Single-cell level protein analysis utilizing mass spectrometry (MS) with picolitre sample volumes needs sensitivity in the range of zeptomole to attomole. An article published recently in the journal Analytical Chemistry discussed an analytical pretreatment method based on a nanofluidic device to downsize the chemical unit operations to the range of femtoliter to picolitre volume in mass spectrometry.
Although mass spectrometry has achieved ultra-high sensitivity detection, preventing sample loss and interfacing between femtolitre to picolitre volumes for pretreatment remains a challenging issue. In this study, the researchers utilized a nanofluidic device to achieve a high-sensitivity detection at the MS interface. Followed by charging analyte molecules by the electrodes, the nanofluidic device helped in the conversion of liquid samples to femtoliter droplets.
After the generation of droplets by a nanofluidic device, an inertial force acted on the sample femtoliter volumed droplet to carry it with a controlled trajectory. Finally, the droplet gets injected into the mass spectrometer instrument. A module was designed and constructed for heat transfer which vaporized all the injected droplets into gas-phase ions. Detecting caffeine ions utilizing the designed MS interface based on a nanofluidic device showed a limit of detection (LOD) of 1.52 attomole.
Compared to the conventional mass spectrometry interface that utilizes electrospray ionization, the present interface based on a nanofluidic device achieved 290 times higher efficiency. Moreover, a 100% sample injection rate was achieved through the nanofluidic method, which resulted in a two-fold higher sensitivity. Thus, the developed methodology based on a nanofluidic device facilitated the analysis of samples in ultrasmall quantities with high sensitivity.
Mass Spectrometry Interface for High Detection Sensitivity
Nanofluidic studies fabricate nanofluidic devices or nanopatterning to achieve a small size. It can achieve nanofluidic manipulation for biological structures and nanoparticles at a nanoscale level. MS-based protein analysis at the single-cell level helps elucidate disease mechanisms and cellular expressions.
Nevertheless, these protein analysis processes need the integration of a pretreatment based on a nanofluidic device to prepare ultrasmall sample volumes before their introduction into a mass spectrometer to facilitate dispersion and prevent sample loss. While microfluidics allows chemical operations in 10 to 100 micromolar spaces, nanofluidics exploits 100−1000 nanomolar spaces with femtolitre to picolitre volumes.
Electrospray ionization (ESI) is a widely used MS interface, which involves applying high voltage to a liquid sample followed by spraying the sample through a capillary, via the electrical repulsive force for ionization. Thus, the sample dispersion by spraying caused by ESI reduces the rate of sample injection into the mass spectrometer, consequently reducing the sensitivity. To this end, nanoESI had reduced capillary size and was extensively used for enhanced sensitivity.
Moreover, MS interfaces utilizing ultrasonic waves and laser ablation to vaporize and eject liquid samples were reported. The piezoelectric interface is another method that shoots sample droplets like an inkjet printer. However, droplets of nanoliter volume are too large to produce gas-phase ions by vaporizing the sample solution.
Femtoliter-droplet MS Interface Utilizing Nanofluidic Device
In their previous work, the team developed a microfluidic device, which utilized a two-step airflow to convert the liquid sample into uniform droplets, followed by their ejection into the air with a controlled trajectory. The droplets generated in this study were of volume between 4 and 25 picolitres. However, this volume range was too large for vaporization.
In the present study, an MS interface based on a nanofluidic device was developed to generate ultrasmall droplets and achieve high-sensitivity analyses, wherein femtoliter-droplet shooter was utilized without sample dispersion. An analytical system was developed with a nanofluidic device integrated MS interface based on a single quadrupole mass spectrometer to prove this principle.
Through the MS interface, which was based on a nanofluidic device, femtoliter droplets were generated. The force that acted on the generated sample droplets carried them with a controlled trajectory and injected them into a mass spectrometer with 100% efficiency. Later, the constructed heat transfer module vaporized the droplets to produce gas-phase ions.
The constructed MS system integrated with an MS interface based on a nanofluidic device helped evaluate the MS detection sensitivity. Results were compared to that of conventional ESI-MS. The results confirmed that the constructed MS interface based on a nanofluidic device detected ultrasmall samples with ultrahigh sensitivity.
What Did the Study Find?
To summarize, the nanofluidic device-based MS interface method was developed to generate femtoliter droplets, which were ejected with a controlled trajectory to achieve high-sensitivity detection. Furthermore, the heat transfer thermal system achieved 100% vaporization of droplets injected into MS’s aperture.
