Researchers 3D print key components for a point-of-care mass spectrometer
MIT researchers have 3D print­ed a minia­ture ion­iz­er, which is a key com­po­nent of a mass spec­trom­e­ter. The new minia­ture ion­iz­er could some­day enable an afford­able, in-home mass spec­trom­e­ter for health mon­i­tor­ing. Pic­tured are parts of the new device, includ­ing a green print­ed cir­cuit board (PCB) with orange cas­ing on top. Under the cas­ing is a black rec­tan­gle where the elec­tro­spray emit­ter is locat­ed. Cred­it: Mass­a­chu­setts Insti­tute of Tech­nol­o­gy

Mass spec­trom­e­try, a tech­nique that can pre­cise­ly iden­ti­fy the chem­i­cal com­po­nents of a sam­ple, could be used to mon­i­tor the health of peo­ple who suf­fer from chron­ic ill­ness­es. For instance, a mass spec­trom­e­ter can mea­sure hor­mone lev­els in the blood of some­one with hypothy­roidism.

But mass spec­trom­e­ters can cost sev­er­al hun­dred thou­sand dol­lars, so these expen­sive machines are typ­i­cal­ly con­fined to lab­o­ra­to­ries where blood sam­ples must be sent for test­ing. This inef­fi­cient process can make man­ag­ing a chron­ic dis­ease espe­cial­ly chal­leng­ing.

“Our big vision is to make mass spec­trom­e­try local. For some­one who has a chron­ic dis­ease that requires con­stant mon­i­tor­ing, they could have some­thing the size of a shoe­box that they could use to do this test at home. For that to hap­pen, the hard­ware has to be inex­pen­sive,” says Luis Fer­nan­do Velásquez-Gar­cía, a prin­ci­pal research sci­en­tist in MIT’s Microsys­tems Tech­nol­o­gy Lab­o­ra­to­ries (MTL).

He and his col­lab­o­ra­tors have tak­en a big step in that direc­tion by 3D print­ing a low-cost ionizer—a crit­i­cal com­po­nent of all mass spectrometers—that per­forms twice as well as its state-of-the-art coun­ter­parts.

Their device, which is only a few cen­time­ters in size, can be man­u­fac­tured at scale in batch­es and then incor­po­rat­ed into a mass spec­trom­e­ter using effi­cient, pick-and-place robot­ic assem­bly meth­ods. Such mass pro­duc­tion would make it cheap­er than typ­i­cal ion­iz­ers that often require man­u­al labor, need expen­sive hard­ware to inter­face with the mass spec­trom­e­ter, or must be built in a semi­con­duc­tor clean room.

By 3D print­ing the device instead, the researchers were able to pre­cise­ly con­trol its shape and uti­lize spe­cial mate­ri­als that helped boost its per­for­mance.

“This is a do-it-your­self approach to mak­ing an ion­iz­er, but it is not a con­trap­tion held togeth­er with duct tape or a poor man’s ver­sion of the device. At the end of the day, it works bet­ter than devices made using expen­sive process­es and spe­cial­ized instru­ments, and any­one can be empow­ered to make it,” says Velásquez-Gar­cía, senior author of a paper on the ion­iz­er pub­lished in Jour­nal of the Amer­i­can Soci­ety for Mass Spec­trom­e­try. He wrote the paper with lead author Alex Kachkine, a mechan­i­cal engi­neer­ing grad­u­ate stu­dent.

Low-cost hardware

Mass spec­trom­e­ters iden­ti­fy the con­tents of a sam­ple by sort­ing charged par­ti­cles, called ions, based on their mass-to-charge ratio. Since mol­e­cules in blood don’t have an elec­tric charge, an ion­iz­er is used to give them a charge before they are ana­lyzed.

Most liq­uid ion­iz­ers do this using elec­tro­spray, which involves apply­ing a high volt­age to a liq­uid sam­ple and then fir­ing a thin jet of charged par­ti­cles into the mass spec­trom­e­ter. The more ion­ized par­ti­cles in the spray, the more accu­rate the mea­sure­ments will be.

The MIT researchers used 3D print­ing, along with some clever opti­miza­tions, to pro­duce a low-cost elec­tro­spray emit­ter that out­per­formed state-of-the-art mass spec­trom­e­try ion­iz­er ver­sions.

They fab­ri­cat­ed the emit­ter from met­al using binder jet­ting, a 3D print­ing process in which a blan­ket of pow­dered mate­r­i­al is show­ered with a poly­mer-based glue squirt­ed through tiny noz­zles to build an object lay­er by lay­er. The fin­ished object is heat­ed in an oven to evap­o­rate the glue and then con­sol­i­date the object from a bed of pow­der that sur­rounds it.

