches — which attach themselves to the host’s skin and suck blood with their teeth from the wounded area, subsequently creating negative pressure by swallowing — the 2.5 cm long silicone suction cup component of the device is affixed to the arm or back of a patient. Within that suction cup are a series of steel microneedles that puncture the skin when the device is pushed.

Within just minutes, negative pressure within the suction cup ensures that an appropriate amount of blood can be collected for diagnostic testing, the device's developers explained.

Painless drug delivery

Taking inspiration from the blue-ringed octopus, which punctures the shell of crustaceans to deliver the paralyzing agent tetrodotoxin to its prey, a group of scientists from various universities in China has developed a microneedle-based patch that adheres to the surface of skin and delivers drugs.

To mimic the mechanism used by the blue-ringed octopus, the team designed a patch featuring hydrogel suction cups and microneedles composed of silk fibroin and F127 hydrogel.

According to the researchers, the microneedles are reportedly heat sensitive, thereby enabling improved control for drug release.

In the lab, the patch was applied to areas within the mouths of animals inflamed with gum ulcers or superficial tumors. The team discovered that the suction cups worked as intended as the teeth on the patch enabled the ideal amount of surface puncture for the delivery of medications. Further, the microneedles also reportedly delivered the medication within two hours of application.

After two days, the patches also delivered the desired amount of medication, while over time, the patch increased the healing speed of the ulcers and prevented tumor growth.

Painless vaccine delivery

Scientists from Stanford University and the University of North Carolina at Chapel Hill have developed a 3D-printed patch for painlessly delivering the COVID-19 vaccine.

Source: University of North Carolina at Chapel Hill

The 3D-printed polymer patch, which features an array of microneedles, delivered an immune response 10 times that of vaccines delivered via syringe in the lab, according to the researchers. Reportedly, the patch produced a T-cell and antigen-specific antibody response 50 times greater than that administered via subcutaneous injection.

Consequently, the team believes that the patch, which delivers smaller doses of the vaccine, could potentially encourage dose sparing, delivering a similar immune response using less.

Painless treatment of diabetic ulcers

A microneedle array that successfully penetrates the biofilms that commonly form over the ulcerated tissues and cells associated with diabetic foot ulcers to deliver antibiotics to the wounds has been developed by engineers from Indiana’s Purdue University.

According to the engineers, the microneedle array punctures the seemingly impenetrable shield of biofilm that forms on non-healing, chronic wounds to absorb the liquid beneath the biofilm and then dissolves it. This enables both oxygen and bactericidal agents to reach and treat the wounds.

Likewise, the patent-pending microneedle array is reportedly painless, due to microneedles not being long enough to touch nerve endings in the foot. This is unlike previous methods for bypassing biofilm, which included peeling it off — an approach that is both painful and that does not distinguish between unhealthy and healthy tissue.

Source: Purdue University

Painless antibiotic delivery

Researchers at Karolinska Institutet in Sweden have developed a micro-needle patch for the painless, local delivery of antibiotics for treating methicillin-resistant Staphylococcus aureus, better known as MRSA, skin infections.

The microneedle patch features a series of mini polymer needles loaded with vancomycin, an antibiotic used to clear up bacterial infections.

The microneedles are so small that they do not reach the pain receptors, making the treatment relatively painless. Source: Jill Ziesmer, Karolinska Institutet

Current methods for treating MRSA skin infections include intravenous injections of vancomycin. According to researchers, vancomycin could not previously be given locally due to its inability to penetrate the skin. Even when higher doses of vancomycin were administered, penetration was still inefficient, and the higher doses threatened to result in the development of antibiotic-resistant strains. Likewise, the antibiotic is not administered orally due to poor gut absorption.

Conversely, the microneedle patch design allows for the controlled and painless delivery of vancomycin directly at the site of the skin infection.