The voltage applied increased the charge imposition efficiency in the sample liquid and the results revealed that the MS interface based on a nanofluidic device achieved high-sensitive MS detection. The ionized caffeine showed 290 times higher sensitivity of detection than conventional ESI due to the achieved femtoliter droplet via MS interface based on a nanofluidic device.
News
UCLA Scientists Uncover a “Hidden Weakness” in Some of the World’s Deadliest Cancers
A new study has uncovered an unexpected vulnerability in some of the deadliest cancers. Researchers at UCLA have identified a previously hidden weakness in some of the most aggressive cancers, pointing to a possible new way [...]
AI-designed universal coronavirus vaccine clears first human trial
Key Takeaways Super-Antigen Technology: Uses AI and machine learning to analyze viral genomes, creating a single vaccine that targets essential features across entire virus families, including coronaviruses and Ebola. Human Trials & Safety: Phase [...]
Researchers Discover a Hidden Vitamin D Problem That Persists Year-Round
A new study suggests that some groups may not experience the expected seasonal boost in vitamin D levels, even during the sunniest months of the year. Many people assume that spending more time outdoors [...]
Researchers Solve the Mystery Behind a Billion-Dollar Dental Implant Disease
Researchers have uncovered why a common and costly dental implant infection often resists antibiotics. Dental implants have helped tens of millions of people regain a full set of stable, functional teeth, something traditional dentures [...]
Nanoparticles inspired by lung fluid improve therapies targeting respiratory system
The CIC biomaGUNE Center for Cooperative Research in Biomaterials has developed pulmonary surfactant nanoparticles (the blend of lipids and proteins that line the alveoli and enables breathing), which are encapsulated [...]
Scientists Finally Uncover How a “Forever Chemical” Causes Birth Defects
PFDA, a PFAS “forever chemical,” can cause craniofacial birth defects by disrupting retinoic acid regulation during fetal development, revealing the first clear molecular mechanism behind the link. Researchers have long linked perfluoroalkyl and polyfluoroalkyl substances (PFAS), [...]
Scientists Have Discovered These Deadly Parasites Are Secretly Swapping DNA
Leishmania parasites appear to evolve through widespread genetic exchange, reshaping assumptions about how they adapt and spread. A parasite long thought to spread mostly by cloning itself may be far more genetically dynamic than [...]
Stanford’s Revolutionary New Microscope Reveals Living Cells in Stunning Detail
Stanford researchers have developed a microscope that can show how nanostructures interact inside living cells at the highest resolution achieved so far. The view into living cells just got better. Stanford researchers have merged [...]
What Bundibugyo Ebola vaccines and treatments are under development
By Mariam Sunny and Jennifer Rigby May 29 (Reuters) – Global health authorities are racing to identify medical options to help contain an Ebola outbreak in eastern Democratic Republic of Congo, linked to the [...]
Why More People in Their 30s Are Suddenly Getting Colon Cancer
A major Swiss study found that colorectal cancer is becoming increasingly common in adults under 50, even as rates decline in older age groups. Researchers in Switzerland have identified a concerning trend: while colorectal [...]
Researchers Compare MS Models to Human Tissue in Search for Better Therapies
Researchers identified key differences between two widely used multiple sclerosis models, showing how each can better study myelin damage, immune responses, and repair. The findings may improve efforts to develop treatments that restore lost [...]
Scientists Discover Genetic “Off Switch” That Supercharges CAR T Cells Against Cancer
A new study reveals a possible way to make CAR T-cell therapy more durable and effective by targeting a single gene-regulating protein. CAR T-cell therapy is widely seen as a breakthrough in personalized cancer [...]
New Vitamin B12-Based Therapy Could Change How Brain Cancer Is Treated
Researchers have identified a vitamin B12–based compound that appears capable of crossing the blood–brain barrier and selectively accumulating in glioblastoma tissue. For decades, one of the biggest problems in brain cancer treatment has had [...]
Simple Fiber Supplement Cuts Knee Arthritis Pain in Just 6 Weeks, Study Finds
A daily inulin supplement may help reduce knee osteoarthritis pain while revealing a possible link between gut health, muscle function, and pain sensitivity. For millions of people living with knee osteoarthritis, managing chronic pain [...]
This Common Vitamin May Help Stop Prediabetes From Turning Into Diabetes
Vitamin D may help prevent type 2 diabetes in people with specific genetic variations, offering a possible path toward personalized diabetes prevention. More than 40% of U.S. adults have prediabetes, a condition in which [...]
Ebola, hantavirus: Is the world prepared for the next pandemic?
Funding cuts to health research and a growing antivaccine movement are making it harder than ever to respond to viruses. The World Health Organization (WHO) has declared that an Ebola outbreak in Uganda and [...]