“The process sounds com­pli­cat­ed, but it is one of the orig­i­nal 3D print­ing meth­ods, and it is high­ly pre­cise and very effec­tive,” Velásquez-Gar­cía says.

Then, the print­ed emit­ters under­go an elec­trop­o­l­ish­ing step that sharp­ens it. Final­ly, each device is coat­ed in zinc oxide nanowires which give the emit­ter a lev­el of poros­i­ty that enables it to effec­tive­ly fil­ter and trans­port liq­uids.

Researchers 3D print key components for a point-of-care mass spectrometer
Researchers designed elec­tro­spray emit­ters as exter­nal­ly-fed sol­id cones with a spe­cif­ic angle that lever­ages evap­o­ra­tion to strate­gi­cal­ly restrict the flow of liq­uid. Pic­tured are some pho­tos and illus­tra­tions of the device. Cred­it: Mass­a­chu­setts Insti­tute of Tech­nol­o­gy

Think­ing out­side the box

One pos­si­ble prob­lem that impacts elec­tro­spray emit­ters is the evap­o­ra­tion that can occur to the liq­uid sam­ple dur­ing oper­a­tion. The sol­vent might vapor­ize and clog the emit­ter, so engi­neers typ­i­cal­ly design emit­ters to lim­it evap­o­ra­tion.

Through mod­el­ing con­firmed by exper­i­ments, the MIT team real­ized they could use evap­o­ra­tion to their advan­tage. They designed the emit­ters as exter­nal­ly-fed sol­id cones with a spe­cif­ic angle that lever­ages evap­o­ra­tion to strate­gi­cal­ly restrict the flow of liq­uid. In this way, the sam­ple spray con­tains a high­er ratio of charge-car­ry­ing mol­e­cules.

“We saw that evap­o­ra­tion can actu­al­ly be a design knob that can help you opti­mize the per­for­mance,” he says.

They also rethought the counter-elec­trode that applies volt­age to the sam­ple. The team opti­mized its size and shape, using the same binder jet­ting method, so the elec­trode pre­vents arc­ing. Arc­ing, which occurs when elec­tri­cal cur­rent jumps a gap between two elec­trodes, can dam­age elec­trodes or cause over­heat­ing.

Because their elec­trode is not prone to arc­ing, they can safe­ly increase the applied volt­age, which results in more ion­ized mol­e­cules and bet­ter per­for­mance.

They also cre­at­ed a low-cost, print­ed cir­cuit board with built-in dig­i­tal microflu­idics, which the emit­ter is sol­dered to. The addi­tion of dig­i­tal microflu­idics enables the ion­iz­er to effi­cient­ly trans­port droplets of liq­uid.

Tak­en togeth­er, these opti­miza­tions enabled an elec­tro­spray emit­ter that could oper­ate at a volt­age 24% high­er than state-of-the-art ver­sions. This high­er volt­age enabled their device to more than dou­ble the sig­nal-to-noise ratio.

In addi­tion, their batch pro­cess­ing tech­nique could be imple­ment­ed at scale, which would sig­nif­i­cant­ly low­er the cost of each emit­ter and go a long way toward mak­ing a point-of-care mass spec­trom­e­ter an afford­able real­i­ty.

“Going back to Gut­ten­berg, once peo­ple had the abil­i­ty to print their own things, the world changed com­plete­ly. In a sense, this could be more of the same. We can give peo­ple the pow­er to cre­ate the hard­ware they need in their dai­ly lives,” he says.

Mov­ing for­ward, the team wants to cre­ate a pro­to­type that com­bines their ion­iz­er with a 3D-print­ed mass fil­ter they pre­vi­ous­ly devel­oped. The ion­iz­er and mass fil­ter are the key com­po­nents of the device. They are also work­ing to per­fect 3D-print­ed vac­u­um pumps, which remain a major hur­dle to print­ing an entire com­pact mass spec­trom­e­ter.

“Minia­tur­iza­tion through advanced tech­nol­o­gy is slow­ly but sure­ly trans­form­ing mass spec­trom­e­try, reduc­ing man­u­fac­tur­ing cost and increas­ing the range of appli­ca­tions. This work on fab­ri­cat­ing elec­tro­spray sources by 3D print­ing also enhances sig­nal strength, increas­ing sen­si­tiv­i­ty and sig­nal-to-noise ratio and poten­tial­ly open­ing the way to more wide­spread use in clin­i­cal diag­no­sis,” says Richard Syms, pro­fes­sor of microsys­tems tech­nol­o­gy in the Depart­ment of Elec­tri­cal and Elec­tron­ic Engi­neer­ing at Impe­r­i­al Col­lege Lon­don, who was not involved with this research.


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